2015 UTI Complicated PDF

Philippine Clinical Practice
Guidelines on the Diagnosis and

Management of Urinary Tract
Infections in Adults
2013 Update
(Part 1)
O BI O L O G Y
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9 70 AD-
This guideline is intended for use by a broad range of health care
professionals, including general practitioners, medical specialists,
administrators, policy makers and nurses.
Suggested Citation
Task Force on UTI 2013, Philippine Practice Guidelines Group in

Infectious Diseases. Urinary Tract Infections in Adults 2013 Update.
PPGG-ID Philippine Society for Microbiology and Infectious Diseases
Volume ___ No ___ Quezon City, Philippines. Copyright PSMID 2013
ISBN ______
Philippine Clinical Practice Guidelines
on the Diagnosis and Management
of Urinary Tract Infections in Adults
2013 Update
Part 1
Uncomplicated Urinary Tract Infections

Urinary Tract Infections in Pregnancy
blank
Task Force Members
Organizations: PSMID, POGS, PSN, PUA, PAFP

Chair: Mediadora C. Saniel
Co-chair: Marissa M. Alejandria
Uncomplicated Urinary Tract Infection Cluster

Thea C. Patino (Head)
Evalyn A. Roxas (Head)
Karen Marie R. Gregorio
Annabelle M. Laranjo
Kathryn U. Roa
Rommel P. Sumilong
Anna Marie S. Velasco
Rosally P. Zamora
Urinary Tract Infection in Pregnancy and Asymptomatic Bacteriuria in

Adults Cluster
Ricardo M. Manalastas Jr. (Head)
Louella P. Aquino
Shahreza L. Baquiran
Sybil Lizzane R. Bravo
Jennifer T. Co
Maria Meden P. Cortero
Lorina Q. Esteban
Analyn F. Fallarme
May Gabaldon
Jill R. Itable
Alfredo M. Lopez, Jr
Helen V. Madamba
Josefa Dawn V. Martin
Erwin R. De Mesa
Sharon Faith B. Pagunsan
Oliver S. Sanchez
Katha W. Ngo-Sanchez
Research Associates: Richelle G. Duque

Grace Kathleen T. Serrano
Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1 i

Table of Contents
Introduction ....................................................................................... 1
Methodology ..................................................................................... 1
Acute Uncomplicated Urinary Tract Infections.................................. 5
Acute Uncomplicated Cystitis In Women.......................................... 7
Acute Uncomplicated Pyelonephritis In Women............................... 24
Urinary Tract Infections In Pregnancy .............................................. 43
Asymptomatic Bacteriuria In Pregnancy........................................... 45
Acute Cystitis In Pregnancy.............................................................. 57
Acute Uncomplicated Pyelonephritis In Pregnancy .......................... 65
Acknowledgement ............................................................................ 74
List of Tables
Table 1. Strength of Recommendation and Quality of Evidence ......... 2
Table 2. Conditions that define complicated UTI ............................ 9
Table 3. Accuracy of clinical signs and symptoms
in the prediction of UTI ..................................................... 11
Table 4. Antibiotics that can be used for AUC ................................ 13
Table 5. Percent Resistance of Urinary E.coli (outpatient
urine specimens) .............................................................. 14
Table 6. Empiric treatment regimens for acute
uncomplicated pyelonephritis ........................................... 31
Table 7. Computed Likelihood Ratios for the different
screening tests compared with urine culture .................... 50
Table 8. Antibiotics that can be used for asymptomatic
bacteriuria in pregnancy ................................................... 54
Table 9. Antibiotics that can be used for acute cystitis
in pregnancy ..................................................................... 61
Table 10. Empiric treatment regimens for acute uncomplicated
pyelonephritis in pregnant women .................................... 71
List of Algorithms
Algorithm 1. Evaluating a Woman with Symptoms of Acute
Urinary Tract Infection ............................................ 4
Algorithm 2. Management of Acute Uncomplicated Cystitis....... 21
Algorithm 3. Treatment of acute uncomplicated
pyelonephritis in non-pregnant women .................. 39
Algorithm 4. Alternative diagnostic evaluation for
asymptomatic bacteriuria in settings where
urine culture is not available .................................. 55
ii Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

INTRODUCTION
Urinary tract infections (UTI) were among the leading indications for
seeking healthcare and using antimicrobials in the community and
hospital settings. The Philippine Clinical Practice Guidelines on the
Diagnosis and Management of Urinary Tract Infections in Adults were
fi st p lished in and e ised in to p o ide p ima ca e
ph sicians and specialists ith e idence ased ecommendations
on the care of patients with UTI. The current guidelines further
pdated the ecommendations ollo in an e tensi e e ie o mo e
ecent lite at e This as the fi st time that the adin
o ecommendations ssessment e elopment and al ation
s stem as sed to de elop idelines in in ectio s diseases in the
country. The outputs were consensus recommendations of a panel
o clinicians con ened the hilippine ociet o ic o iolo
and In ectio s iseases I in colla o ation ith the hilippine
stet ic and necolo ical ociet hilippine ociet o
eph olo hilippine cadem o amil h sicians
and Philippine Urological Association (PUA).
The oc s o the idelines as on dia nosis t eatment and

p e ention o UTI in ad lts and consists o t o pa ts
Part One – Acute Uncomplicated UTI and UTI in Pregnancy
atT o s mptomatic acte i ia ec ent UTI and
Complicated UTI
In formulating optimal approaches to the care of both outpatients

and inpatients ith UTI the panel conside ed se e al iss es elated
to chan in p e alence and esistance patte ns o opatho ens
a aila ilit and p actica ilit o dia nostic tests and cost e ecti eness
and ecolo ical ad e se e ects collate al dama e o t eatment
The idelines e e not intended to s pe sede a healthca e p o ide s

so nd clinical d ment a iations in clinical p esentation p esence
o como idities o a aila ilit o eso ces ma e i e adaptation
of the recommendations.
METHODOLOGY
The I in colla o ation ith and U
con ened a tas o ce o clinicians ep esentin di e ent e pe tise
incl din in ectio s diseases neph olo amil medicine o stet ics
and necolo olo and inte nal medicine The mem e s o this
tas o ce e e di ided into o cl ste s each headed a senio
specialist and se ed as the technical o in o p o o m latin
the idelines The a eas co e ed e e Cl ste ncomplicated
UTI ac te c stitis and p eloneph itis Cl ste UTI in p e nanc
and as mptomatic acte i ia Cl ste C complicated UTI and
Cluster D – recurrent UTI.
Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

ach cl ste cond cted a e ie and anal sis o the ele ant n lish
lite at e p lished since and o some topics e en ea lie
st dies The alit o the e idence as e al ated sin the
s stem as indicated in Ta le The cl ste then d a ted ideline
ecommendations and aded them as T o dependin
on the alit o the e idence alance o potential enefits and ha m
and t anslation into p actice in specific settin s and patient o ps
Th s hi h alit e idence did not necessa il constit te st on
ecommendations con e sel st on ecommendations co ld a ise
om lo alit e idence i the enefits o t ei h the ndesi a le
conse ences.
Table 1. Strength of Recommendation and Quality of Evidence1,2
Category Definition
Strength of Recommendation
Strong Desirable effects (benefits) clearly outweigh the undesirable effects
(risks)
Conditional Desirable effects probably outweigh the undesirable effects but the
recommendation is applicable only to a specific group, population,
or setting; or the benefits may not warrant the cost or resource
requirements in all settings
Weak Desirable and undesirable effects closely balanced; or uncertain, new

evidence may change the balance of risk to benefit
No recommendation Further research is required before any recommendation can be made
Quality of Evidence
High Consistent evidence from well-performed RCTs or strong evidence

from unbiased observational studies; further research is very unlikely
to change confidence in the estimate of the effect
Moderate Evidence from RCTs with important limitations or moderately strong

evidence from unbiased observational studies; further research is
likely to have an important impact on confidence in the estimate of the
effect
Low Evidence for ≥ one critical outcome from observational studies, from
RCTs with serious flaws or from indirect evidence; further research is
very likely to have an important impact in the estimate of effect and is
likely to change the estimate
Very Low Evidence for ≥ one critical outcome from unsystematic clinical
observations or very indirect evidence; any evidence of effect is very
uncertain

In addition to alit o e idence the ollo in domains e e
conside ed in adin the st en th o the ecommendations
a alance o enefits e s s ha ms and dens
al es and p e e ences Is the ecommendation li el to e
idel accepted o is the e si nificant a ia ilit o nce taint
in al es and p e e ences that the ecommendation is nli el to
be accepted?
c eso ce implications financial costs implications in ast ct e
e ipment h man eso ces e pe tise cost e ecti eness
d easi ilit Is the ecommendation achie a le in the settin
where the greatest impact is expected?
se ies o ace to ace meetin s o the tas o ce ith ep esentati es

om all o cl ste s as held to disc ss each cl ste s d a t o tp ts
The tas o ce mem e s de eloped a consens s in adin the
alit o the e idence and st en th o the ecommendations sin
the techni e Th o ho t the de elopment p ocess e pe t
ad ice on methodolo ical iss es as p o ided a tas o ce mem e
p oficient in the s stem ta les s mma i in the
alit o the e idence et ie ed e e ene ated o each ideline
estion
e ments o the idelines e e p esented in a io s o a incl din

ann al con entions o specialt societies s ch as
and I to elicit eed ac The idelines e e finali ed a te
a e mo e meetin s and e mail co espondence amon the tas
o ce mem e s and cl ste heads t e la inte als the tas
o ce leade s ill dete mine the need o e isions to the idelines
Implementation st ate ies ill also e pe iodicall e ie ed
References
att man ist n alc tte lonso Coello et al
an eme in consens s on atin alit o e idence and st en th o
ecommendations
att man n alc tte ist i e ati et al oin
om e idence to ecommendations

Algorithm 1. Evaluating a Woman with Symptoms of Acute
Urinary Tract Infection
Woman with ≥1 *dysuria, frequency, urgency, hematuria,

symptoms of UTI* discomfort in lower abdomen
es See Section on UTI in pregnancy

Pregnant?
No
Recurrent es
≥2x/year? See Section on Recurrent UTI
No
es Do urinalysis, urine culture to establish diagnosis
With risk factors for
Consider initiating empirical treatment
complicated UTI?
See Section Complicated UTI
No
Consider Acute Uncomplicated Pyelonephritis
With flank pain or es Do urinalysis, urine culture to establish diagnosis
fever? Consider empiric treatment
See Section on Acute Uncomplicated Pyelonephritis
No
Low to intermediate probability of UTI (~20%)
With vaginal es Consider Sexually Transmitted Infections
discharge? Do pelvic examination (including cervical culture when
appropriate), urinalysis, urine culture, urine Chlamydia
to establish diagnosis
No See Section on Acute Uncomplicated Cystitis
With clear history of

≥1 symptoms of UTI – es High probability of AUC (~90%)
acute onset of dysuria, Start empiric treatment without urinalysis, urine culture
frequency, urgency, See Section on Acute Uncomplicated Cystitis
hematuria?
No
Perform dipstick urinalysis
High probability of AUC (~80%)

Dipstick result es Start empiric treatment without urine culture
positive? See Section on Acute Uncomplicated Cystitis
No
Low to intermediate probability of UTI (~20%)
Consider urine culture or close clinical follow-up and pelvic examination
including cervical cultures and radiologic imaging when appropriate
See Section Uncomplicated Urinary Tract Infection

Acute uncomplicAted urinAry trAct infections
Acute Uncomplicated Cystitis
Acute Uncomplicated Pyelonephritis

ACUTE UNCOMPLICATED URINARY TRACT INFECTIONS
ACUTE UNCOMPLICATED CYSTITIS IN WOMEN
Section Summary
efinition o ac te ncomplicated c stitis UC
Clinicall UC is s spected in p emenopa sal non p e nant
omen p esentin ith ac te onset o d s ia e enc
enc and oss hemat ia and itho t a inal discha e
U inal sis is not necessa to confi m the dia nosis o UC in
omen p esentin ith one o mo e o the a o e s mptoms
o UTI in the a sence o a inal discha e and complicatin
conditions en me ated in Ta le
omen p esentin ith ina s mptoms pl s a inal discha e
sho ld nde o the e al ation
Conditions that define complicated UTI cUTI m st e a sent as
o tained on histo ta in
Strong recommendation, High quality of evidence
Approach to management
mpi ic anti iotic t eatment is the most cost e ecti e app oach
in the management of AUC.
e t eatment ine c lt e and sensiti it is T ecommended
tanda d ine mic oscop and dipstic le oc te este ase
and nit ite tests a e not p e e isites o t eatment
Antibiotic treatment
Antibiotics recommended for use in AUC are presented in Table
ficac in te ms o clinical c e cost e ecti eness sa et
and tolerability were considered in the choice of antibiotics. In
addition the p opensit to ca se collate al dama e and local
s scepti ilit ates e e i en eate ei hts in the choice o
antibiotic recommendations.
Ampicillin or amoxicillin should NOT be used for empirical

t eatment i en the elati el poo e ficac and e hi h
p e alence o antimic o ial esistance to these a ents o ld ide
T imethop im s l ametho a ole m I o th ee

da s sho ld e sed o c lt e p o en s scepti le
opatho ens d e to hi h p e alence o local esistance and
high failure rates.
it o antoin monoh d ate mac oc stals m I o fi e

da s is ecommended as the fi st line t eatment o UC d e to
its hi h e ficac minimal esistance minimal ad e se e ects lo
Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1 7

p opensit o collate al dama e and easona le cost o e e
the nit o antoin monoh d ate mac oc stal o m lation is not
locall a aila le Th s nit o antoin mac oc stal o m lation
m is ecommended t it sho ld e i en o times a da
o fi e da s
os om cin in a sin le dose is also a ecommended

anti iotic d e to its hi h e ficac con enience o a sin le dose
lo p opensit o collate al dama e ood acti it a ainst
m ltid esistant opatho ens and minimal ad e se e ects
o e e the e a e no local esistance data to date
i mecillinam m I o th ee to se en da s can e sed

in a eas he e it is a aila le as it has easona le t eatment
e ficac o e e it is not c entl a aila le in the co nt
ocal esistance data is also a sent
inolones sho ld T e sed as a fi st line d despite thei

e ficac d e to the hi h p opensit o collate al dama e
eta lactam a ents incl din amo icillin cla lanate ce aclo
ce dini ce podo ime p o etil ce ti ten and ce o ime a e
appropriate choices for therapy when other recommended
agents cannot be used.
Duration of treatment
it o antoin sho ld e i en o fi e da s hile os om cin is
i en as a sin le dose
o the alte nati e a ents
th ee da co se o o o inolone is ecommended
se en da e imen o eta lactams amo icillin
cla lanate ce aclo ce dini cefi ime ce podo ime
p o etil ce ti ten and ce o ime is ecommended
Duration of treatment for elderly women

In othe ise health elde l omen ith UC the ecommended
duration of treatment is the same as with the general population
ee Ta le
Course of action for patients who do not respond to treatment

atients hose s mptoms o sen o do not imp o e a te
completion o t eatment sho ld ha e a ine c lt e done

and antibiotic should be empirically changed pending result of
sensiti it testin
atients hose s mptoms ail to esol e a te t eatment sho ld
be managed as complicated UTI.
Strong recommendation, Low quality of evidence
ost t eatment la o ato tests

o tine post t eatment ine c lt e and inal sis in patients
hose s mptoms ha e completel esol ed a e T
ecommended as it does not p o ide an added clinical enefit
Recommendations and Summary of Evidence

1. When is AUC suspected in women?
Clinically, AUC is suspected in premenopausal non-
pregnant women presenting with acute onset of dysuria,
frequency, urgency, and gross hematuria; and without
vaginal discharge.
Urinalysis is not necessary to confirm the diagnosis of
AUC in women presenting with one or more of the above
symptoms of UTI in the absence of vaginal discharge and
Women presenting with urinary symptoms plus vaginal
discharge should undergo further evaluation.
Conditions that define complicated UTI must be absent as
obtained on history-taking.
Table 2. Conditions that define complicated UTI1–7
Presence of an indwelling urinary catheter or intermittent catheterization

Incomplete emptying of the bladder with >100 ml retained urine post-voiding
Impaired voiding due to neurogenic bladder, cystocoele
Obstructive uropathy due to bladder outlet obstruction, calculus, urethral or ureteric strictures,
tumors
Vesicoureteral reflux & other urologic abnormalities including surgically created abnormalities
Chemical or radiation injuries of the uroepithelium
Peri- or post-operative UTI
Azotemia due to intrinsic renal disease
Renal transplantation
Diabetes mellitus
Immunosuppressive conditions – e.g. febrile neutropenia, HIV-AIDS
UTI caused by unusual pathogens (M. tuberculosis, Candida spp.)
UTI caused by antibiotic-resistant or multi-drug resistant organisms (MDROs)
UTI in males except in young males presenting exclusively with lower UTI symptoms
Urosepsis

Summary of Evidence
In a ecent s stematic e ie o st dies patients
iesen et al the dia nostic acc ac o s mptoms and si ns o
ncomplicated UTI as compa ed to the old standa d ine c lt e
ac oss th ee di e ent e e ence standa ds and C U
m i s mptoms e e si nificant in dete minin the p o a ilit o
UTI The p esence o d s ia e enc enc hemat ia and
noct ia inc eased the p o a ilit o UTI ith hemat ia ha in the
hi hest dia nostic tilit ositi e li elihood atio sensiti it
confidence inte al CI specificit CI
The p esence o a inal discha e on the othe hand
decreases the probability of UTI.
n ea lie s stematic e ie ent et al also assessed the

usefulness of signs and symptoms in the diagnosis of UTI. In this
e ie the p esence o d s ia e enc hemat ia ac pain and
costo e te al tende ness inc eased the p o a ilit o UTI hile the
a sence o d s ia a sence o ac pain positi e histo o a inal
discha e positi e histo o a inal i itation and the findin o
a inal discha e on ph sical e amination dec eased the p o a ilit
of UTI.
The findin s o iesen et al e e simila to the findin s o ent

et al he e no one s mptom o si n as s ficient to ma e the
diagnosis of UTI with certainty. A combination of signs and symptoms
was needed to determine the diagnosis. The two studies differed in
that Bent et al. combined the different studies with different diagnostic
th esholds an in et een C U m and C Um hile
iesen et al anal ed the st dies ased on th ee defined dia nostic
th esholds C Um C U m and C Um

Table 3. Accuracy of clinical signs and symptoms in the prediction
of urinary tract infections*
Signs/Symptoms Summary Positive Summary Negative Summary Positive Summary

Likelihood Ratios Likelihood Ratios Likelihood Ratios Negative
(95% CI)* (95% CI)* (95% CI)† Likelihood Ratios
(95% CI) †
Dysuria 1.5 (1.2, 2.0) 0.5 (0.3, 0.7) 1.3 (1.2, 1.4) 0.5 (0.4, 0.6)
Frequency 1.8 (1.1, 3.0) 0.6 (0.4, 1.0) 1.1 (1.0, 1.2) 0.6 (0.5, 0.7)
Hematuria 2.0 (1.3, 2.9) 0.9 (0.9, 1.0) 1.7 (1.3, 2.3) 0.9 (0.8, 0.9)
Urgency - - 1.2 (1.1, 1.3) 0.7 (0.6, 0.9)
Nocturia - - 1.3 (1.1, 1.6) 0.8 (0.6, 0.9)
Fever 1.6 (1.0, 2.6) 0.9 (0.9, 1.0) 1.3 (0.6, 2.6) 1.0 (0.9, 1.0)
Flank pain 1.1 (0.9, 1.4) 0.9 (0.8, 1.1) 0.8 (0.7, 1.1) 1.1 (1.0, 1.2)
Lower abdominal pain 1.1 (0.9, 1.4) 0.9 (0.8, 1.1) 1.0 (0.9, 1.2) 1.0 (0.9, 1.1)
Absence of vaginal discharge 3.1 (1.0, 9.3) 0.3 (0.1, 0.9) - -
Absence of vaginal irritation 2.7 (0.9, 8.5) 0.2 (0.1, 0.9) - -
Back pain 1.6 (1.2, 2.1) 0.8 (0.7, 0.9) 0.9 (0.7, 1.1) 1.1 (0.9, 1.3)
Vaginal discharge on 1.1 (1.0, 1.2) 0.7 (0.5, 0.9) 0.6 (0.5, 0.8) 1.1 (1.0, 1.2)
physicalexam
Combination of symptoms
1. dysuria and 22.6
frequency present,
vaginal discharge
and irritation absent
2. dysuria absent, 0.1-0.2
vaginal discharge
or irritation present
3. dysuria or frequency 0.3-0.5
present, vaginal
discharge or
irritation present
*Adapted from Bent 2002
†Adapted from Giesen 2010 (diagnostic value at a reference standard threshold of ≥ 102
CFU/ml)
2. What is the best approach in the management of a patient

suspected to have AUC?
Empiric antibiotic treatment is the most cost-effective
approach in the management of AUC.
Pre-treatment urine culture and sensitivity is NOT
recommended.
Standard urine microscopy and dipstick leukocyte esterase
(LE) and nitrite tests are not prerequisites for treatment.

Summary of Evidence
In a andomi ed cont olled t ial CT omen a ed ea s
old presenting to primary care with suspected uncomplicated UTI
e e andomi ed into fi e mana ement app oaches a empi ic
anti iotics i en immediatel empi ic anti iotics sta ted i
s mptoms pe sist a te ho s c anti iotics o e ed onl i t o o
mo e o the ollo in si ns and s mptoms a e p esent clo d ine
smell ine noct ia and d s ia d anti iotics i en i dipstic is
positi e o eithe nit ite o le coc tes and t ace o lood and e
s mptomatic t eatment initiall then anti iotics ta eted to the specific
pathogen when culture results come out. The study concluded that
all st ate ies es lted in simila s mptom cont ol ith no si nificant
di e ences in se e it o s mptoms o e e s mptoms lasted
lon e in patients ho had to ait at least ho s e o e sta tin
anti iotics and lon e in those ho aited o the c lt e es lts
compared to the immediate antibiotics group.
ince the CT on the fi e mana ement app oaches sho ed no

si nificant di e ence in s mptom cont ol a cost e ecti eness anal sis
as done hich ielded no di e ence in eso ce implications amon
the fi e mana ement app oaches It is ecommended that a cost
e ecti eness anal sis on the mana ement o UC also e cond cted
in the Philippines.
3. Which antibiotics are effective for acute uncomplicated cystitis?

Antibiotics recommended for use in AUC are presented in
Table 4. Efficacy in terms of clinical cure, cost effectiveness,
safety and tolerability were considered in the choice of
antibiotics. In addition, the propensity to cause collateral
damage and local susceptibility rates were given greater
weights in the choice of antibiotic recommendations.
Comment: Collateral damage is the “ecological adverse effects” of

antibiotic therapy. Such adverse effects include selection of drug-
resistant organisms and colonization or infection with multi-drug
resistant organisms.12,13

Comment: Collateral damage is the “ecological adverse effects” of antibiotic therapy. Such adverse
effects include selection of drug-resistant organisms and colonization or infection with multi-drug
resistant organisms.12,13
Table
Table 4. Antibiotics
4. Antibiotics that can be usedthat
for acutecan be used
uncomplicated for acute uncomplicated cystitis
cystitis
Leading Generic
Recommended dose Brand Total Brand Total
Antibiotics
and duration Unit Price (Php) Unit Price (Php)
(Php) (Php)
Primary Nitrofurantoin 100 mg BID for 5 days per N/A N/A N/A N/A
monohydrate/ orem (PO)
macrocrystal (NOT
sold locally)
Nitrofurantoin 100 mg QID for 5 days PO 53.50/cap 1,070.00 N/A N/A
macrocrystals
Fosfomycin 3 g single dose PO 477.00/ 477.00 N/A N/A
trometamol sachet
Alternative Pivmecillinam (NOT 400 mg BID for 3–7 days PO N/A N/A N/A N/A
sold locally)
Ofloxacin 200mg BID for 3 days PO 53.50/tab 321.00 28.00/tab 168.00
Ciprofloxacin 250mg BID for 3 days PO 32.50/tab 195.00 16.25/tab 97.50
Ciprofloxacin 500mg OD for 3 days PO 49.60/tab 148.80 N/A N/A
extended release
Levofloxacin 250mg OD for 3 days PO 189.50/ 284.25 49.00/ 73.50
500 mg tab 500 mg tab
Norfloxacin 400mg BID for 3 days PO 77.50/tab 465.00 32.50/tab 195.00
Amoxicillin- 625mg BID for 7 days PO 48.90/tab 684.60 29.75/tab 416.50
clavulanate
Cefuroxime 250mg BID for 7 days PO 66.50/tab 931.00 36.75/tab 514.50
Cefaclor 500mg TID for 7 days PO 86.00/cap 1,806.00 49.75/cap 1,044.75
Cefixime 200mg BID for 7 days PO 137.50/cap 1,925.00 108.00/tab 1,512.00
Cefpodoxime proxetil 100mg BID for 7 days PO 54.25/tab 759.50 N/A N/A
Ceftibuten 200 mg BID for 7 days PO 136.00/tab 1,904.00 N/A N/A
ONLY if with Trimethoprim- 160/800 mg BID for 3 days PO 33.75/tab 202.50 17.50/ 105.00
proven sulfamethoxazole Tab
susceptibility (TMP-SMX)
*Prices listed were taken from the drug prices of Mercury Drug Store as of December 2013
Ampicillin or amoxicillin should NOT be used for

empirical treatment given the relatively poor efficacy
and the very high prevalence
Guidelines of antimicrobial
on Diagnosis and Management Part 1 9
resistance
of UTI in Adults 2013 Update
to these agents worldwide.
Summary of Evidence
ince the hilippine actice idelines o p in In ectio s
iseases I Tas o ce on UTI has not ecommended the
use of ampicillin and amoxicillin because of the consistently high
resistance rates of E. coli to the said antibiotics see Ta le

In the past data on local esistance ates o E. coli was based
onl on la o ato s eillance s ch as the epa tment o ealth s
ntimic o ial esistance eillance o am ecentl a
p ospecti e st d on the p e alence o t imethop im s l ametho a ole
resistant E.coli among women with uncomplicated UTI was done in
a tertiary hospital in Pasig City. The much lower resistance rates in
this study may be due to rigorous inclusion criteria of the study (only
p e io sl health mostl p emenopa sal omen ith ncomplicated
ac te c stitis and p eloneph itis e e incl ded and a e mo e li el
e ecti e o the p e alence o comm nit ac i ed E. coli resistance
than hat is epo ted in la o ato ased s eillance no led e o
the local antimicrobial susceptibility patterns of E. coli is important in
empirical antibiotic selection for uncomplicated UTI.
Table 5. Percent Resistance of Urinary E. coli (outpatient urine specimens)

Antimicrobial Agent ARSP 2010* ARSP2011** ARSP2012*** AUUTI study 2011+
N=247 N=775 N=988 N=181
TMP-SMX 72 65.8 63.9 41.4
Nitrofurantoin 7.6 11.8 9.8 5.1
Ciprofloxacin 57.4 49 50.6 Levo-5.6
Co-amoxiclav 36.2 27 24.5 11.6
Cefuroxime 59.8 38.9 31.2 5.1
Cefazolin – – – 6.6
Ampicillin 85.4 81.5 – 64.1
Note: *Antimicrobial Resistance Surveillance Program (ARSP), 2010 report 17
**Antimicrobial Resistance Surveillance Program(ARSP), 2011 report 18
*** Antimicrobial Resistance Surveillance Program(ARSP), 2012 report 19
+From a study on uncomplicated UTI in a tertiary hospital in Pasig City 16
T imethop im s l ametho a ole m I o th ee

da s sho ld e sed o c lt e p o en s scepti le
opatho ens d e to hi h p e alence o local esistance
and high failure rates.
Summary of Evidence
The ole o T in the t eatment o UC has e ol ed in ecent
ea s eca se o the chan in landscape in antimic o ial tili ation
and conse ent de elopment o esistance In the pdate o
the In ectio s iseases ociet o me ica I idelines o the
t eatment o ac te ncomplicated c stitis and p eloneph itis T
is still conside ed an app op iate a ent o UC as lon as the
local esistance ates o opatho ens to T do not e ceed
In a andomi ed cont olled t ial o omen ith ac te c stitis

clinical c e ates e e si nificantl lo e amon T t eated
omen ho had a T non s scepti le isolate compa ed
with those who had a susceptible isolate. ence in it o esistance
should be considered in choosing an antimicrobial as it correlates
with clinical and bacteriologic failures.
Nitrofurantoin monohydrate/macrocrystals (100 mg

twice daily for five days) is recommended as the first line
treatment for acute uncomplicated cystitis due to its high
efficacy, minimal resistance, minimal adverse effects, low
propensity for collateral damage, and reasonable cost.
However, the nitrofurantoin monohydrate/macrocrystal
formulation is not locally available. Thus, nitrofurantoin
macrocrystal formulation 100 mg is recommended, but it
should be given four times a day for five days.
Summary of Evidence
it o antoin a ina t act a ent almost e cl si el emplo ed
o t eatment o UC has een sed o mo e than fi e decades
o e e its pop la it as hampe ed conce ns a o t e ficac
tole ance and the ecommended se en da dosin e imen
ecent t ials and meta anal ses sho ed that nit o antoin has
compa a le e ficac ith othe anti iotics sed o t eatin UC
ith inc easin anti iotic esistance and de elopment o collate al
dama e nit o antoin has the ad anta e o lo e esistance ates
and less ad e se e ects than the t aditional anti iotics sed o
uncomplicated cystitis. it o antoin emained acti e a ainst
most opatho ens andomi ed cont olled t ial in sho ed that
patients on nit o antoin mac oc stal m I o th ee da s had
si nificantl ette clinical and acte iolo ic o tcomes compa ed to
placebo. ecent andomi ed cont olled t ial sho ed that a fi e da
co se o nit o antoin monoh d ate mac oc stal m I as
as e ecti e as a th ee da co se o T do le st en th ta let
BID in terms of clinical and microbiologic cure. s stematic e ie
of antimicrobial agents used to treat uncomplicated cystitis in women
sho ed that sho t te m and lon te m c e o nit o antoin as
simila to that o T Compa ed to T nit o antoin
had simila ad e se e ent ates ho e e nit o antoin as less
li el to ca se ash compa ed ith T This same s stematic
e ie sho ed that the nit o antoin o p had hi he sho t te m
s mptomatic c e compa ed ith the eta lactams ntimic o ial
resistance rates of E.coli urine isolates causing AUC consistently
sho ed hi h esistance ates a ainst T hile nit o antoin
emained consistentl acti e s E. coli emonst ation o e ficac

with reports of low drug resistance based on international and local
s scepti ilit patte ns minimal ad e se e ects lo is o collate al
dama e and cost e ecti eness ma e nit o antoin an e cellent
primary drug of choice for AUC.
Fosfomycin (3 g in a single dose) is also a recommended

antibiotic for acute uncomplicated cystitis due to its high
efficacy, convenience of a single dose, low propensity
for collateral damage, good activity against multidrug-
resistant uropathogens, and minimal adverse effects.
However, there are no local resistance data to date.
Summary of Evidence
The con enient sin le dose e imen ood in it o acti it a ainst
esistant am ne ati e ods and minimal p opensit o collate al
dama e ma e os om cin a ational choice T o CTs s ppo ted the
use of fosfomycin trometamol for treatment of UTI as its clinical
e ficac is compa a le ith othe fi st line a ents a ainst UC In
addition a s stematic e ie demonst ated that it has acti it a ainst
multidrug resistant pathogens. ecent meta anal sis compa in
fosfomycin with other antibiotics showed no difference in clinical
s ccess mic o iolo ical s ccess and occ ence o ad e se
e ents In act os om cin as s pe io a ainst t imethop im eta
lactams and nit o antoin in te ms o mic o iolo ic s ccess Aside
om compa a le e ficac the con enience o a sin le dose ma es
os om cin a p omisin d o the t eatment o UC o e e local
s scepti ilit data is c entl not a aila le on this d
Pivmecillinam (400 mg BID for three to seven days) can

be used in areas where it is available, as it has reasonable
treatment efficacy. However, it is not currently available
in the country. Local resistance data is also absent.
Summary of Evidence
i mecillinam an e tended spect m penicillin and the o al o m
o mecillinam has easona le t eatment e ficac o UC eca se
o its specificit o the ina t act and minimal p opensit o
collate al dama e do le lind CT done in eden concl ded
that pi mecillinam as ette than place o in the t eatment o UC
nothe CT sho ed that pi mecillinam at m I o th ee da s
as as e ecti e as no o acin m I o th ee da s in te ms
of early symptomatic cure. In some opean co nt ies its lo

esistance ates ha e made pi mecillinam a pop la fi st line choice
o UC o e e it is not a aila le in the hilippines
Quinolones should NOT be used as a first line drug for

acute uncomplicated cystitis despite its efficacy due to
the high propensity for collateral damage.
Summary of Evidence
l o o inolones a e still accepted as hi hl e ficacio s a ents o
ac te c stitis o e e the I idelines o the t eatment
o ac te ncomplicated c stitis and p eloneph itis pdate eco ni ed
the high risk for collateral damage associated with the use of
o o inolones The specific ad e se e ects o o o inolones
a e in ections ith methicillin esistant S. aureus and increasing
o o inolone esistance o am ne ati e acilli the
considerations in the Philippine setting include endemic infections
s ch as t e c losis and t phoid e e s s ch o o inolones
sho ld e conside ed as alte nati e a ents onl and thei se sho ld
be limited to cases wherein other agents cannot be used.
Beta-lactam agents, including amoxicillin-clavulanate,

cefaclor, cefdinir, cefpodoxime proxetil, ceftibuten, and
cefuroxime are appropriate choices for therapy when
other recommended agents cannot be used.
Summary of Evidence
eta lactams ha e ene all een p o en in e io in c e ates
compared to other agents for treatment of acute uncomplicated
c stitis In the pdate o the I idelines on UTI the
e ficac ates o eta lactam a ents e e lo e than that o T
and o o inolones The post lated mechanism o eta
lactam inferiority in the treatment of UTI was related to its lower rate
o e adication o a inal opatho ens
Th ee CTs di ectl compa ed a eta lactam ith t aditional fi st

line a ents The fi st t ial compa ed the e ficac and sa et o
ce podo ime p o etil m t ice dail o th ee da s ith T
m t ice dail o th ee da s There were no
si nificant di e ences in oth clinical and acte iolo ical o tcomes
The second st d compa ed amo icillin cla lanate m
t ice dail o th ee da s ith cip o o acin m t ice dail o
three days in the treatment of uncomplicated cystitis. Clinical and

mic o iolo ical c e ates o amo icillin cla lanate e e in e io to
that o cip o o acin thi d t ial compa ed ce podo ime p o etil
m t ice dail o th ee da s ith cip o o acin m t ice dail o
three days in the treatment of acute uncomplicated cystitis. Clinical
c e ates o ce podo ime did not each the c ite ia o non in e io it
to cip o o acin
eta lactams a e also associated ith collate al dama e specificall

eme ence o am ne ati e e tended spect m eta lactamase
esistance to these a ents s s ch the a e conside ed as
alte nati e a ents to e sed hen T o o inolones o
nitrofurantoin are contraindicated.
4. What is the effective duration of treatment for acute

uncomplicated cystitis?
Nitrofurantoin should be given for five days, while
fosfomycin is given as a single dose.
For the alternative agents:
• A three day course for fluoroquinolone is recommended.
• A seven-day regimen for beta-lactams (amoxicillin-
clavulanate, cefaclor, cefdinir, cefixime, cefpodoxime
proxetil, ceftibuten, and cefuroxime) is recommended.
Summary of Evidence
One of the reasons why nitrofurantoin was less popular in the past is
the ecommended se en da dosin e imen Initial CTs compa in
nit o antoin ith place o sed a se en da e imen o e e
a andomi ed cont olled t ial done in sho ed that a fi e da
t eatment e imen ith nit o antoin had simila clinical e ficac
compa ed to a th ee da e imen ith T The Tas o ce
the e o e ecommends fi e da d ation o nit o antoin o UC
s stematic e ie compa in os om cin ith se e al anti iotics

sed sin le dose os om cin and sho ed eithe no si nificant
difference between comparators and fosfomycin or some results
a o in the se o os om cin e the e o e ecommend a sin le
dose o sachet o os om cin o UC
hi h alit meta anal sis o t ials ith patients compa ed

a th ee da e imen ith a m lti da fi e da s o lon e e imen o
t eatment o ncomplicated UTI in omen o si nificant di e ence
as noted et een a th ee da e imen and a m lti da e imen
in oth sho t te m and lon te m s mptomatic ail e ates o
all antimic o ial a ents st died The a ents incl ded in the meta

anal sis e e T o o inolones nit o antoin and eta
lactams In te ms o oth sho t te m and lon te m acte iolo ical
ail e a statisticall si nificant di e ence a o in a m lti da
da s e imen as noted o e e in te ms o incidence o ad e se
e ents a statisticall si nificant di e ence a o in the th ee da
e imen as seen s s ch a th ee da o o inolone e imen as
as e ecti e as a da e imen in achie in s mptomatic c e
o e e in cases he e acte iolo ical e adication as indicated
the lon e d ation o t eatment da s as mo e e ecti e
The pdate o the I idelines o the t eatment o ac te

ncomplicated c stitis and p eloneph itis also ad ocated a th ee da
e imen o o o inolones not onl d e to its e ficac t also d e
to the si nificantl hi he ad e se e ent ate o o o inolones This
was further compounded by the issues on collateral damage seen
ith the se o o o inolones ma in the th ee da e imen mo e
appropriate.
o eta lactams the e as no si nificant di e ence et een the

t o t eatment e imens in the incidence o oth sho t te m and lon
term bacteriologic failure. ltho h a th ee da e imen appea ed
to e as e ficacio s as a m lti da e imen e en o eta lactams
the e ficac ates o this antimic o ial class ha e een conside ed
in e io to T o o inolones and nit o antoin This as
d e to the lo e ine concent ation o eta lactams and its in e io
ability in eradicating E. coli in a inal and ecal ese oi s Th s a
se en da e imen is still a anted o eta lactams
5. In elderly women (>65 years) with acute uncomplicated

cystitis, what is the effective duration of treatment?
In otherwise healthy elderly women with AUC, the
recommended duration of treatment is the same as with
the general population (See Table 4).
Summary of Evidence
n pdated Coch ane s stematic e ie that incl ded CTs
patients assessed the e ecti eness o sin le dose sho t
co se and lon co se antimic o ial e imens in the t eatment o
s mptomatic lo e UTI in elde l omen The o tcomes e al ated
incl ded pe sistent UTI clinical ail e ad e se eactions and
t eatment accepta ilit The e as a statisticall si nificant di e ence
in the incidence of persistent UTI in the single dose treatment arm
compa ed to oth the sho t co se and lon co se t eatments
Compa in sho t co se da s ith lon co se da s

t eatment the e as no si nificant di e ence in the incidence o
pe sistent UTI clinical ail e and ad e se eactions The e ie
s ested that the sin le dose the ap as less e ecti e hile the
sho te d ation o the ap as s ficient t eatment o elde l omen
ith ncomplicated s mptomatic lo e UTI
6. What should be done for women whose symptoms worsen,

do not completely resolve, or do not improve after completion
of treatment?
Patients whose symptoms worsen or do not improve
after completion of treatment should have a urine
culture done, and, the antibiotic should be empirically
changed pending result of sensitivity testing.
Patients whose symptoms fail to resolve after treatment
should be managed as complicated UTI.
Summary of Evidence
The tas o ce o nd no ne e idence to s ppo t a chan e in the
ecommendations om the p e io s ideline
atients hose s mptoms o sen o do not imp o e a te the ap

ma ha o a esistant patho en This ill e i e a ine c lt e
and administ ation o a ne anti iotic pendin es lt o the sensiti it
testing.
7. What is the clinical utility of a post-treatment urine culture?

Routine post-treatment urine culture and urinalysis in
patients whose symptoms have completely resolved
are NOT recommended as it does not provide any added
clinical benefit.
Summary of Evidence
The tas o ce o nd no ne e idence to s ppo t a chan e in the
ecommendations om the p e io s ideline
In o mal cost enefit anal sis o data om et ospecti e o se ational

studies showed that routine screening after treatment was costly
pe case detected and p o ided no added clinical enefit A
et ospecti e st d on omen t eated o ac te c stitis as
done to dete mine hethe o tainin a sin le ollo p ine c lt e
ed ced the incidence o s se ent episodes o UTI i t one
omen did not ha e a ollo p c lt e hile had post t eatment

ine c lt es The t o o ps e e e al ith e a ds to ace
eco din o ne ati e int a eno s p elo am UTI p eloneph itis
as mptomatic acte i ia o ec ent UTI episodes mptomatic
UTI de eloped ithin th ee months in o the no ollo p c lt e
o p and o the ollo p c lt e o p mon the omen in
the ollo p c lt e o p onl th ee o t o had a positi e c lt e
and onl one o these th ee de eloped s mptomatic UTI
Algorithm 2. Management of Acute Uncomplicated Cystitis
Healthy non-pregnant woman

with dysuria, frequency, urgency
or hematuria
1
Treat empirically with
recommended oral
antibiotics (Table 4)
2
Reassess at end of
therapy.
3
4
Symptoms YES
resolved? No further treatment.
NO
5
Do urinalysis, urine
culture and change
antibiotics empirically
pending urine C/S results.

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7.

ACUTE UNCOMPLICATED PYELONEPHRITIS IN WOMEN
Section Summary
efinition o ac te ncomplicated p eloneph itis U
AUP is suspected in otherwise healthy women with no clinical
o histo ical e idence o anatomic o nctional olo ic
a no malities ho p esent ith the classic s nd ome o e e
T C chills an pain costo e te al an le tende ness
na sea and omitin ith o itho t si ns and s mptoms o
lower UTI.
a o ato findin s incl de p ia C o cent i ed
ine on inal sis and acte i ia ith co nts o C U
m on ine c lt e
Strong recommendation, Moderate quality of evidence
e t eatment dia nostic tests

Urinalysis and Gram stain are recommended. Urine culture and
sensiti it test sho ld also e pe o med o tinel to acilitate
cost e ecti e se o antimic o ial a ents and eca se o the
potential o se io s se elae i an inapp op iate antimic o ial
agent is used.
t on ecommendation ode ate alit o e idence
Blood cultures are NOT routinely recommended except in
patients with signs of sepsis.
Biomarkers
ioma e s p ocalcitonin mid e ional p o at ial nat i etic
peptide C eacti e p otein a e T ecommended since the
are not clinically useful in determining the need for admission
o in p edictin ad e se o tcomes s ch as ec ence and
p olon ed hospitali ation
Indications for admission

The ollo in a e the indications o admission
Ina ilit to maintain o al h d ation o ta e medications
Conce n a o t compliance
esence o possi le complicatin conditions
e e e illness ith hi h e e se e e pain ma ed de ilit
and signs of sepsis
e e al e imens o nd to e e ecti e in U a e listed in Ta le

ima d s o choice and alte nati e d s a e p esented
ficac cost e ecti eness sa et tole a ilit local s scepti ilit
and propensity for collateral damage were considered for the
choice of the antibiotic.
The aminopenicillins ampicillin o amo icillin and fi st ene ation

cephalosporins are NOT recommended because of the high
p e alence o esistance and inc eased ec ence ates in
patients i en these eta lactams
eca se o hi h esistance ates to T this d is T

recommended for empiric treatment but can be used when
the organism is found to be susceptible on urine culture and
sensiti it
inolones a e ecommended as the fi st line t eatment o ac te

ncomplicated p eloneph itis not e i in hospital admission
In patients not e i in hospital admission an initial sin le I

IM dose of ceftriaxone or aminoglycoside may be considered
ollo ed an o the o al anti iotics in Ta le
o patients ith ac te ncomplicated p eloneph itis e i in

hospitali ation ce t ia one o o inolones o amino l cosides
a e ecommended as empi ic fi st line t eatment
Int a eno s anti iotics can e shi ted to an o the listed o al

antibiotics once the patient is afebrile and can tolerate oral drugs.
The choice of continued antibiotic therapy should be guided by
the ine c lt e and sensiti it es lts once a aila le
o s spected ente ococcal in ection ampicillin ma e com ined

with an aminoglycoside.
Weak recommendation, Low quality of evidence
Ca apenems and pipe acillin ta o actam sho ld e ese ed

o ac te p eloneph itis ca sed m lti d esistant o anisms
that are susceptible to either drug.

The recommended duration of t eatment is da s elected
o o inolonescan e i en o da s
ole o adiolo ic ima in

o tine olo ic e al ation and o tine se o ima in
procedures are NOT recommended.
Conside ea l adiolo ic e al ation i the patient has a histo o

olithiasis ine p o enal ins ficienc
Conside adiolo ic e al ation i the patient emains e ile

ithin ho s o t eatment o i s mptoms ec to le o t the
p esence o neph olithiasis ina t act o st ction enal o
pe ineph ic a scesses o othe complications o p eloneph itis
Obtain urologic consultation if workup shows abnormalities.

ollo p la o ato tests

In patients who are clinically responding to therapy (usually
appa ent in ho s a te initiation o t eatment a ollo p
urine culture is NOT necessary.
o tine post t eatment c lt es in patients ho a e clinicall

imp o ed a e also not ecommended
In omen hose s mptoms do not imp o e d in the ap and

in those hose s mptoms ec a te t eatment a epeat ine
c lt e and sensiti it test sho ld e pe o med
ec ence o s mptoms
ec ence o s mptoms e i es anti iotic t eatment ased on
ine c lt e and sensiti it test es lts in addition to assessin
for underlying genitourologic abnormality.
The d ation o e t eatment in the a sence o a olo ic

abnormality is two weeks.

o patients hose s mptoms ec and hose c lt e sho s
the same o anism as the initial in ectin o anism a o to
si ee e imen is ecommended

1. When is AUP suspected?
AUP is suspected in otherwise healthy women with
no clinical or historical evidence of anatomic or
functional urologic abnormalities, who present with the
classic syndrome of fever (T≥38°C), chills, flank pain,
costovertebral angle tenderness, nausea and vomiting,
with or without signs and symptoms of lower UTI.1
Laboratory findings include pyuria (≥5 WBC/HPF of
centrifuged urine) on urinalysis and bacteriuria with
counts of ≥10,000 CFU/mL on urine culture.2
Summary of Evidence
Acute pyelonephritis usually occurs in otherwise healthy women;
ho e e in o mation e a din is acto s o p eloneph itis is
limited In a pop lation ased case cont ol st d o omen ith
p eloneph itis to ea s o a e the acto s associated ith
p eloneph itis is ee e enc o se al inte co se in the
p e io s da s odds atio CI o times
pe ee ecent UTI CI dia etes
CI ecent incontinence CI
ne se al pa tne in the p e io s ea CI
ecent spe micide se CI and UTI
histo in the pa ticipant s mothe CI
2. What are the recommended diagnostic tests for acute

uncomplicated pyelonephritis?
Urinalysis and Gram stain are recommended. Urine
culture and sensitivity test should also be performed
routinely to facilitate cost-effective use of antimicrobial
agents and because of the potential for serious sequelae
if an inappropriate antimicrobial agent is used.
Blood cultures are NOT routinely recommended except

in patients with signs of sepsis.

ote i ns o sepsis as desc i ed in the p e io s ideline incl de
the p esence o an t o o the ollo in
Tempe at e o
Co o
C
e openia C o le oc tosis C
Tach ca dia eats min
Tachp nea min o aC mm
potension mm o mm d op om
baseline)
Summary of Evidence
In a et ospecti e st d in o ea a p ospecti e data ase o
omen ith p eloneph itis as anal sed to const ct and alidate
a model that aimed to p edict acte emia and di ect the p ope
se o lood c lt es The ollo in e e identified as independent
is acto s o acte emia a e ea s omitin
hea t ate eats min se mented ne t ophils
and ine C ei hts e e
assi ned to each acto total sco e o and the model st atified
patients into ha in lo to inte mediate to o hi h
to is o acte emia In concl sion the said model as help l
in assessing the need for blood cultures and the need for hospital
admission o int a eno s anti iotic administ ation in patients ith
uncomplicated pyelonephritis.
Blood cultures contribute to the management of acute pyelonephritis

when the blood culture results are discordant with the results of the
ine c lt e p ospecti e o se ational m lticente coho t st d
determined the risk factors for bacteremia with a uropathogen that
as not c lt ed o eco ni ed in the ine e al a le patients
e e ine c lt e positi e and e e positi e
o acte emia i e pe cent o the lood c lt es e e disco dant
ith the ine c lt e The p esence o a ina cathete
CI mali nanc CI and acti e
antimic o ial UTI t eatment CI e e statisticall
si nificant acto s associated ith disco dant es lts The mo talit
ates a te a da ollo p e e as ollo s o e all ate
patients ith disco dant es lts s patients ith conco dant
es lts is atio CI o e e the
p esence o ina cathete and acti e antimic o ial UTI t eatment
are characteristics of complicated UTI.
In a p ospecti e st d elasco et al 7 he e the anal ed the

data o omen olde than ea s old onl o the
omen had disco dant c lt e es lts odification o initial anti iotic
therapy based on culture results was not needed. There was also

no di e ence in the clinical e ol tion o the in ection in oth the
discordant and the nondiscordant groups. The study concluded that
blood cultures may not be routinely needed.7
3. Can biomarkers help determine which patients can be treated

as outpatients, or which patients will have adverse outcomes?
Biomarkers (procalcitonin, mid-regional pro-atrial
natriuretic peptide, C-reactive protein) are NOT
recommended since they are not clinically useful in
determining the need for admission or in predicting
adverse outcomes such as recurrence and prolonged
hospitalization.
Summary of Evidence
m lticente p ospecti e o se ational st d in eme enc
depa tments in ance e al ated consec ti e patients to
assess the e ecti eness o p ocalcitonin CT mid e ional p o
at ial nat i etic peptide and C eacti e p otein C
measurements in guiding emergency physicians on deciding if a
patient with acute pyelonephritis should be admitted to the hospital.
e o mance cha acte istics e e tested o a io s c t o s o C
CT and The li elihood atios e e not clinicall ele ant
hate e the ioma e o th eshold The st d concl ded that none
o these th ee ma e s co ld elia l help ph sicians in thei decision
making process.
nothe ench st d e al ated the disc iminato po e and

p edicti e acc ac o p ocalcitonin o ad e se o tcomes in patients
ith ac te p eloneph itis ineteen pe cent o patients anal ed
had ad e se medical o tcomes hich incl ded a pe cei ed
need o hospitali ation p esence o se e e sepsis defined the
p esence o concomitant s stemic in ammato esponse and
o an d s nction ent olo ic s ical p oced es elated to
p eloneph itis e idence o enal a scess admission to intensi e
ca e s se ent hospitali ation and p eloneph itis elated
death ocalcitonin a ied idel and altho h the median le el
as hi he in patients ith ad e se medical o tcomes compa ed
ith those itho t ad e se medical o tcomes the di e ence as not
statisticall si nificant n m s n m p The e
was no useful threshold that could accurately discriminate between
the two groups.
The tilit o p ocalcitonin in p edictin acte emia as e al ated in

a p ospecti e o se ational m lticente coho t st d o ad lts

ith e ile UTI sin le p ocalcitonin le el had the est
dia nostic pe o mance in p edictin the p esence o acte emia
sensiti it CI specificit CI
The use of this biomarker decreased the number of blood cultures
ta en t still ena led identification o to o patients
ith acte emia This t anslated to cost sa in s o the patients
o e e lood c lt es a e ecommended to e ta en p io to the
initiation o anti iotics aitin o the es lts o p ocalcitonin le els to
dete mine hich patients o ld e i e lood c lt es o ld es lt in
inappropriate delay in treatment.
The se o C eacti e p otein as a ma e o p olon ed hospitali ation

and U ec ence as anal ed in consec ti e patients in si
di e ent instit tes in o th o ea imple lo istic e ession anal sis
e ealed that the e as a si nificant co elation et een the C le el
at discha e and ec ence o ac te p eloneph itis p The e
as eate incidence o ec ence in patients ith C m d
at discha e compa ed ith patients ith C m d p
atients ith a ma imal C o m d d in admission on the
othe hand had lon e hospitali ation sta s compa ed to patients
ith ma imal C m d p The need o int a eno s
anti iotic the ap in these patients as eate p The
clinical tilit o no in that patients ith ce tain C le els ha e
a hi he ec ence ate o ha e p olon ed hospitali ation emains
unclear.
eca se o the limited a aila ilit limited clinical tilit and the cost
o these ioma e s especiall in eso ce limited settin s o tine
use of biomarkers in the management of AUP is not recommended.
4. What are the indications for admission in patients with acute

The following are the indications for admission:
• Inability to maintain oral hydration or take medications;
• Concern about compliance;
• Presence of possible complicating conditions;
• Severe illness with high fever, severe pain, marked
debility, and signs of sepsis
Summary of Evidence
The e a e no ne CTs di ectl compa in inpatient s o tpatient
mana ement o e e in the m lticente do le lind andomi ed
non in e io it st d la sne et al compa in a fi e da co se o
le o o acin m ith a da co se o cip o o acin m

Presence of possible complicating conditions;
Severe illness with high fever, severe pain, marked debility, and signs of sepsis
I most
Summary o the s ects e e t eated ith o al anti iotics Patients
of Evidence
ithareac
There no newte RCTs
p eloneph itis inpatient
directly comparing incl vs.dinoutpatient
ones ith However,
management. acte emia ee
in the multicenter,
treated in
double-blind, the community
randomized and
non-inferiority study demonstrated
by Klausner et al. comparinghigh microbiologic
a five-day and
course of levofloxacin 750
clinical
mg OD withsa ccess ates
10-day course ith oth
of ciprofloxacin 500lemgoBID,o most
acinof and cip owere
the subjects o treated
acin with Thisoral
showed
antibiotics. 12 that patients with AUP can be safely treated as outpatients
Patients with acute pyelonephritis, including ones with bacteremia, were treated in the community
ith anti
and demonstrated iotics that ha e
high microbiologic ood o
and clinical al rates
success ioa withaila
bothilit
levofloxacin and ciprofloxacin. This
showed that patients with AUP can be safely treated as outpatients with antibiotics that have good oral
5. What drugs can be used for empiric treatment of acute
bioavailability.
5. What drugs Several
can be usedregimens found of
for empiric treatment toacute
be uncomplicated
effective inpyelonephritis?
AUP are listed in
Table 6. Primary drugs of choice and alternative drugs are
Several regimens found to be effective in AUP are listed in Table 6. Primary drugs of choice
presented. Efficacy, cost effectiveness, safety, tolerability,
and alternative drugs are presented.
local susceptibility, andEfficacy, cost effectiveness,
propensity safety, tolerability,
for collateral damage local
susceptibility, and propensity for
were considered forcollateral
the choicedamage of werethe
considered for the choice of the
antibiotic.
antibiotic.
Table6. 6.
Table Empiric
Empiric treatment
treatment regimensregimens for acute uncomplicated
for acute uncomplicated pyelonephritis pyelonephritis
Antibiotic Dose, Frequency and Duration
ORAL
Primary Ciprofloxacin 500 mg BID for 7-10 days
Ciprofloxacin extended release 1000 mg OD for 7 days
Levofloxacin 250 mg OD for 7-10 days
750 mg OD for 5 days
Ofloxacin 400 mg BID for 14 days
Alternative Cefixime 400 mg OD for 14 days
Ceftibuten 400 mg OD for 14 days
Cefuroxime 500 mg BID for 14 days
Co-amoxiclav (when GS shows gram-positive orgs) 625 mg TID for 14 days
PARENTERAL (given until patient is afebrile)
Primary Ceftriaxone 1-2 g q24 hours
Ciprofloxacin 400 mg q12 hours
Levofloxacin 250-750 mg q24 hours
Ofloxacin 200-400 mg q 12 hours
Amikacin 15 mg/kg BW q 24 hours
Gentamicin +/- ampicillin 3-5 mg/kg BW q24 hours
Alternative Ampicillin-sulbactam (when GS shows gram- 1.5 g q6 hours
positive orgs Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1 23
Reserved for Ertapenem (if ESBL prevalence > 10%) 1 g q24 hours
MDROs Piperacillin-tazobactam 2.25-4.5 g q6-8 hours
The aminopenicillins (ampicillin or amoxicillin) and first generation cephalosporins are NOT
recommended because of the high prevalence of resistance and increased recurrence rates in
patients given these
Guidelines beta-lactams.
on Diagnosis and Management of UTI in Adults 2013 Update Part 1
The aminopenicillins (ampicillin or amoxicillin) and
first generation cephalosporins are NOT recommended
because of the high prevalence of resistance and increased
recurrence rates in patients given these beta-lactams.
Because of high resistance rates to TMP-SMX, this drug

is NOT recommended for empiric treatment but it can be
used when the organism is found to be susceptible on urine
culture and sensitivity.
Quinolones are recommended as the first line treatment for acute

uncomplicated pyelonephritis not requiring hospital admission.
In patients not requiring hospital admission, an initial

single IV/IM dose of ceftriaxone or aminoglycoside may be
considered followed by any of the oral antibiotics in Table 6.
For patients with acute uncomplicated pyelonephritis requiring

hospitalization, ceftriaxone, fluoroquinolones, or aminoglycosides
are recommended as empiric first-line treatment.
Intravenous antibiotics can be shifted to any of the listed oral

antibiotics once the patient is afebrile and can tolerate oral drugs.
The choice of continued antibiotic therapy should be guided by
the urine culture and sensitivity results once available.
For suspected enterococcal infection, ampicillin may be

combined with an aminoglycoside.
Carbapenems and piperacillin-tazobactam should be

reserved for acute pyelonephritis caused by multi-drug
resistant organisms that are susceptible to either drug.
Summary of Evidence
The e e e no andomi ed clinical t ials on t eatment o U solel
All of the studies included males and complicated UTI.

Ciprofloxacin and extended-release Ciprofloxacin
ne andomi ed do le lind t ial compa ed the e ficac o
m o e tended elease cip o o acin Cip o once dail
ith cip o o acin m t ice dail each i en o da s in
patients with complicated UTI or acute pyelonephritis. The clinical
and acte iolo ic c e ates did not di e si nificantl The ates o
ad e se e ents e e simila
Levofloxacin vs. ciprofloxacin

m lticente do le lind andomi ed non in e io it t ial compa ed
le o o acin m I dail o fi e da s ith cip o o acin
m I and o m I o da s in patients ith U and
complicated UTI. o p anal sis o the patients ith U
sho ed that mic o iolo ical e adication as achie ed in o the
le o o acin t eated patients and o cip o o acin t eated
patients in the modified intention to t eat ITT pop lation
In the mic o iolo icall e al a le pop lation o
the le o o acin t eated s ects s o the cip o o acin
t eated s ects achie ed mic o iolo ic e adication Clinical s ccess
as achie ed in o le o o acin t eated s ects in the ITT
pop lation s in the cip o o acin t eated s ects In the
pop lation clinical s ccess as achie ed in o the le o o acin
t eated s cip o o acin t eated s ects
Ertapenem vs. ceftriaxone

com ined anal sis o t o andomi ed do le lind m lticente
trials compa in e tapenem once a da ith ce t ia one once
a da ollo ed app op iate o al the ap a te da s o pa ente al
the ap sho ed that o e tapenem t eated and o
ce t ia one t eated mic o iolo icall e al a le ac te p eloneph itis
patients achie ed mic o iolo ical esponse at completion o pa ente al
the ap t test o c e o e tapenem t eated patients s
o ce t ia one t eated patients had mic o iolo ic esponse
d e se e ents e e also simila in oth st d o ps
TMP-SMX resistance
E. coli is the most p e alent patho en o ncomplicated UTI
Inc easin T esistance ma es this anti iotic a poo choice
o U In a ecent s eillance st d done in ni e sit a filiated
eme enc depa tments in the United tates o me ica om
T esistance as o nd to e app o imatel
Fluoroquinolone resistance
In the same st d in ni e sit a filiated eme enc depa tments
in the United tates mentioned ea lie o o inolone esistance

as The I ideline ecommended an initial one time
int a eno s dose o a lon actin pa ente al antimic o ial s ch as
o ce t ia one o a consolidated h dose o an amino l coside
i the p e alence o o o inolone esistance e ceeds This
ecommendation e i ed an acc ate no led e o the p e alence
o esistance in the st died pop lation The ntimic o ial esistance
eillance o am ata hich consolidated the pe cent
resistance of urinary E. coli from different regional hospitals in the
hilippines epo ted cip o o acin esistance o o e e
this ma not e ep esentati e o the t e p e alence o esistance
in the community since the E. coli isolates were submitted from
o e nment hospitals and not limited to patients ith ncomplicated
UTI p ospecti e coho t on ac te ncomplicated UTI incl din ac te
p eloneph itis om a p i ate te tia hospital in asi Cit epo ted
o o inolone esistance p e alence o less than
i en the lac o elia le epidemiolo ic data on the p e alence o

o o inolone esistance amon opatho ens no led e o is
acto s o o o inolone esistance ma aid in the selection o initial
antibiotics for acute pyelonephritis. A nested case–control study within
a cohort study of adults with febrile UTI seen in primary healthcare
centers or emergency departments in the Netherlands found that
ecent hospitali ation ina cathete and o o inolone se in
the past si months e e independent is acto s o o o inolone
esistance in comm nit onset e ile UTI ca sed E. coli.
Extended spectrum beta lactamase producing E. coli

In a et ospecti e coho t st d in o ea e tended spect m eta
lactamase production in E. coli isolates as in comm nit
associated ac te p eloneph itis s in healthca e associated
ac te p eloneph itis p In a p ospecti e coho t o
patients ith UC and U om a te tia hospital in asi Cit E.
coli as the most common opatho en isolated comp isin o
isolates ith ate o p od ction o t o E. coli isolates
causing uncomplicated UTI.
ltiple st dies ha e so ht to dete mine the p e alence ate o

comm nit ac i ed UTIs ca sed p od cin o anisms
et ospecti e st d in it e land o nd that amon patients ith
UTI d e to p od cin E. coli had comm nit ac i ed
UTI and had healthca e associated UTI esistance ates
o commonl sed anti iotics in comm nit ac i ed isolates e e as
ollo s amo icillin cla lanic acid esistance cip o o acin
esistance no o acin esistance t imethop im
s l ametho a ole esistance nit o antoin esistance

and os om cin esistance It should be noted that these isolates
ha e hi h esistance to commonl sed antimic o ials e cept o
nitrofurantoin and fosfomycin.
In a et ospecti e st d o patients ith acte emic UTIs m ltiple

lo istic e ession anal sis sho ed that male ende
CI and healthca e acilit esidenc CI
e e independent is acto s o p od cin in ections
mon patients ith UTI in o ea e e in ected ith
p od cin acte ia and the is o s ch an in ection as t ice
hi he in inpatient UTI The m lti a iate anal sis sho ed that the
ollo in e e clinicall si nificant is acto s o p od cin
opatho ens inpatient o i in CI p e io s
hospitali ation CI emale se CI
ole cathete i ation CI e pos e
to ce aclo CI and e pos e to ce mino
CI
nothe p ospecti e st d sho ed an positi it ate o

in ncomplicated UTIs and in complicated
UTIs p lti a iate anal sis sho ed that the ollo in ee
associated ith positi e E. coli ha in mo e than th ee
ina t act in ection episodes in the p ecedin ea
CI se o a eta lactam anti iotic in the p ecedin th ee
months CI and p ostatic disease
CI n the othe hand anothe case cont ol
st d done in painsho ed that amon di e ent acto s st died
onl p e io s e pos e to second ene ation cephalospo ins as
st on l associated ith p od cin E. coli a te m lti a iate
anal sis CI Patients presenting with acute
p eloneph itis ith is acto s o p od cin o anisms ma
enefit om ea l initiation o the ap e ecti e o these o anisms
6. What is the effective duration of treatment for AUP?

The recommended duration of treatment is 14 days.
Selected fluoroquinolones can be given for 7-10 days.
Summary of Evidence
The standa d ecommended d ation o t eatment o U is da s
o e e in an e a o inc easin anti iotic esistance sho t co ses
of antibiotics are preferred.
The UTI T t ial an ie oop et al is an on oin andomi ed

place o cont olled do le lind m lticente non in e io it t ial on

patients in the ethe lands ith comm nit ac i ed e ile UTI
It compa ed se en da s o cip o o acin o se en da s o empi ical
lactam entamicin I ith ea l s itch to o al cip o o acin
ollo ed se en da s o place o sho t t eatment a m s
se en da s o cip o o acin o se en da s o empi ical lactam
entamicin I ith ea l s itch to o al cip o o acin ollo ed
se en da s o linded cip o o acin hich ep esented the standa d
da t eatment a m
In the st d ete son et al le o o acin m i en o fi e

da s had simila e ficac ates to cip o o acin I m I
i en o da s
ecent p ospecti e non in e io it t ial compa in the e ficac

o cip o o acin o da s s da s in omen ith comm nit
ac i ed U concl ded that ac te p eloneph itis in omen
incl din olde omen and those ith mo e se e e in ection can
e t eated s ccess ll and sa el ith o al cip o o acin o se en
days.
Th s in a sta le patient dia nosed ith U itho t an

cont aindication a se en da d ation o t eatment ith selected
inolones can e sed
7. Who will require work up for urologic abnormalities?

Routine urologic evaluation and routine use of imaging
procedures are NOT recommended.
Consider early radiologic evaluation if the patient has a

history of urolithiasis, urine pH ≥ 7.0 or renal insufficiency.
Consider radiologic evaluation if the patient remains

febrile within 72 hours of treatment or if symptoms recur
to rule out the presence of nephrolithiasis, urinary tract
obstruction, renal or perinephric abscesses, or other
complications of pyelonephritis.
Obtain urologic consultation if workup shows abnormalities.


Summary of Evidence
ecommendations e a din urologic e al ation ha e een ased
mostl on e pe t opinion and small sin le cente o se ational
st dies p ospecti e o se ational st d on ad lt patients ith
febrile UTI in eight emergency departments in the Netherlands sought
to de elop a clinical le to help asce tain the need o adiolo ic
ima in In the m lti a iate anal sis the ollo in p edicto s e e
si nificantl associated ith the findin o a clinicall ele ant olo ic
diso de histo o olithiasis ine p and enal ins ficienc
lome la filt ation ate ased on modification o diet in enal
disease o m la m min m ). The prediction rule
incl ded these th ee a ia les ith one point assi ned o each In the
de i ation coho t n ith a c t o point o point the ne ati e
p edicti e al e o an clinical ele ant adiolo ic findin as
positi e p edicti e al e as sensiti it as
and the specificit as In the alidation coho t n the
as and as o clinicall ele ant adiolo ic findin s
The estimated a elati e ed ction o in adiolo ic ima in i
the p ediction le as sed The median d ation o e e as t o
da s in this st d ation o e e da s as not associated ith
an clinicall ele ant adiolo ic findin ni a iate CI
8. Is a follow-up urine culture recommended?

In patients who are clinically responding to therapy
(usually apparent in <72 hours after initiation of
treatment), a follow-up urine culture is NOT necessary.
Routine post-treatment cultures in patients who are

clinically improved are also not recommended.
In women whose symptoms do not improve during therapy

and in those whose symptoms recur after treatment, a repeat
urine culture and sensitivity test should be performed.

Summary of Evidence
The ecommendations e e ased on e pe t opinion consens s e
did not find an st dies demonst atin the clinical tilit o ollo p
ine c lt es d in t eatment and post t eatment o patients ho
a e espondin to the ap In patients not imp o in it is necessa to
repeat the urine culture and sensiti it to le o t anti iotic esistance
9. What is the recommended management for patients whose

symptoms recur?
Recurrence of symptoms requires antibiotic treatment based
on urine culture and sensitivity test results, in addition to
assessing for underlying genitourologic abnormality.
The duration of re-treatment in the absence of a urologic

For patients whose symptoms recur and whose culture

shows the same organism as the initial infecting
organism, a four- to six-week regimen is recommended.
Summary of Evidence
e did not find an andomi ed cont olled t ials that dete mined the
optimum duration of treatment for women with recurrent pyelonephritis.

Algorithm 3. Treatment of acute uncomplicated pyelonephritis
in non-pregnant women
Healthy non-pregnant woman

with acute uncomplicated
pyelonephritis
1
Assess severity of
illness & likelihood of
adherence to treatment.
2 3
Septic too 1. Admit patient.

ill or likely to YES 2. Do urinalysis, urine GS, C/S.
be non- 3. Do blood C/S 2x if septic.
adherent? 4. Start empiric IV antibiotics
(Table 6).
NO
8
1. Do urinalysis, urine 4
GS, C/S.
Reassess patient
2. Treat as outpatient. within 72 hours. 6
3. Start empiric oral 1. Shift IV antibiotics
antibiotics (Table 6) 5 to oral once patient
based on gram is afebrile & van
stain results. tolerate oral
Symptoms YES medications.
improved on
Day 3? 2. Continue antibiotics
for 10-14 days.
NO 3. Antibiotic choice
7 should be guided
by urine C/S results
1. Repeat urine C/S. once available.
2. Consider foing
radiologic
evaluation.
3. Consider urologic
consultation.

References
in eam T tamm n app oach to e al atin anti acte ial
a ents in the t eatment o ina t act in ection Clin In ect is ppl
disc ssion
o e ts antitati e ine c lt e in patients ith ina t act in ection and
acte emia m Clin athol
choles ooton T o e ts pta tapleton tamm is
acto s ssociated ith c te eloneph itis in ealth omen nn Inte n ed

Infectious Disease. The Philippine Clinical Practice Guidelines on the
ia nosisand ana ement o U ina T act In ections in d lts Update
e on Cit hilippines I hilippine ociet o ic o iolo and
In ectio s iseases
im im o im T ee ee et al simple model to p edict
bacteremia in women with acute pyelonephritis. The Journal of infection [Internet].
lse ie td cited ct aila le om http
nc i nlm nih o p med
an ie oop C onten T o t ec e oene eld ansen
C et al is acto s o acte emia ith opatho en not c lt ed om ine in
ad lts ith e ile ina t act in ection Clinical in ectio s diseases an o ficial
p lication o the In ectio s iseases ociet o me ica Inte net n
cited ct e aila le om http nc i nlm nih o
p med
elasco a t ne o eno a t ne o ca ada i a anco
et al lood c lt es o omen ith ncomplicated ac te p eloneph itis a e the
necessa Clinical in ectio s diseases an o ficial p lication o the In ectio s
iseases ociet o me ica Inte net ct aila le
om http nc i nlm nih o p med
Claessens chmidt ata d a a e o a s ate et al
Can C eacti e p otein p ocalcitonin and mid e ional p o at ial nat i etic
peptide meas ements ide choice o in patient o o t patient ca e in
ac te p eloneph itis ioma e s In epsis I m lticent e st d Clinical
mic o iolo and in ection the o ficial p lication o the opean ociet o
Clinical ic o iolo and In ectio s iseases Inte net n
aila le om http nc i nlm nih o p med
emiale ena d o te ea a o allo m Calmettes et
al sin le p ocalcitonin le el does not p edict ad e se o tcomes o omen
ith p eloneph itis opean olo Inte net a cited ct
an ie oop C onten T an t o t i pe oene eld
ec e et al ocalcitonin e ects acte emia and acte ial load in osepsis
s nd ome a p ospecti e o se ational st d C itical ca e ondon n land
Inte net io ed Cent al td an cited ct aila le
om http p medcent al nih o a ticle ende c i a tid tool
pmcent e ende t pe a st act
an Cho I eon on ee on et al Clinical
implication o se m C eacti e p otein in patients ith ncomplicated ac te
p eloneph itis as ma e o p olon ed hospitali ation and ec ence U olo
Inte net lse ie Inc lse ie Inc an cited ct
la sne a o n ete son a l hasha ishe C et al
t ial o le o o acin m once dail o da s e s s cip o o acin m
and o m t ice dail o da s in the t eatment o ac te p eloneph itis
C ent medical esea ch and opinion Inte net o cited ct

Talan a lim e I icolle on o als Ch ch a nce
dail e tended elease cip o o acin o complicated ina t act in ections and
ac te ncomplicated p eloneph itis The o nal o olo Inte net e
cited ct t aila le om http nc i nlm nih
o p med
ete son a l hasha ishe C ahn do le lind andomi ed
compa ison o le o o acin m once dail o fi e da s ith cip o o acin
m t ice dail o da s o the t eatment o complicated ina t act
in ections and ac te p eloneph itis U olo Inte net an cited ct
imene c aso ich Ca i as ian I Im ea lt oods et
al ospecti e lticente andomi ed o le lind t d Compa in
tapenem and Ce t ia one ollo ed pp op iate al The ap o
Complicated U ina T act In ections in d lts U olo
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et al tapenem e s s Ce t ia one ollo ed pp op iate al The ap
o T eatment o Complicated U ina T act In ections in d lts es lts o a
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multicentre trials comparing ertapenem and ceftriaxone followed by appropriate
o al the ap The o nal o antimic o ial chemothe ap Inte net n cited
ep ppl ii aila le om http nc i nlm nih o
p med
a e lo ens ani a ote ed ich edman Int a eno s
do ipenem at milli ams e s s le o o acin at milli ams ith an option
to s itch to o al the ap o t eatment o complicated lo e ina t act in ection
and p eloneph itis ntimic o ial a ents and chemothe ap Inte net ep
cited ep aila le om http p medcent al
nih o a ticle ende c i a tid tool pmcent e ende t pe a st act
Talan a ishnadasan ahamian tamm o an e alence
and is acto anal sis o t imethop im s l ametho a ole and o o inolone
esistant sche ichia coli in ection amon eme enc depa tment patients
ith p eloneph itis Clinical in ectio s diseases an o ficial p lication o the
In ectio s iseases ociet o me ica Inte net o cited ct
pta ooton T a e llt Col an ille et al Inte national
clinical practice guidelines for the treatment of acute uncomplicated cystitis and
p eloneph itis in omen pdate the In ectio s iseases ociet o
me ica and the opean ociet o ic o iolo and In ectio s iseases Clin
In ect is a e
ntimic o ial esistance eillance e e ence a o ato ntimic o ial
esistance eillance o am nn al epo t pp
an c an co le and ia laa ta amponia enson
et al e alence and is acto s o t imethop im s l ametho a ole esistant
coli in ncomplicated ina t act in ections in a de elopin co nt oste
session p esented at st Inte science Con e ence on ntimic o ial ents and
Chemothe ap IC C Chica o Illinois U
an de ta e an ie oop C altansin an t o t oene eld
ec e et al is acto s o o o inolone esistant sche ichia coli
in ad lts ith comm nit onset e ile ina t act in ection The o nal o
antimic o ial chemothe ap Inte net a cited ct
a an C I oo a an i et al Clinical implications
o healthca e associated in ection in patients ith comm nit onset ac te
p eloneph itis candina ian o nal o in ectio s diseases Inte net

cited ct aila le om http nc i nlm nih o
p med
eie e e inden e C asse tended spect m lactamase
p od cin am ne ati e patho ens in comm nit ac i ed ina t act
in ections an inc easin challen e o antimic o ial the ap In ection Inte net
cited ep aila le om http nc i nlm
nih o p med
an C in C han T Chi C eh et al Impact o
tended spect m lactamase p od cin sche ichia coli and le siella
pne moniae on the o tcome o comm nit onset acte emic ina t act
in ections o nal o mic o iolo imm nolo and in ection ei mian an
an a hi Inte net Tai an ociet o ic o iolo n cited ct
ee ee C ee e alence and is acto s o e tended spect m
eta lactamase p od cin opatho ens in patients ith ina t act in ection
o ean o nal o olo Inte net l cited ct
aila le om http p medcent al nih o a ticle ende c i a tid
tool pmcent e ende t pe a st act
ap slan e e hano l Cola o l do an Tim a na et
al is acto s o e tended spect m eta lactamase positi it in opatho enic
sche ichia coli isolated om comm nit ac i ed ina t act in ections Clinical
mic o iolo and in ection the o ficial p lication o the opean ociet o
Clinical ic o iolo and In ectio s iseases Inte net e
Cal o oman e ca ins me idal C intana et al is
acto s o comm nit onset ina t act in ections d e to sche ichia coli
ha o in e tended spect m eta lactamases The o nal o antimic o ial
chemothe ap Inte net p cited ct aila le
om http nc i nlm nih o p med
an ie oop C an t o t ssendel t l e ie e ten
oste T et al T eatment d ation o e ile ina t act in ection UTI T
t ial a andomi ed place o cont olled m lticente t ial compa in sho t da s
anti iotic t eatment ith con entional t eatment da s t d otocol
C In ect is Inte net aila le om http iomedcent al
com
and e T oo e mansson ahlmete lenstie na
anne d et al Cip o o acin o da s e s s da s in omen ith ac te
p eloneph itis a andomised open la el and do le lind place o cont olled
non in e io it t ial The ancet Inte net aila le om http d doi
o
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et al edictin the need o adiolo ic ima in in ad lts ith e ile
ina t act in ection Clinical in ectio s diseases an o ficial p lication o the
In ectio s iseases ociet o me ica Inte net ec cited ct

urinAry trAct infections in pregnAncy
Asymptomatic Bacteriuria
Acute Cystitis
Acute Uncomplicated Pyelonephritis

URINARY TRACT INFECTIONS IN PREGNANCY
ASYMPTOMATIC BACTERIURIA IN PREGNANCY
Section Summary
efinition o as mptomatic acte i ia
in p e nanc is the p esence o C Um o
the same opatho en in t o consec ti e midst eam ine
specimens o C U m o a sin le opatho en in one
cathete i ed ine specimen mptoms att i ta le to ina
infection should be absent.
In settin s he e o tainin t o consec ti e ine c lt es is

not easi le o is di fic lt one ine c lt e is an accepta le
alte nati e o the dia nosis o in p e nanc
Indication for screening

c een p e nant omen o as mptomatic acte i iaonce
et een the th to th ee a e o estation peea l
on the th week AOG.
Diagnostic test
standa d ine c lt e o clean catch midst eam ine is the
test of choice in screening for asymptomatic bacteriuria.
Urinalysis is not recommended as an initial screening test.

Strong recommendation, high quality of evidence
U ine dipstic s o le oc te este ase and o nit ite tests a e not

recommended for screening for asymptomatic bacteriuria .
In the a sence o ine c lt e ine am stain o ncent i ed

ine mo e than one o anism pe oil imme sion field is
recommended for screening for asymptomatic bacteriuria in
pregnancy.
ipslide c lt e techni e ma e sed as an alte nati e to ine

c lt e in settin s he e it is a aila le

Antibiotic treatment for asymptomatic bacteriuria is indicated to
reduce the risk of acute cystitis and pyelonephritis in pregnancy
as well as the risk of low birth weight neonates and preterm
infants.
Treatment with antibiotics should be initiated upon diagnosis of

in p e nanc mon the anti iotics that can e sed a e
nit o antoin not o nea te m co amo icla cephale in
ce o ime os om cin and T not on the fi st and thi d
t imeste dependin on the sensiti it es lts o the ine isolate
Duration of treatment will depend on the antibiotics that will be
sed t sho t co se se en da s t eatment is p e e ed o e
sin le dose e imens

ollo p ine c lt e sho ld e done one ee a te
completing the course of treatment.
onito in sho ld e done e e t imeste ntil deli e

Recommendations and Summary of evidence

1. When is asymptomatic bacteriuria in pregnancy diagnosed?
ASB in pregnancy is the presence of >100,000 CFU/mL of
the same uropathogen in two consecutive midstream urine
specimens or ≥100 CFU/mL of a single uropathogen in one
catheterized urine specimen. Symptoms attributable to
urinary infection should be absent.
In settings where obtaining two consecutive urine cultures is

not feasible, or is difficult, one urine culture is an acceptable
alternative for the diagnosis of ASB in pregnancy.

Summary of Evidence
The tas o ce o nd no ne e idence that would merit a change
in the ecommendations om the p e io s ideline In the
update of the Philippine Clinical Practice Guidelines on the Diagnosis
and ana ement o U ina T act In ections in d lts acte i ia
as defined as acte ial co nts o C U m in t o
consec ti e ine specimens ased on in et al Nicolle et al.
in cited ass in hich noted that in o cases in
ce tain as mptomatic o ps a acte ial co nt o C Um
in a midst eam clean catch ine specimen can e confi med a
concomitant co nt in a cathete i ed specimen n the othe hand
lo e acte ial co nts e e not s all confi med the cathete i ed
specimen. A second urine culture for asymptomatic bacteriuria was
done to discriminate between true bacteriuria and contamination. In
the a sence o s mptoms ass in sho ed that the antitati e
th eshold o C U m om midst eam ine o cathete i ed
urine was useful to distinguish true bacteriuria from contamination.
the in esti ato s ha e alidated this th eshold Because these
indi id als e e as mptomatic t o consec ti e c lt es ieldin the
same o anism s om midst eam ine specimens e e needed o
the dia nosis o e e in a ie epo t e al atin the molec la
identit o E. coli isolates o tained in t o consec ti e ine
c lt es om patients ith as mptomatic acte i ia ee lin set
al o nd di e ent coli isolates in se en o them This implied that
nea l hal o the patients ho had een p e io sl classified
as ha in as mptomatic acte i ia e e e in ected ith a di e ent
st ain Th s o tainin t o consec ti e ine c lt es to acc atel
diagnose asymptomatic bacteriuria in pregnant women may not
necessarily identify the etiologic agent.
2. Do all pregnant women have to be screened for asymptomatic

bacteriuria?
Screen ALL pregnant women for asymptomatic
bacteriuria once, between the 9th to 17th week AOG,
preferably on the 16th week AOG.
Summary of Evidence
The Tas o ce o nd no ne e idence that o ld me it a chan e in
the ecommendations om the p e io s ideline
Prevalence of asymptomatic bacteriuria

In a p e alence st d cond cted amon ilipino pregnant women at
a te tia ca e o e nment hospital in anila the o e all p e alence
ate as in omen ith t o consec ti e ine c lt es o e e
eca se onl o the omen in this st d had second c lt es

done a sensiti it anal sis as done. Asymptomatic bacteriuria was
defined as t o ine c lt es sho in si nificant acte i ia o one
es lt sho in si nificant acte i ia in the a sence o a ollo p
c lt e In this second scena io the o e all p e alence ate as
The most common isolates om ilipino p e nant patients
ith definite as mptomatic acte i ia e e sche ichia coli
Klebsiella pneumonia nte ococc s Staphylococcus
saprophyticus Staphylococcus aureus and Klebsiella
ozanae 7
In the same st d the si nificant is acto s associated ith

asymptomatic bacteriuria in pregnant women among those who had
t o ine c lt es e e a e o estation ee s
CI and hemo lo in le els m d
CI I omen ith one ine c lt e onl ee
incl ded the si nificant is acto s on lo istic e ession anal sis
e e a e o estation ee s CI
and histo o UTI CI 7
o ei n
data sho ed that as mptomatic acte i ia occ s in o all
pregnant women and if left untreated can affect both maternal and
etal o tcome The p e alence inc eases amon hi h is p e nant
omen s ch as dia etics and those ith a p e io s histo
o UTI
Benefits
The is o ac i in acte i ia inc eased ith the d ation o
p e nanc hi hest et een the th and th
ee s The th
gestational week appeared to be the optimal time to obtain a single

sc eenin test o acte i ia eca se t eatment i en at this time
o ld p o ide the eatest n m e o acte i ia ee estational
weeks. The two most important complications of untreated
asymptomatic bacteriuriawere acute cystitis and acute pyelonephritis.
etal complications s ch as lo i th ei ht and p ete m
deli e ha e een associated ith as mptomatic acte i ia
3. What is the optimal screening test for asymptomatic bacteriuria

in pregnancy?
A standard urine culture of clean-catch midstream urine is
the test of choice in screening for asymptomatic bacteriuria.
Urinalysis is not recommended as an initial screening test.

Urine dipsticks for leukocyte esterase and/or nitrite tests

are not recommended for screening for asymptomatic
bacteriuria.

In the absence of urine culture, urine gram stain of
uncentrifuged urine (more than one organism per oil
immersion field) is recommended for screening for
asymptomatic bacteriuria in pregnancy.
Summary of Evidence
Urine culture is still the test of choice for detecting asymptomatic
acte i ia in p e nant omen o othe c entl a aila le sc eenin
tests ha e a hi h eno h sensiti it and ne ati e p edicti e al e to
replace the urine culture.
In a ecent desc ipti e c oss sectional st d cond cted in an ladesh

Ullahet al in in esti ated the alidit o fi e sc eenin tests
in p edictin as mptomatic acte i ia in p e nanc a acte ial
co nts pe oil imme sion field in the am stain o ine le oc te
este ase dipstic test c nit ite dipstic test d com ined e oc te
este ase and nit ite dipstic test and e mic oscopic le oc te co nt
pe hi h po e field inal sis compa ed to the old standa d
ine c lt e The st d incl ded p e nant omen and identified
cases o as mptomatic acte i ia The most common isolated
organism was Staphylococcus saprophyticus ollo ed E.
coli Pseudomonas spp. and Klebsiella sp. the fi e sc eenin
tests acte ial co nt pe oil imme sion field o ine am stain had
the hi hest sensiti it and specificit sin a c t o
o o anism I The othe tests sho ed lo e sensiti it and
specificit al es positi e le oc te este ase dipstic test e
as o nd to ha e a elati el hi h sensiti it o t poo
specificit o indicati e o a hi h alse positi e ate Usin a
c to o e inc eased the specificit to t dec eased the
sensiti it to The nit ite dipstic test had a lo sensiti it o
and a specificit o The lo sensiti it o the nit ite
dipstic test ma e d e to its ina ilit to detect non nit ate ed cin
o anisms In this st d the o anism most commonl isolated
was S. saprophyticus hich is not nit ate ed cin I the c ite ion
as ha in eithe o the t o dipstic tests as positi e com inin
the le oc te este ase and the nit ite dipstic tests ielded
sensiti it and specificit o e e i the c ite ion is ha in
oth dipstic tests as positi e then the sensiti it o ld onl e
and the specificit The lo e a ilit o the com ined
positi e test to identi as mptomatic acte i ic p e nant omen
as att i ted to the ina ilit o nit ite dipstic tests to eco ni e non
nit ate ed cin o anisms The the e o e s ested that dipstic
tests ma not e s ita le sc eenin tests o pop lations he e non
nitrate reducing organisms were common or where there was a high
chance o contamination o inal sis on the othe hand le oc te
co nts had a sensiti it o and a specificit o

to its inability to detect non-nitrate reducing organisms. In this study, the organism most commonly isolated was
to its inability to detect
S. saprophyticus which non-nitrate reducing organisms.
is not nitrate-reducing. In this study,
If the criterion the organism
was having either most
of thecommonly isolated
two dipstick testswas
as
S.positive,
saprophyticus
combining the leukocyte esterase and the nitrite dipstick tests yielded 91.7% sensitivity andtests
which is not nitrate-reducing. If the criterion was having either of the two dipstick as
39.2%
The
positive,authors
combining concluded
the leukocyte that
esterase and in the areas
nitrite where
dipstick tests manpower
yielded 91.7% costs
sensitivity
specificity. However, if the criterion is having both dipstick tests as positive, then the sensitivity would only be 25%, and were
39.2%
lospecificity.
and thesspecificity
ch as99.7%.
However, if thean ladesh
criterion
The lower is having ofIndia
ability both thedipstick a positive
tests
combined asistan testand
positive, then epal
the sensitivity
to identify wouldam
asymptomatic only bestain
25%,
bacteriuric
mapregnant ewomen
a p was
and the specificity omisin
99.7%. The lower
attributed cost
to abilityeof ecti e scpositive
the combined
the inability of nitrite eenin
dipstick teststotest
test toidentify oasymptomatic
recognize as mptomatic
non-nitrate bacteriuric
reducing
bacteriuria.
pregnant
organisms.women was attributed
They, therefore, suggestedto that
the dipstick
inabilitytests
of nitrite
may notdipstick testsscreening
be suitable to recognize non-nitrate
tests for populations reducing
where
organisms. They, therefore, suggested that dipstick tests may not be suitable screening
non-nitrate reducing organisms were common or where there was a high chance of contamination. For urinalysis tests for populations where
Another
non-nitrate study
reducing done
organisms were in Argentina
common or where also
there was adoes
high chancenot of support
contamination.
on the other hand, leukocyte counts ≥8/HPF had a sensitivity of 58.3% and a specificity of 80.7%. The authors the
For use
urinalysis
ofon thedipsticks
concluded other
thathand,
in areas
(leukocyte
leukocyte
wherecounts
manpower≥8/HPFesterase
costshadwere
and Bangladesh,
a sensitivity
low, suchofas58.3%
nitrite) for ofscreening
and a specificity
India, Pakistan,80.7%. The authors
and Nepal,
of
gram
as mptomatic
concluded that in areas actemanpower
where i ia in p were
costs e nant low, such omen
as Bangladesh, In India,
this st d andthe
11 Pakistan, Nepal, also
gram
stain may be a promising, cost-effective screening test for asymptomatic bacteriuria. 11
compared chemical
stain may be a promising, dipsticks
cost-effective screeningwithtest forthe urine bacteriuria.
asymptomatic culture as gold standard.
The defined a positi e dipstic es lt as ha in eithe a positi e
Another study done in Argentina also does not support the use of dipsticks (leukocyte esterase and nitrite) for
leAnother
oc te done este ase o alsoa does
positi e nittheate tests o ha in esterase othandtests
nitrite) as
screeningstudy in Argentina not support Inusethisofstudy,
dipsticks
they(leukocyte for
positi
screening eof
of
asymptomatic
The o bacteriuria
asymptomatic nd theinin pregnant
bacteriuria sensitiwomen.
pregnant it o
women. In the
this dipstic
study, they
also compared chemical
also test to
compared e dipsticks
chemical dipsticks
with the urine culture as gold standard. They defined a positive dipstick result as having either a positive leukocyte
with the CI and
urine culture as gold the They
standard. specificit
defined a positive dipstick resultCI as having either a positive leukocyte
esterase or a positive nitrate tests or having both tests as positive. They found the sensitivity of the dipstick test to
esterase or a positive
be 53% (95% CI 48, 58)nitrate tests
and the or having92%
specificity both tests
(95% CI as
91,positive.
93).12 They found the sensitivity of the dipstick test to
be 53% (95% CI 48, 58) and the specificity 92% (95% CI 91, 93).12
Table 7. Computed Likelihood Ratios for the different screening tests
Table 7. Computedwith
compared Likelihood
urineRatiosculture
for the different screening tests compared with urine culture
Table 7. Computed Likelihood Ratios for the different screening tests
Post-test compared with urine culture
Post-test
Positive Negative Post-test Post-test
Screening Positive Negative Probability Probability Sensitivity Specificity
Screening Likelihood Likelihood Probability Probability Sensitivity Specificity
Test Likelihood Likelihood Given a Given a (%)* (%)*
Test Ratio Ratio Given a Given a (%)* (%)*
Ratio Ratio Positive Test Negative Test
Leukocyte esterase (LE) Positive Test Negative Test
Leukocyte
LE + ve esterase 1.44(LE) 0.32 13.75 3.4 87.5 39.2
LE + ve
LE ++ ve 1.44
1.37 0.32
0.79 13.75
10 3.4
7.9 87.5
50.0 39.2
63.5
LE +++
LE ++ veve 1.37
1.62 0.79
0.84 10
15.12 7.9
8.4 50.0
33.3 63.5
79.5
LE +++ (N)
Nitrite ve 1.62 0.84 15.12 8.4 33.3 79.5
NNitrite (N) 97.3 0.71 91.45 7.24 29.2 99.7
N 97.3 0.71 91.45 7.24 29.2 99.7
Combined LE ( +ve) and N
Combined
LE activity LE ( +ve)
1.51and N 0.21 14.24 2.26 91.7 39.2
LE activity 1.51 0.21 14.24 2.26 91.7 39.2
or/and nitrite
or/and
or/and nitrite
nitrite
present
present
present
LE activity 83.3 0.75 90.16 7.6 25.0 99.7
LE activity
and nitrite 83.3 0.75 90.16 7.6 25.0 99.7
and nitrite
present
present count
Leukocytes
Leukocytes
≥ 6/HPF count1.78 0.58 16.37 5.99 62.5 64.9
≥ 6/HPF 1.78 0.58 16.37 5.99 62.5 64.9
≥ 8/HPF 3.02 0.52 24.93 5.41 58.3 80.7
≥≥10/HPF
8/HPF 3.02
2.46 0.52
0.77 24.93
21.29 5.41
7.8 58.3
33.3 80.7
86.5
≥10/HPF
Bacteria count by2.46
Gram staining 0.77 21.29 7.8 33.3 86.5
Bacteria count by
At least 1/OIF 32.75Gram staining 0.085 78.27 0 .92 91.7 97.2
At
At least
least 1/OIF
2/OIF 32.75
95.28 0.085
0.33 78.27
91.28 03.5.92 91.7
66.7 97.2
99.3
At
At least
least 2/OIF
3/OIF 95.28
47.57 0.33
0.67 91.28
83.95 3.5
6.86 66.7
33.3 99.3
99.3
At least 3/OIFand specificity
*Sensitivity 47.57 values 0.67 83.95
were based on the study by Ullah 6.86
201211 33.3 99.3
*Sensitivity and specificity values were based on the study by Ullah 201211

Dipslide culture technique may be used as an alternative
to urine culture in settings where it is available.
Summary of Evidence
An ancillary study done in Argentina assessed the accuracy of
dipslide test and chemical dipsticks (nitrites le oc te este ase o
both) in screening for asymptomatic bacteriuria in pregnancy. They
compared these two modalities with the traditional urine culture as
the old standa d In this st d dipslide had a sensiti it o
CI and a specificit o CI
The positi e li elihood atio o dipslide as CI
and the ne ati e li elihood atio as CI
i en a p etest p o a ilit o a positi e dipslide inc eased
the p o a ilit o ha in acte i ia to and a ne ati e dipslide
dec eased said p o a ilit to less than The a tho s concl ded
that dipslide de ices ma e conside ed as an alte nati e to t aditional
urine cultures.
4. Is treatment indicated for asymptomatic bacteriuria in pregnancy?

Antibiotic treatment for asymptomatic bacteriuria is indicated
to reduce the risk of acute cystitis and pyelonephritis in
pregnancy as well as the risk of low birth weight neonates
and preterm infants.
Summary of Evidence
n pdated Coch ane s stematic e ie o st dies compa in
antibiotic treatment to placebo or no treatment showed that antibiotic
t eatment as e ecti e in clea in acte i ia in as mptomatic
p e nant omen CI acte i ia pe sisted
in o omen ho e e not i en anti iotic t eatment The
di ection o the e ect seen in the di e ent t ials as consistent e en
i the e as a si nificant statistical hete o eneit amon the t ials
This heterogeneity may be explained by differences in study design
and in the definition o a ia les
side om clea in acte i ia anti iotic t eatment as also

associated ith a ed ction in the incidence o p eloneph itis
CI In the nt eated o p the o e all incidence o
p eloneph itis as an in om to The n m e
needed to t eat T to p e ent one episode o p eloneph itis in
p e nant omen ith as mptomatic acte i ia as CI
ed ction in the incidence o p eloneph itis as e pected om
the treatment of asymptomatic bacteriuria.

Antibiotic treatment was also associated with a reduction in the
incidence o lo i th ei ht a ies CI
o e e no di e ence as seen in te ms o the incidence o p ete m
deli e ies nti iotic t eatment as not associated ith ed ction the
incidence o p ete m deli e ies defined as estational a e o less
than ee s CI ased on the th ee
st dies that epo ted this o tcome In one o these th ee st dies the
study only enrolled women with group B streptococcal bacteriuria.
This s stematic e ie desc i ed a o e has a e limitations The e

e e conce ns in te ms o the alit o the st dies incl ded and
some of the research methods were not completely stated. Most of
the st dies also date om the s and s e cept o th ee
and some of the antibiotics used in these studies were no longer
a aila le lso tet ac cline a d sed in one o the st dies as
cont aindicated in p e nanc o e e the es lts seen in this e ie
clea in o acte i ia ed ction o p eloneph itis and ed ction o
incidence of low birth weight babies) were still applicable to other
anti iotics that e e acti e a ainst ina patho ens and e e sa e
to use in pregnancy.
5. Which antibiotics are effective for asymptomatic bacteriuria in

pregnancy?
Treatment with antibiotics should be initiated upon diagnosis
of ASB in pregnancy. Among the antibiotics that can be
used are nitrofurantoin (not for near term), co-amoxiclav,
cephalexin, cefuroxime, fosfomycin, and trimethoprim-
sulfamethoxazole (not on the first and third trimester)
depending on the sensitivity results of the urine isolate.
Summary of Evidence
Compa in di e ent sin le d e imens sed o as mptomatic
acte i ia in p e nanc a Coch ane e ie into et al in
concl ded that no one specific e imen can e ecommended
o e the othe se en tho h anti iotic t eatment as e ecti e in
clea in acte i ia Inc easin anti iotic esistance ho e e
complicated the choice of empiric regimens and was likely to become
an inc easin p o lem i e st dies e e in ol ed in the said e ie
Two of these studies compared cephalosporins (cefuroxime and
cephale in ith anti iotics in p e nanc cate o hich ha e less
association with E. coli resistant strains (fosfomycin trometamol and
pi ampicillin pi mecillinam o si nificant di e ence in e ficac as
noted et een the cephalospo ins and os om cin o pi ampicillin
pi mecillinam nothe st d compa ed t o di e ent eta lactam

anti iotics ampicillin and pi mecillinam oth o these d s e e
Category B drugs. Antibiotic resistance to ampicillin was increasing
hile pi mecillinam still had ood acti it a ainst E. coli. There was
no si nificant di e ence in the e ect o eithe d on pe sistent
in ection o ec ent in ection o e e pi mecillinam as
associated ith a hi he incidence o omitin in p e nant omen
i en the d nothe st d hich as pa t o the said Coch ane
e ie compa ed nit o antoin i en o one da s nit o antoin
i en o se en da s it o antoin as sed eca se the e as
less reported antibacterial resistance related to its use compared with
othe anti iotics li e penicillins o T The e as no si nificant
di e ence in s mptomatic in ections incidence o p ete m deli e ies
and tole ance o s ects o e e mo e t eatment ail es e e
seen in patients t eated o onl one da s estin that the lon e
t eatment d ation se en da s o nit o antoin as p e e a le
6. What is the duration of treatment for asymptomatic

bacteriuria in pregnancy?
Duration of treatment will depend on the antibiotics that
will be used, but, short-course (seven days) treatment
is preferred over single-dose regimens.
Summary of Evidence
The a tho s o a Coch ane s stematic e ie o CTs compa in
a single dose regimen for asymptomatic bacteriuria in pregnancy with
a sho t d ation e imen o to se en da s concl ded that the o
to se en da t eatment e imen ma e p e e a le o e the one
day treatment regimen. In the most recent update of this systematic
e ie p lished in th ee ne t ials e e incl ded ne st d
compa ed a sin le dose o os om cin t ometamol ith a fi e da
co se o ce o ime a et l The o tcomes meas ed e e
cure rates and side effects. The second study compared a single
dose o os om cin ith a se en da co se o amo icillin cla lanate
The o nd no di e ence et een the t o o ps in te ms
o c e ec ences and pe sistence The thi d st d incl ded in
this e ie compa ed t o di e ent dosin e imens o nit o antoin
dosin e imens one da s se en da e imen It
sho ed a si nificantl hi he c e ate in omen i en the se en
da e imen ch o the data o the meta anal sis came om this
study. The authors concluded that longer duration of treatment may
e mo e e ecti e than sin le dose ho e e lon e e imens ma
present with concerns on compliance.

Table 8. Antibiotics that can be used for asymptomatic bacteriuria in
pregnancy
Antibiotics Recommended dose and duration FDA Risk Category
Cephalexin 500 mg BID for 7 days B
Cefuroxime axetyl 500 mg BID for 7 days B
Fosfomycintrometamol 3 g in a single dose B
Amoxicillin-clavulanate 625mg BID for 7 days B
Cefuroxime 500mg BID for 7 days B
Nitrofurantoinmacrocrystal 100 mg QID for 7 days; B (May cause
100 mg BID for monohydrate/ hemolyticanemia,
macrocrystal (not available locally) anophthalmia, hypoplastic
for 7 days left heart syndrome, ASD,
cleft lip and palate. May
be given on the second
trimester of pregnancy until
32 weeks AOG. Use in the
first trimester of pregnancy
is appropriate when no
other suitable alternative
antibiotics are available)
TMP-SMX 160/800 mg BID for seven days C (avoid in 1st and 3rd
trimester)
A follow up urine culture should be done one week after

completing the course of treatment.
Summary of Evidence
The Tas o ce o nd no ne e idence that o ld me it a chan e in
the ecommendations om the p e io s idelines
Monitoring should be done every trimester until delivery.


Algorithm 4. Alternative diagnostic evaluation for asympto-
matic bacteriuria in settings where urine culture
is not available
Pregnant patient
on pre-natal check-up
YES POSITIVE
Urine C/S available? Urine C/S Treat as ASB
NEGATIVE
NO
No ASB
Dipslide culture YES POSITIVE

Dipslide culture Treat as ASB
available?
NEGATIVE
NO No ASB
POSITIVE
Do Gram Stain Treat as ASB
NEGATIVE
No ASB

References
in hapi o d ioce T a is tamm ene al idelines
o the e al ation o ne anti in ecti e d s o the t eatment o ina t act
in ection Clin In ect is ppl
icolle adle Col an ice C chae e ooton T In ectio s
iseases ociet o me ica idelines o the ia nosis and T eatment o
s mptomatic acte i ia in d lts Clin In ect is
ass s mptomatic in ections o the ina t act T ans ssoc m h s
a tlett C alen edicti e al e o ine c lt e m Clin athol
latt antitati e definition o acte i ia m ed

ee lin s o e C aast a oepelman I Is a second ine
specimen necessary for the diagnosis of asymptomatic bacteriuria? A Brief
epo t Clin In ect is
escon I a in alao olina casiano aniel analastas
e alence o as mptomatic acte i ia and associated is acto s in p e nant
omen hil ic o iol In ect is
olan e le mit o don a id s mptomatic acte i ia
in no mal and hi h is p e nanc stet ne and ep od iol
ten ist ahlen ilsson I ichin anson acte emia in p e nanc m

pidemiol
nd eole T atte son T pidemiolo nat al histo and mana ement o
ina t act in ections in p e nanc ed Clin o th m
Ullah a man hmed I alam s mptomatic acte i ia in p e nant
mothe s a alid and cost e ecti e sc eenin test in an ladesh o nal o
o stet ics and naecolo Inte net an cited ct
i nini Ca oli alos idme cc ac o ia nostic Tests to etect
s mptomatic acte i ia in e nanc stet necol
maill a e C nti iotics o as mptomatic acte i ia in p e nanc

Coch ane ata ase o stematic e ie s C
into T e ia estin o s ell T i e ent anti iotic e imens
for treating asymptomatic bacteriuria in pregnancy. Cochrane Database of
stematic e ie s C
idme lme o l i nini o anti ation o t eatment o
as mptomatic acte i ia d in p e nanc Coch ane ata ase o stematic
e ie s C

ACUTE CYSTITIS IN PREGNANCY
Section Summary
efinition
In an othe ise health p e nant oman ac te c stitis in
p e nanc is cha acte i ed ina e enc enc
d s ia and acte i ia itho t e e and costo e te al an le
tenderness. Gross hematuria may also be present.
e t eatment dia nostic tests

In p e nant omen s spected to ha e UC o tain a p e
t eatment ine c lt e and sensiti it test o a midst eam clean
catch urine specimen.
In the a sence o a ine c lt e the la o ato dia nosis o

ac te c stitis can e dete mined
a The p esence o si nificant p ia defined as
p s cells mm o ncent i ed ine
p s cells o cent i ed ine
AND
positi e le oc te este ase and nit ite test on dipstic
Treatment of acute cystitis in pregnancy should be instituted
immediatel to p e ent the sp ead o the in ection to the idne
ince E. coli emains to e the most common o anism isolated

anti iotics to hich this o anism is most sensiti e and hich a e
sa e to i e d in p e nanc sho ld e sed
se en da t eatment ith an o al antimic o ial a ent that is

safe for use in pregnancy is recommended; except for fosfomycin
hich is i en as a sin le dose
Strong recommendation, Low level of evidence
In the a sence o a ine c lt e and sensiti it empi ic the ap

should be based on local susceptibility patterns of uropathogens.
nti iotic esistance ased on c lt e and sensiti it

I the patient is clinicall espondin to the p esent t eatment
the e is no need to e ise the anti iotic i esistance to the
empirically started antibiotic is reported on urine culture. Adjust
anti iotic the ap ased on ine c lt e es lts hen

the e is no imp o ement in the clinical signs and symptoms and
la o ato es lts o hen the e is o senin o the patient s
condition.

ost t eatment ine c lt e one to t o ee s a te completion o
the ap sho ld e o tained to confi m e adication o acte i ia
and resolution of infection in pregnant women.
e nant patients ith p eloneph itis ec ent UTIs conc ent

estational conc ent neph olithiasis o olithiasis and
p e eclampsia sho ld e monito ed at monthl inte als ntil
deli e to ens e that ine emains ste ile d in p e nanc

1. When do you suspect acute cystitis in pregnancy?
In an otherwise healthy, pregnant woman, acute cystitis in
pregnancy is characterized by urinary frequency, urgency,
dysuria, and bacteriuria without fever and costovertebral
angle tenderness. Gross hematuria may also be present.
Summary of Evidence
The pdate o the I Tas o ce on UTI s definition o
acute cystitis in pregnancy was based on clinical symptoms such as
d s ia e ent ination and lo e a dominal o s p ap ic pain
itho t e e
2. Is a pre-treatment diagnostic test required in acute cystitis in

pregnancy?
In pregnant women suspected to have acute uncomplicated
cystitis, obtain a pre-treatment urine culture and sensitivity
test of a midstream clean catch urine specimen.
In the absence of a urine culture, the laboratory

diagnosis of acute cystitis can be determined by:
a) The presence of significant pyuria defined as:
• ≥ 8 pus cells/mm3 of uncentrifuged urine, OR
• ≥ 5 pus cells/HPF of centrifuged urine
AND
b) A positive leukocyte esterase and nitrite test on dipstick.

Summary of Evidence
The physiologic changes during pregnancy like increased
ph siolo ical a inal discha e inc eased la it o pel ic tiss es
and the discomfort due to an enlarging abdominal mass makes it
impo tant to confi m the dia nosis o UTI The dia nosis sho ld e
confi med so that nnecessa e pos e o the et s to antimic o ial
a ents ma e a oided c oss sectional st d c ead et al
in noted the tilit o ine sediment mic oscop in the initial
e al ation o p e nant omen ith s mptomatic UTI In this st d
the o nd that ine sediment mic oscop ith c t o o epithelial
cells and C had a sensiti it o specificit o
o and o It also had a post test p o a ilit o
i mic oscop as positi e
3. What is the treatment for acute cystitis in pregnancy?

Treatment of acute cystitis in pregnancy should be
instituted immediately to prevent the spread of the
infection to the kidney.
Since E. coli remains to be the most common organism

isolated, antibiotics to which this organism is most
sensitive and which are safe to give during pregnancy
should be used.
A seven-day treatment with an oral antimicrobial agent

that is safe for use in pregnancy is recommended;
except for fosfomycin which is given as a single dose.
In the absence of a urine culture and sensitivity, empiric

therapy should be based on local susceptibility patterns
of uropathogens.
Summary of Evidence
The incidence o ac te c stitis d in p e nanc as
Infection occurs during the second trimester and may not necessarily
e p eceded as mptomatic acte i ia d in the p e io s ee s
In UTI in p e nanc the el a e o oth the mothe and the et s a e
at sta e ma in t eatment ail e o e en incomplete esponse less
acceptable.

There was limited data assessing the superiority of one antibacterial
e imen o e anothe in te ms o e ficac patient compliance and
sa et d in p e nanc Coch ane e ie o CTs on anti iotics
for the treatment of symptomatic UTIs in pregnancy could not show
that one t eatment e imen as ette than anothe ates o c e
e e hi h and the e e e e e complications 7 et ospecti e
case cont ol st d in esti atin the association et een anti acte ial
se and i th de ects o nd that cephalospo ins e th om cins and
penicillins e e elati el sa e to se in p e nanc n the othe hand
major birth defects were noted to be associated with women who
too s l onamides and nit o antoins the st dies on the sa et
p ofile o nit o antoin and s l onamides e e needed The data on
inolones s ested an inc eased association ith ca diac de ects
Quinolones were not recommended to be used in pregnancyunless
the e a e o e idin easons o thei se ince this st d as a
et ospecti e case cont ol st d it as s ect to ce tain iases
incl din ecall ias selection ias and the p esence o con o ndin
factors such as the underlying infection for which the antibiotic was
used. o e st dies a e needed to the in esti ate these epo ted
associations.
mpi ic se o co amo icla o p ete m la o ith pt e o

membranes was associated with an increased risk of neonatal
nec oti in ente ocolitis This ma e e plained the dis ptions
in the mic o ial coloni ation o the neonatal t lo i lence
mic o o a allo in s se ent coloni ation mo e i lent mic o
organisms following birth. Another explanation could be the ability of
the immat e t to a so e oto ins completel leadin to m cosal
damage which could lead to C

Table 9. Antibiotics that can be used for acute cystitis in pregnancy
Antibiotics Recommended Dose Pregnancy Birth Defects Comments/ Qualifiers
and Duration Category / Neonatal
Complications
Cephalexin 500 mg QID for 7 days B None Safe to use in any trimester
Cefadroxil 1 g BID for 7 days B None Safe to use in any trimester
Cefuroxime 500mg BID for 7 days B None Safe to use in any trimester
Cefaclor 500mg TID for 7 days B None Safe to use in any trimester
Cefixime 200mg BID for 7 days B None Safe to use in any trimester
Cefpodoxime 100mg BID for 7 days B None Safe to use in any trimester
Nitrofurantoin 100 mg QID for 7 days B Hemolyticanemia, May be given on the second
for macrocrystals anophthalmia, trimester of pregnancy until
100 mg BID for hypoplastic left heart 32 weeks AOG. Use in the
monohydrate/ syndrome, ASD, cleft first trimester of pregnancy
macrocrystals (not lip and palate8 is appropriate when no
available locally) other suitable alternative
antibiotics are available.
Fosfomycin 3 g single dose B None Safe to use in any trimester
trometamol
Pivmecillinam 400 mg BID for 7 days B None Safe to use in any trimester
Amoxicillin- 625mg BID for 7 days Neonatal necrotizing Avoid in women at risk of
clavulanate enterocolitis10 preterm labor10
TMP-SMX 160/800 mg BID for C Anencephaly, May be given on the second
7 days hypoplastic left heart and third trimester of
syndrome, choanal pregnancy.
atresia, transverse Use in the first trimester of
limb defect, pregnancy is appropriate
diaphragmatic when no other suitable
hernia8 alternative antibiotics are
available.
*Use only for culture- proven
susceptible uropathogens
due to high prevalence
of local resistance.
4. In clinically improving patients whose urine culture result shows

an organism resistant to the empirically started antibiotic, should
the antibiotic be changed based on the susceptibility report?
If the patient is clinically responding to the present treatment,
there is no need to revise the antibiotic if resistance to the
empirically started antibiotic is reported on urine culture.
Adjust antibiotic therapy based on urine culture results
ONLY when there is no improvement in the clinical signs
and symptoms and laboratory results or when there is
worsening of the patient’s condition.

Summary of Evidence
The e e e no st dies add essin this specific issue. Because of
the higher likelihood of antimicrobial resistance or of a suboptimal
t eatment esponse in a p e nant oman compa ed ith a non
p e nant oman and the ad e se conse ences to the et s i
t eatment ails o i t eatment esponse is dela ed o incomplete
the C I clinical ideline ecommended that anti iotic
the ap e modified ased on the es lts o c lt e and sensiti it
tests. o e e clinical and acte iolo ic c es e e o ten achie ed
e en hen the o anisms e e esistant in it o to the selected a ent
th s a chan e in anti iotic the ap as not mandato so lon as the
patient as espondin clinicall as o se ed the ph sician The
consensus of our expert panel is that there is no need to shift the
anti iotics i the patient is clinicall espondin o e e clea ance
of bacteriuria should be documented at the end of antibiotic therapy
lease see ecommendation e a din epeat c lt es elo o
patients ho a e not espondin clinicall anti iotic t eatment sho ld
definitel e modified ased on c lt e and sensiti it es lts
5. What is the clinical utility of a post-treatment urine culture?

Post-treatment urine culture one to two weeks after
completion of therapy should be obtained to confirm
eradication of bacteriuria and resolution of infection in
pregnant women.
Pregnant patients with pyelonephritis, recurrent UTIs,

concurrent gestational DM, concurrent nephrolithiasis
or urolithiasis, and pre-eclampsia, should be monitored
at monthly intervals until delivery to ensure that urine
remains sterile during pregnancy.
Summary of Evidence
e nant omen ho ha e had a acte i ic episode d in the
p e nanc ma e i e close monito in eca se the ha e an
increased risk for repeated episodes of bacteriuria during the
course of the pregnancy. e nant omen ma p esent ith se e e
pyelonephritis. Pyelonephritis could also lead to other conditions such
as p emat e la o etal dist ess s nd ome shoc disseminated
int a asc la coa lation and death Th s it is c itical that acte i ia
be eradicated and documented through urine cultures.
The e as no e idence e a din the e enc o monito in o

ec ence o in p e nant omen e ie in et al

s ested clinic ollo p ithin t o weeks after acute therapy of
acute pyelonephritis during which a urine culture was obtained as a
test o c e In st dies on t eatment o in p e nanc ollo p
c lt es e e done on the th th da post t eatment
The e is no e idence to s ppo t optimal timin o epeat ine c lt es

during the rest of pregnancy. Acute pyelonephritis tends to occur in
the latte sta es o p e nanc s all in the last t imeste
e nant patients at hi h is o de elopin ac te c stitis o

acute pyelonephritis are discussed in the section on asymptomatic
bacteriuria in pregnancy.
References
a is c te ina t act in ections and s se ent p o lems Clin stet
ne
Infectious Disease. The Philippine Clinical Practice Guidelines on the Diagnosis
and ana ement o U ina T act In ections In d lts Update e on
Cit hilippines I hilippine ociet o ic o iolo and In ectio s
iseases
ohnson tapleton T a tne e on a o enstein nn
U ina T act In ection Inte net C ma t edicine aila le om
http sma tmedicine acponline o content asp osId
c ead thie an n shle Tan imanpana a ilapai n en
et al ia nostic and T eatment i fic lties o eloneph itis in e nanc in
eso ce imited ettin s m T op ed
a is ilst ap III C stitis d in p e nanc a distant clinical entit
C stitis d in p e nanc a distant clinical entit
ohnson tapleton T a tne U ina T act In ection C h sicians
In o mation and d cation eso ce Inte net aila le om http pie
acponline o ph sicians diseases d d html
a e C alos T eatments o s mptomatic ina t act in ections
d in p e nanc e ie Coch ane ata ase o stemic e ie s I
C
C ide Cle es ee h is e o s C nti acte ial
edication Use in e nanc and is o i th e ects ational i th
e ects e ention t d ch ediat dolesc ed
l onamides it o antoin and is o i th e ects Committee pinion
o me ican Colle e o stet icians and necolo ists stet necol
en on Ta lo Ta no o di oad spect m anti iotics o p ete m

p ela o pt e o etal mem anes the C I andomised t ial The
ancet Inte net a aila le om http lin in h
else ie com et ie e pii
ohnson U ina t act in ection ie clinical idance om C Inte net
aila le om http pie acponline
in a e e illa imited clinical tilit o lood and ine

cultures in the treatment of acute pyelonephritis during pregnancy. Am J Obstet
necol
illa in a l tpatient t eatment o p eloneph itis in p e nanc
a andomi ed cont olled t ial stet necol
in ende shott C e e illa andomi ed t ial o th ee
antibiotic regimens for the treatment of pyelonephritis in pregnancy. Obstet
necol
in ende shott C e e illa tpatient t eatment o ac te
p eloneph itis in p e nanc a te ee s stet necol
nin C eloneph itis ie clinical idance om C Inte net aila le
om http pie acponline.

ACUTE UNCOMPLICATED PYELONEPHRITIS IN PREGNANCY
Section Summary
efinition
The classic syndrome of AUP in healthy adult women is also
applied to p e nant omen U is cha acte i ed e e
T C chills an pain costo e te al an le tende ness
na sea and omitin ith o itho t si ns and s mptoms o
lo e ina t act in ection a o ato findin s incl de p ia
C o cent i ed ine on inal sis and acte i ia
ith co nts o C U m on ine c lt e
Diagnostic tests
Urinalysis and Gram stain are recommended.
U ine c lt e and sensiti it test sho ld also e pe o med

o tinel to acilitate cost e ecti e se o antimic o ial a ents and
eca se o the potential o se io s se elae i an inapp op iate
antimicrobial agent is used.
Blood cultures are NOT routinely recommended except in

patients with signs of sepsis.
o tine enal lt aso nd is o limited clinical enefit and sho ld

e ese ed o omen ho ail to espond to initial t eatment
Indications for admission

The ollo in a e conside ed as indications o admission
Ina ilit to maintain o al h d ation o ta e medications
Conce n a o t compliance
esence o possi le complicatin co mo id conditions
e e e illness ith hi h e e se e e pain ma ed de ilit
i ns o p ete m la o
i ns o sepsis
In the a sence o a ine c lt e and sensiti it empi ic the ap
should be based on local susceptibility patterns of uropathogens.
ince E. coli emains to e the most common o anism isolated

anti iotics to hich this o anism is most sensiti e and hich a e
sa e to i e d in p e nanc sho ld e sed
The ecommended d ation o t eatment is da s

ost t eatment ine c lt e sho ld e o tained a te completion
o anti iotic t eatment to confi m esol tion o the in ection
test o c e The patient sho ld e ollo ed p o s mptoms
of recurrent infection and monthly urine cultures should be
pe o med ntil deli e
ec ence o mptoms
ec ence o s mptoms e i es anti iotic t eatment ased on
ine c lt e and sensiti it test es lts in addition to assessin
for underlying genitourologic abnormalities.
The d ation o e t eatment in the a sence o a olo ic

o patients hose s mptoms ec and hose c lt e sho s

the same o anism as the initial in ectin o anism a o to
si ee e imen is ecommended
e ention o ec ent UTI in p e nanc

o pha macolo ic inte ention has een p o en to e e ecti e in
the p e ention o ec ent UTI in p e nanc
on pha macolo ic inte ention in the o m o close s eillance

ollo p ith ine c lt es e e t o ee s ntil ee s
has een p o en to e non in e io to nit o antoin in p e entin
recurrent symptomatic UTI in pregnancy.
C an e ice is not ecommended in the p e ention o UTI as it

does not reduce asymptomatic bacteriuria and recurrence of UTI
in pregnant women.

hen is ac te ncomplicated p eloneph itis in p e nanc
suspected?
The classic syndrome of AUP in healthy adult women is
also applied to p e nant omen U is cha acte i ed
e e T C chills an pain costo e te al an le
tende ness na sea and omitin ith o itho t si ns
and s mptoms o lo e ina t act in ection a o ato
findin s incl de p ia C o cent i ed ine
on inal sis and acte i ia ith co nts o C U
m on ine c lt e
Summary of Evidence
In a et ospecti e ea pop lation ased st d o sin leton
deli e ies the incidence o antenatal p eloneph itis as o nd to e
hich as lo e than the mentioned c ead et
al as epo ted in antepa t m ni e sal sc eenin desc i ed in ea lie
literature. The most common s mptom epo ted as costo e te al
an le tende ness the s mptoms incl de headache i o s o chills
ano e ia na sea d s ia m scle pain and omitin Independent
risk factors associated with acute antepartum pyelonephritis were
n llipa it CI p p e io s histo o
ina t act in ection CI p and
o n e mate nal a e CI p
ased on cases epo ted in t o t o ea lon it dinal st dies ill
et al in and by McGready et al. in the occ ence o
p eloneph itis as noted to e hi hest in the second t imeste
o cases occ ed in the second t imeste
2. What are the recommended diagnostic tests for acute

uncomplicated pyelonephritis in pregnancy?
Urinalysis and Gram stain are recommended.
Urine culture and sensitivity test should also be performed

routinely to facilitate cost-effective use of antimicrobial
agents and because of the potential for serious sequelae if
an inappropriate antimicrobial agent is used.
Blood cultures are NOT routinely recommended except

in patients with signs of sepsis.

Routine renal ultrasound is of limited clinical benefit
and should be reserved for women who fail to respond
to initial treatment.
Summary of Evidence
Urinalysis
The e as hi he sensiti it and ne ati e p edicti e al es o ine
sediment mic oscop inal sis o e ine dipstic test ith a
ne ati e post test p o a ilit o amon p e nant omen ith
acute pyelonephritis. o e e d e to the st d s limited sample
si e and the test s inte o se e a ia ilit these es lts sho ld still
e ie ed ith ca tion
There is no new data directly comparing different diagnostic tests for

antenatal pyelonephritis.
Blood culture
The p e io s idelines cited in et al. wherein data was pooled
om th ee andomi ed cont olled t ials that incl ded p e nant
women with pyelonephritis.7 U ine and lood c lt e
es lts e e co elated ith clinical mana ement decisions
o tcome len th o hospital sta and cost In this st d onl
o the pa ticipants e i ed chan es om initial anti iotic the ap
ost anti iotic chan es e e made eca se o a pe cei ed lac o
esponse to t eatment athe than ased on c lt e and sensiti it
es lts nl in o o the cases as the initial anti iotic e imen
chan ed solel eca se o acte emia despite ade ate esponse to
the initial treatment with ceftriaxone. The reasons for initial antibiotic
chan es e e pe sistent e e pe sistent costo e te al
an le tende ness le oc tosis ith C co nt
cells mm ec ent p eloneph itis si ns o sepsis
pe sistent tempe at e ele ation and acte emia and
pe sistent tempe at e ele ation and C tende ness lood
c lt e es lts di ectl in enced mana ement p olon in the
d ation o hospitali ation eca se omen ith acte emia e e
hospitali ed o a mean o da s da s hile those itho t
acte emia e e confined o a mean o da s da s
p despite simila clinical o tcomes.7
Renal ultrasound
et ospecti e e ie o hospital eco ds o p e nant omen
dia nosed ith p eloneph itis admitted o e a se en ea pe iod
sho ed limited enefit o enal lt asono aph o p e nant omen

ith p eloneph itis the omen hose eco ds e e e ie ed
se ent fi e nde ent enal lt asono aph T ent si o
them had no mal es lts ild enal pel is dilatation to
mm as noted in patients mode ate dilatation
to mm in patients and se e e dilatation mm
in patients the noted a no malities e e d plicated
collectin s stems and enal calc li each o hich as o nd in t o
cases ll the patients e e t eated ith anti iotics U ete al
stents were not necessary. Comparing women who underwent renal
lt asono aph to those ho did not the o nd no di e ence in
maternal characteristics or pregnancy outcomes. Because renal
lt asono aph a el a ected mana ement and did not si nificantl
a ect p e nanc o tcomes its se is o limited al e in p e nant
women with pyelonephritis.
3. What are the indications for admission in patients with acute

uncomplicated pyelonephritis in pregnancy?
The following are considered as indications for admission:
• Inability to maintain oral hydration or take medications;
• Concern about compliance;
• Presence of possible complicating (co-morbid)
conditions;
• Severe illness with high fever, severe pain, marked
debility;
• Signs of preterm labor;
• Signs of sepsis.
Summary of Evidence
In a Coch ane s stematic e ie done in the did a meta
anal sis o th ee CTs n p e nant omen compa in
o tpatient s inpatient mana ement o patients ith antenatal
ac te p eloneph itis e ond ee s estation It as sho n that
outpatient therapy was not inferior to inpatient with respect to clinical
and acte iolo ic c e to da s a te initiation o the ap ith
an o CI cl ded in these t ials e e
patients unable to maintain oral hydration or take medications; cases
where there was concern about compliance; presence of possible
complicatin co mo id conditions se e e illness ith hi h e e
se e e pain ma ed de ilit si ns o p ete m la o and si ns o sepsis
indications o admission stated in the p e io s ecommendation
eca se most patients ho ha e p eloneph itis a e deh d ated

initial management should include IV hydration and urine output
monito in o app op iate candidates o o t patient the ap an

initial o se ation pe iod o ho s is needed to confi m mate nal
and etal ell ein in this time antimic o ial the ap h d ation
and la o ato e al ation is initiated Upon discha e inst ctions
sho ld e i en to et n to the eme enc oom immediatel i
si ns o sepsis espi ato ins ficienc o p ete m la o de elop
T ent o ho s a te discha e patient sho ld e e al ated o
appropriate clinical response.
4. What drugs can be used for empiric treatment of acute

In the absence of a urine culture and sensitivity, empiric
therapy should be based on local susceptibility patterns
of uropathogens. Since E. coli remains to be the most
common organism isolated, antibiotics to which this
organism is most sensitive and which are safe to give
during pregnancy should be used.
Summary of Evidence
The e e e no andomi ed clinical t ials on t eatment o ac te
antenatal pyelonephritis alone. All of the studies included healthy
non p e nant emales males and complicated UTI ee mma
o idence o UC in e nanc
There was limited data that assessed the superiority of one

anti acte ial e imen o e anothe in te ms o e ficac patient
compliance and sa et d in p e nanc Coch ane e ie o CTs
on antibiotics for the treatment of symptomatic UTIs in pregnancy was
not able to show that one treatment regimen was better than another.
ates o c e e e hi h and the e e e e e complications
Cephalospo ins e th om cins and penicillins e e elati el sa e
to se in p e nanc n the othe hand ma o i th de ects e e
associated with women who took sulfonamides and nitrofurantoin.
the st dies on the sa et p ofile o nit o antoin and s l onamides
were needed. Quinolones may be associated with an increased risk
o ca diac de ects t p esent inolones a e not ecommended o
se in p e nant omen nless the e a e o e idin easons o thei
use.
The st d o C ide et al in on the elationship et een

anti iotics and i th de ects e e o nd to ha e se e al limitations
i st the e is the possi ilit o ecall ias eca se the espondents
e e inte ie ed om ee s to ea s a te the p e nanc and
the anti iotic p esc i ed as not confi med medical eco ds lso
since this as a et ospecti e c oss sectional o se ational st d

relatively safe to use in pregnancy. On the other hand, major birth defects were associated with women who took
sulfonamides and nitrofurantoin. Further studies on the safety profile of nitrofurantoin and sulfonamides were
needed. Quinolones may be associated with an increased risk of cardiac defects. At present, quinolones are not
recommended for use in pregnant women unless there are overriding reasons for their use.10
only associations could be made. There were also confounding factors
The
s ch studyasof Crider
the etinal.ection
in 2009 on othe relationship
hich the between
antiantibiotics
iotic andas birthpdefects
esc were
i ed found tohich
have
could also account for the birth defects noted.
several limitations. First, there is the possibility of recall bias because the respondentsIn a Committee6
were interviewed from
weekspinion o after
to 2 years thethe me icanandColle
pregnancy, e o prescribed
the antibiotic stetwasics not and
confirmed bynecolo
medical records. theAlso,
saidthisthat
since enefits and
was a retrospective is s observational
cross-sectional, incl dinstudy, potential o could
only associations te ato enesis
be made. o
There were
o confounding
also mate nal adsuch
factors e assethe infection
eactions for whichotheantiantibioticiotics p escwhich
was prescribed, i ed couldsho ld for
also account e
conside ed and 10,11
disc ssed ith patients especiall
the birth defects noted. In a Committee Opinion of the American College of Obstetrics and Gynecology, theyo anti iotics
p esc
said i ed and
that benefits in risks
the fi st potential
(including t imeste I theor eof maternal
for teratogenesis e e adverse
no othe
reactions) sof antibiotics
ita le
anti iotics a aila le s l onamides o nit o antoin ma
prescribed should be considered and discussed with patients, especially for antibiotics prescribed in the first still e
conside ed as possi le anti iotic choices d in the fi st
trimester. If there were no other suitable antibiotics available, sulfonamides or nitrofurantoin may still be t imeste
aid anti
considered iotics
as possible ma choices
antibiotic also still
during e trimester.
the first sed Said as antibiotics
fi st line a ents
may also o asthe
still be used first-
tlineeatment and p e ention o UTI in the second
agents for the treatment and prevention of UTI in the second and third trimesters. and thi
11 d t imeste s
Table 10. Empiric treatment regimens for acute uncomplicated pyelonephritis

in pregnant
Table womenregimens for acute uncomplicated pyelonephritis in pregnant women
10. Empiric treatment
Antibiotic Dose, Frequency and Duration Category
PARENTERAL (given until patient is afebrile)
Primary Ceftriaxone 1-2 g IV q 24 hours B
Cefotaxime 1 -2 g IV q 8 hours B
Ceftazidime 2 g IV q 8 hours B
Alternative Ampicillin-sulbactam (when GS shows 1.5 g IV q6 hours B
gram-positive organisms)
Reserved Piperacillin-tazobactam 2.25 g IV to 4.5 g IV q 6-8 hours B
ORAL (given when patient is 48 hours afebrile and based the parenteral medication given and/or sensitivity results)
see comments and qualifiers under AUC in pregnancy
Cephalexin 500 mg QID to complete 14 days B
Cefadroxil 1 g BID to complete 14 days B
Cefuroxime axetyl 500mg BID to complete 14 days B
Cefaclor 500mg TID to complete 14 days B
Cefixime 200mg BID to complete 14 days B
Cefpodoximeproxetil 100 mg BID to complete 14 days B
Amoxicillin-clavulanate
Guidelines on Diagnosis and625mg BID to ofcomplete
Management 14 days
UTI in Adults 2013 Update PartB1 52
5.5.What
Whatis the is the duration
effective effective duration
of treatment of treatment for AUP?
for AUP?
Summary of Evidence
Summary of Evidence
Int a eno s antimic o ial the ap is s all contin ed ntil the
Intravenous antimicrobial therapy is usually continued until the patient is afebrile for 48 hours and symptoms have
patient is a e ile o ho s and s mptoms ha e imp o ed e o e
improved
s itchin beforetoswitching
an otoalan oral regimen totocomplete
e imen completea total a
of 14 days otherapy. da
total If thespatient
the apfails to
respond clinically within 72 hours, further evaluation should be done to investigate for the presence of
antibiotic resistance, urolithiasis, perinephric abscess formation or urinary tract abnormalities. The antibacterial
regimen should be modified based on urine culture/sensitivity results.
I the patient ails to espond clinicall ithin ho s the
e al ation sho ld e done to in estigate for the presence of antibiotic
esistance olithiasis pe ineph ic a scess o mation o ina t act
a no malities The anti acte ial e imen sho ld e modified ased
on ine c lt e sensiti it es lts
The e as no lite at e o nd sho in s pe io it o da co se

o t eatment o e sho te d ation o teen da co se o t eatment
was based on expert consensus.
6. What is the clinical utility of a post-treatment urine culture in

acute pyelonephritis in pregnancy?
Post-treatment urine culture should be obtained after
completion of antibiotic treatment to confirm resolution of
the infection (“test of cure”). The patient should be followed
up for symptoms of recurrent infection and monthly urine
cultures should be performed until delivery.
Summary of Evidence
lease e e to the section on post t eatment ine c lt e in Acute
Cystitis in Pregnancy.
7. What is the recommended management for patients whose

symptoms recur?
Recurrence of symptoms requires antibiotic treatment based
on urine culture and sensitivity test results, in addition to
assessing for underlying genitourologic abnormalities.
The duration of re-treatment in the absence of a urologic

For patients whose symptoms recur and whose culture

shows the same organism as the initial infecting
organism, a four to six-week regimen is recommended.
These recommendations were based on expert opinion. There was

sca cit o e idence e a din d ation o mana ement o ec ent
urinary tract infections in pregnancy.

8. How can recurrent UTI in pregnancy be prevented?
No pharmacologic intervention has been proven to be
effective in the prevention of recurrent UTI in pregnancy.
Non-pharmacologic intervention in the form of close

surveillance (follow-up with urine cultures every two
weeks until 36 weeks) has been proven to be non-inferior
to nitrofurantoin in preventing recurrent symptomatic
UTI in pregnancy.
Cranberry juice is not recommended in the prevention

of UTI as it does not reduce asymptomatic bacteriuria
and recurrence of UTI in pregnant women.
Summary of Evidence
In a Coch ane e ie o a andomi ed cont olled t ial compa in dail
nit o antoin pl s close s eillance ith close s eillance alone
o ec ent UTI in p e nanc the e as no si nificant di e ence
between the two groups in terms of reduction of recurrent UTI.
o e e the did see a si nificant ed ction o in patients i en
dail nit o antoin pl s close s eillance ote this o tcome as
epo ted o patients ho had attendance d in ollo p
The se o nit o antoin m o all th ee times da ith close

s eillance ollo p e e t o ee s ntil ee s as sho n
to e a possi le inte ention o the ed ction o in p e nanc
but not in the reduction of recurrent urinary tract infection.
C an e ice coc tail m ltiple dail dosin sho ed ed ction

in incidence ate atio CI and
ed ction in all UTI incidence ate atio CI
ho e e oth e e statisticall not si nificant the mo e the
most common cause of drop out in this study was gastrointestinal
upset in the groups initially taking three doses of cranberry juice.

References
a is c te ina t act in ections and s se ent p o lems Clin stet
ne
o e ts antitati e ine c lt e in patients ith ina t act in ection and
acte emia m Clin athol
in hapi o d ioce T a is tamm ene al idelines
o the e al ation o ne anti in ecti e d s o the t eatment o ina t act
in ection Clin In ect is ppl
a ash eint a e ien o i nit e lotni heine c te
antepa t m p eloneph itis in p e nanc a c itical anal sis o is acto s and
o tcomes st act stet necol ep od iol
c ead thie an n shle Tan imanpana a ilapai n en
et al ia nostic and T eatment i fic lties o eloneph itis in e nanc in
eso ce imited ettin s m T op ed
ill he field cInti e endel c te p eloneph itis in
p e nanc stet necol
in a e e illa imited clinical tilit o lood and ine
cultures in the treatment of acute pyelonephritis during pregnancy. Am J Obstet
necol
eidman o iano lit i e man ashiach a ai ole
of renal ultrasonography in the management of pyelonephritis in pregnant
omen st act e inatol
a e C alos T eatments o s mptomatic ina t act in ections d in
p e nanc Coch ane ata ase o stematic e ie s C
C ide Cle es ee h is e o s C nti acte ial
edication Use in e nanc and is o i th e ects ational i th
e ects e ention t d ch ediat dolesc ed
l onamides it o antoin and is o i th e ects Committee pinion
o me ican Colle e o stet icians and necolo ists stet necol
chnee e e C ee lin s iddleton C o the C Inte entions o

p e entin ec ent ina t act in ection d in p e nanc e ie Coch ane
ata ase o stematic e ie s C
in a mne eslic a C Ch n ail c an e ice o the
p e ention o as mptomatic acte i ia in p e nanc a andomi ed cont olled
pilot st d The o nal o olo ct
• ACKNOWLEDGEMENT •
The UTI Tas o ce is ate l o the ndin s ppo t i en

the hilippine ociet o ic o iolo and In ectio s isease o
the de elopment and p intin o this Clinical actice idelines

IO L O G
RO B YA
IC N
M
D
R
FO
Philippine Society for Microbiology and Infectious Diseases

IN
FE
S O CIE TY
C TIO U S DIS
No. 116 9th Avenue, Cubao

IN E
Quezon City 1109 Philippines

PP
EA
LI
I ES
PH
---1 --
9 70 AD-
Philippine Clinical Practice Guidelines on the Diagnosis and
Management of Urinary Tract Infections in Adults
2015 Update: Part 2
Asymptomatic Bacteriuria in Adults, Recurrent Urinary Tract

Infection, and Complicated Urinary Tract Infection
Task Force Members
Organizations
Philippine Society for Microbiology and Infectious Diseases
Philippine Obstetrics and Gynaecology Society
Philippine Society of Nephrology
Philippine Urological Association
Philippine Academy of Family Physicians
Chair: Mediadora C. Saniel, MD

Co-chair: Marissa M. Alejandria, MD
Complicated Urinary Tract Infection Cluster

Arthur Dessi E. Roman, MD (Head) Jill R. Itable, MD
Allan Raymond S. Tenorio, MD (Head) Marie Carmela M. Lapitan, MD
Rufino T. Agudera, MD Maria Nicollete M. Mariano, MD
Anne Margaret J. Ang, MD Katha W. Ngo-Sanchez, MD
Regina P. Berba, MD
Recurrent UTI Cluster

Marissa M. Alejandria, MD Rommel Bataclan, MD
Coralie Therese Dimacali, MD Tenille Tan, MD
Leilanie Apostol-Nicodemus, MD Mark Brian Tan, MD
Asymptomatic Bacteriuria in Adults Cluster

Ricardo M. Manalastas Jr., MD (Head) Jill R. Itable, MD
Louella P. Aquino, MD Alfredo M. Lopez, Jr, MD
Shahreza L. Baquiran, MD Helen V. Madamba, MD
Sybil Lizzane R. Bravo, MD Josefa Dawn V. Martin, MD
Jennifer T. Co, MD Erwin R. De Mesa, MD
Maria Meden P. Cortero, MD Sharon Faith B. Pagunsan, MD
Lorina Q. Esteban, MD Oliver S. Sanchez, MD
Analyn F. Fallarme, MD Katha W. Ngo-Sanchez, MD
May Gabaldon, MD
Research Associates:
Richelle G. Duque, MD and Grace Kathleen T. Serrano, MD
Philippine Clinical Practice Guidelines on UTI 2015 Update: Part 2
1
TABLE OF CONTENTS
3 Introduction
3 Methodology
6 Asymptomatic Bacteriuria in Adults
17 Recurrent Urinary Tract Infection in Women
46 Complicated Urinary Tract Infections: General
Considerations
70 Specific Issues of Concern in Complicated UTI
70 UTI in Diabetic Patients
74 Catheter-Associated Urinary Tract Infection
99 Renal Abscess
108 UTI in Renal Transplant Patients
115 Perioperative Antibiotic Prophylaxis for Patients Who
will Undergo Urologic Procedures
124 Urinary Candidiasis
2
Introduction
INTRODUCTION
Urinary tract infections (UTI) are among the leading indications for seeking
healthcare and using antimicrobials in the community and hospital settings. The
Philippine Clinical Practice Guidelines on the Diagnosis and Management of Urinary
Tract Infections in Adults were first published in 1998 and revised in 2004 to provide
primary care physicians and specialists with evidence-based recommendations on the
care of patients with UTI. The current guidelines further update the recommendations
following an extensive review of more recent literature. For the first time the GRADE
(Grading of Recommendations Assessment, Development, and Evaluation) system
was used to develop guidelines in infectious diseases in the country. The outputs are
consensus recommendations of a panel of clinicians convened by the Philippine
Society for Microbiology and Infectious Diseases (PSMID) in collaboration with the
Philippine Obstetric and Gynecological Society (POGS), Philippine Society of
Nephrology (PSN), Philippine Academy of Family Physicians (PAFP), and Philippine
Urological Association (PUA).
The focus of the guidelines is on diagnosis, treatment, and prevention of UTI in
adults and consists of two parts:
Part One – Acute Uncomplicated UTI and UTI in Pregnancy
Part Two – Asymptomatic Bacteriuria, Recurrent UTI
and Complicated UTI
In formulating optimal approaches to the care of both outpatients and inpatients
with UTI, the panel considered several issues related to changing prevalence and
resistance patterns of uropathogens, availability and practicability of diagnostic tests,
and cost-effectiveness and ecological adverse effects (collateral damage) of treatment.
The guidelines are not intended to supersede a healthcare provider’s sound
clinical judgment. Variations in clinical presentation, presence of comorbidities, or
availability of resources may require adaptation of the recommendations to specific
settings.
METHODOLOGY
The PSMID, in collaboration with POGS, PSN, PAFP, and PUA, convened a
task force of clinicians representing different expertise including infectious diseases,
nephrology, family medicine, obstetrics and gynecology, urology, and internal medicine.
The members of this task force were divided into four clusters, each headed by a senior
specialist, and served as the technical working group for formulating the guidelines. The
areas covered were: Cluster A – uncomplicated UTI (acute cystitis and pyelonephritis),
Cluster B – UTI in pregnancy and asymptomatic bacteriuria, Cluster C – complicated
UTI, and Cluster D – recurrent UTI.
Each cluster conducted a review and analysis of the relevant English literature
published since 2004 and, for some topics, even earlier studies. The quality of the
evidence was evaluated using the GRADE system as indicated in Table 1. The cluster
then drafted guideline recommendations and graded them as STRONG or WEAK
depending on the quality of the evidence, balance of potential benefits and harm, and
translation into practice in specific settings and patient groups. Thus, high-quality
evidence did not necessarily constitute strong recommendations; conversely, strong
recommendations could arise from low-quality evidence if the benefits outweigh the
undesirable consequences.
3
Introduction
Table 1. GRADE system

Category Definition
Strength of Recommendation
Strong Desirable effects (benefits) clearly outweigh the undesirable effects
(risks)
Conditional Desirable effects probably outweigh the undesirable effects but the
recommendation is applicable only to a specific group, population, or
setting; or the benefits may not warrant the cost or resource
requirements in all settings
Weak Desirable and undesirable effects closely balanced;or uncertain, new
evidence may change the balance of risk to benefit
No Further research is required before any recommendation can be

recommendation made
Quality of Evidence
High Consistent evidence from well-performed RCTs or strong evidence
from unbiased observational studies; further research is very unlikely
to change confidence in the estimate of the effect
Moderate Evidence from RCTs with important limitations or moderately strong

evidence from unbiased observational studies; further research is
likely to have an important impact on confidence in the estimate of
the effect
Low Evidence for ≥ one critical outcome from observational studies, from
RCTs with serious flaws or from indirect evidence; further research
is very likely to have an important impact in the estimate of effect and
is likely to change the estimate
Very Low Evidence for ≥ one critical outcome from unsystematic clinical
observations or very indirect evidence; any evidence of effect is very
uncertain
In addition to quality of evidence, the following domains were considered in

grading the strength of the recommendations:
1. Balance of benefits versus harms and burdens
2. Values and preferences: Is the recommendation likely to be widely accepted or
Is there significant variability or uncertainty in values and preferences that the
recommendation is unlikely to be accepted?
3. Resource implications: financial costs/implications, infrastructure, equipment,
human resources/expertise, cost-effectiveness
4. Feasibility: Is the recommendation achievable in the setting where the greatest
impact is expected?
A series of face-to-face meetings of the task force with representatives from all
four clusters was held to discuss each cluster’s draft outputs. The task force members
4
Introduction
developed a consensus in grading the quality of the evidence and strength of the
recommendations using the GRADE technique. Throughout the development process,
expert advice on methodological issues was provided by a task force member proficient
in the GRADE system. GRADE tables summarizing the quality of the evidence retrieved
were generated for each guideline question.
Segments of the guidelines were presented in various fora including annual
conventions of specialty societies such as POGS, PSN, and PSMID to elicit feedback.
The guidelines were finalized after a few more meetings and e-mail correspondence
among the task force members and cluster heads. At regular intervals, the task force
leaders will determine the need for revisions to the guidelines. Implementation
strategies will also be periodically reviewed.
References:
1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE:
an emerging consensus on rating quality of evidence and strength of recommendations.
BMJ 2008; 336:924–6.
2. Guyatt GH, Oxman AD, Kunz R, Falck-Ytter Y, Vist GE, Liberati A, et al. Going from
evidence to recommendations. BMJ 2008; 336:1049–51.
5
Asymptomatic bacteriuria
ASYMPTOMATIC BACTERIURIA IN ADULTS
Summary of recommendations
1. When is asymptomatic bacteriuria diagnosed?
1.1. All diagnosis of asymptomatic bacteriuria (ASB) should be based on
results of urine culture specimens that are collected aseptically and
with no evidence of contamination.
1.2. For asymptomatic women, bacteriuria is defined as two consecutive
voided urine specimens with isolation of the same bacterial strain in
quantitative counts ≥ 100,000 cfu/mL.
1.3. In men, a single, clean-catch voided urine specimen with one bacterial
species isolated in a quantitative count ≥ 100,000 cfu/mL identifies
bacteriuria.
1.4. In both men and women, a single catheterized urine specimen with
one bacterial species isolated in a quantitative count ≥ 100 cfu/mL
identifies bacteriuria.
2. What are the indications for screening and treatment of asymptomatic
bacteriuria?
2.1. Screening and treatment is recommended in the following to prevent
bacteremia and sepsis:
Patients who will undergo genitourinary manipulation or
instrumentation
Recommendations vary per selected procedure
All pregnant women
Strong Recommendation, High quality of evidence
2.2. The choice of antibiotic depends on culture results. A seven-day
regimen is recommended.
Strong Recommendation, Low quality of evidence
2.3. For specific antibiotic recommendations for ASB in pregnancy, see Table 2.
Table 2. Antibiotics that can be used for ASB in pregnancy

Antibiotics Recommended dose FDA Risk
and duration Category
Cefuroxime axetil 500 mg BID for 7 days B
Fosfomycin trometamol 3 g single dose B
Nitrofurantoin* 100 mg QID for 7 days; B
macrocrystal 100 mg BID for 7 days for
monohydrate macrocrystal
formulation
(not available locally)
Trimethoprim- 160/800 mg BID for 7 days C (avoid in
sulfamethoxazole 1st and 3rd
trimester)
6
* May cause hemolytic anemia, anophthalmia, hypoplastic left heart syndrome, ASD,
cleft lip and palate. May be given on the second trimester of pregnancy until 32 weeks
AOG. Use in the first trimester of pregnancy is appropriate when no other suitable
alternative antibiotics are available.
3. Who should NOT be screened and treated for asymptomatic bacteriuria?

3.1. Routine screening and treatment for asymptomatic bacteriuria is not
recommended for healthy adults.
3.2. Likewise, periodic screening and treatment for asymptomatic
bacteriuria is not recommended in the following:
Patients with diabetes mellitus
Elderly patients
Patients with indwelling catheters
Weak Recommendation, Moderate quality of evidence
Solid organ transplant patients
People living with human immunodeficiency virus (HIV)
Spinal cord injury patients
Weak Recommendation, Very low quality of evidence
Patients with urologic abnormalities
Weak recommendation, Very Low quality of evidence
4. What is the optimal screening test for asymptomatic bacteriuria?

4.1. Screening by urine culture is recommended.
4.2. In the absence of facilities for urine culture, significant pyuria (>10
wbc/hpf) or a positive gram stain of unspun urine (>2
microorganisms/oif) in two consecutive midstream urine samples can
be used to screen for asymptomatic bacteriuria.
4.3. Urine culture and sensitivity testing are not necessary when urinalysis
is negative for pyuria or urine gram stain is negative for organisms.
Strong Recommendation, Moderate quality of evidence
4.4. Pyuria accompanying asymptomatic bacteriuria is not an indication for
antimicrobial treatment among patients for whom screening and
treatment is not recommended.
7
DISCUSSION
1. When is asymptomatic bacteriuria diagnosed?
1.1. All diagnosis of asymptomatic bacteriuria (ASB) should be based on

results of urine culture specimens that are collected aseptically and
with no evidence of contamination.
1.2. For asymptomatic women, bacteriuria is defined as two consecutive
voided urine specimens with isolation of the same bacterial strain in
quantitative counts ≥ 100,000 cfu/mL.
Summary of Evidence
The definition of asymptomatic bacteriuria as bacterial counts more than or
equal to 105 cfu/mL, in two consecutive urine specimens was based on studies
done in the 1940s to 1950s, where such bacterial counts in clean, voided
specimens were confirmed by a catheterized sample in more than 95% of
cases.1 According to Hooton et al, 2000, transient bacteriuria is common in
healthy young women, and occurs in around 5% to 6% but rarely persists. 2 As
such, if more than one specimen is used to identify bacteriuria, the prevalence
will be lower.1
1.3. In men, a single, clean-catch voided urine specimen with one bacterial
species isolated in a quantitative count ≥ 100,000 cfu/mL identifies
bacteriuria.
Summary of Evidence
In asymptomatic, ambulatory men, Enterobacteriaceae counts of greater
than or equal to 105 cfu/ml in a single, voided, urine specimen was reproducible
in repeat cultures done within one week from initial culture in 98% of cases. 1,3
1.4. In both men and women, a single catheterized urine specimen with
one bacterial species isolated in a quantitative count ≥ 100 cfu/mL
identifies bacteriuria.
Summary of Evidence
For both men and women whose specimens are drawn via urethral
catheterization, bacteriuria is consistent with quantitative counts of greater than
or equal to 100 cfu/mL.1,4
2. What are the indications for screening and treatment of asymptomatic

bacteriuria?
2.1. Screening and treatment is recommended in the following to prevent

bacteremia and sepsis:
Patients who will undergo genitourinary manipulation or
instrumentation
8
Recommendations vary per selected procedure

All pregnant women
2.2. The choice of antibiotic depends on culture results. A seven-day

regimen is recommended.
2.3. For specific antibiotic recommendations for ASB in pregnancy, see Table 2.
Table 2. Antibiotics that can be used for ASB in pregnancy

Antibiotics Recommended dose FDA Risk
and duration Category
Cefuroxime axetil 500 mg BID for 7 days B
Fosfomycin trometamol 3 g single dose B
Nitrofurantoin* 100 mg QID for 7 days; B
macrocrystal 100 mg BID for 7 days for
monohydrate macrocrystal
formulation
(not available locally)
Trimethoprim- 160/800 mg BID for 7 days C (avoid in
sulfamethoxazole 1st and 3rd
trimester)
* May cause hemolytic anemia, anophthalmia, hypoplastic left heart syndrome, ASD,
cleft lip and palate. May be given on the second trimester of pregnancy until 32 weeks
AOG. Use in the first trimester of pregnancy is appropriate when no other suitable
alternative antibiotics are available.
Summary of Evidence
Genitourinary procedures
Genitourinary surgery with trauma and bleeding of the mucosa allows organisms
in the urinary tract to invade the systemic circulation. Antimicrobial treatment of
asymptomatic bacteriuria before genitourinary manipulation or instrumentation can
prevent bacteremia and sepsis.5-7 In patients with bacteriuria undergoing a traumatic
urologic procedure, 25% to 80% will have bacteremia if no treatment is given. 5
For patients who will undergo elective urologic procedures with asymptomatic
bacteriuria on screening, they should be treated accordingly based on the culture result.
For emergency cases, antibiotic prophylaxis is recommended with cultures ideally
obtained prior to antibiotic administration.
For a detailed discussion on antibiotic prophylaxis prior to selected urologic
procedures, refer to section on Complicated UTI.
Pregnant women
See the section on UTI in Pregnancy for discussion.
9
3. Who should NOT be screened and treated for asymptomatic bacteriuria?

3.1. Routine screening and treatment for asymptomatic bacteriuria is not
recommended for healthy adults.
3.2. Likewise, periodic screening and treatment for asymptomatic
bacteriuria is not recommended in the following:
Patients with diabetes mellitus
Elderly patients
Weak Recommendation, Moderate quality of evidence
People living with human immunodeficiency virus (HIV)

Weak Recommendation, Very low quality of evidence
Patients with urologic abnormalities
Weak recommendation, Very Low quality of evidence
Summary of Evidence
Healthy adults
Cai et al (2012) studied 673 young (age 18 to 40 years), asymptomatic, sexually
active women with at least one symptomatic urinary tract infection (UTI) treated within
the past 12 months prior to the current bacteriuric episode, with a urine culture showing
at least 105 cfu/mL of uropathogens.8 Screening and antibiotic treatment of
asymptomatic bacteriuria in this population failed to show any benefit.
Diabetes Mellitus patients

There are no population-based surveys of ASB among Filipino diabetics. The
prevalence of asymptomatic bacteriuria among women undergoing treatment for
diabetes is 7% to 13%, generally threefold higher than in non-diabetic women. The
prevalence of asymptomatic bacteriuria is not increased compared to non-diabetic men
(ranging from 0.7 to 11.1%). Most studies have shown that the type or duration of
diabetes, or the adequacy of diabetic control do not influence the prevalence of
asymptomatic bacteriuria.9 However, a survey among diabetic aboriginal women in
Canada found that the duration of the diabetes and presence of long-term complications
including retinopathy, nephropathy and neuropathy were associated with asymptomatic
bacteriuria.10 This increased prevalence of asymptomatic bacteriuria in diabetic women
may be largely attributable to autonomic neuropathy leading to impaired bladder
voiding.11 A case-control study of 228 women with diabetes and 146 women without
diabetes showed that impaired metabolic control of diabetes, as revealed by higher
glycated hemoglobin levels, significantly increased the risk for developing
asymptomatic bacteriuria (p<0.05).12
10
In the randomized controlled trial (RCT) by Harding et al (2002), there was greater
antimicrobial exposure and higher frequency of adverse drug effects among those
treated for asymptomatic bacteriuria.13 Women in the treatment group also had
significantly more episodes of asymptomatic bacteriuria following therapy.
No added benefit for screening and treatment of asymptomatic bacteriuria in
diabetic women was demonstrated. On intention-to-treat analysis after a mean follow-
up of 27 months, the proportion of patients having more than one episode of
symptomatic UTI did not differ between those who had antimicrobial therapy and those
on placebo (41% vs. 40%). There was also no difference in terms of the time to a first
symptomatic UTI episode. Likewise, no significant difference in the occurrence of
pyelonephritis, cystitis, or all episodes of UTI and hospitalizations due to UTI or to other
causes was observed. They noted that glycosuria and neuropathy might be associated
with symptomatic infection but not asymptomatic bacteriuria. 13
Long-term prospective studies of the natural history of diabetic women also
showed that accelerated progression to hypertension, renal failure or other long-term
complications was similar for those with and without asymptomatic bacteriuria. 14,15
Elderly patients
There are no population-based studies on ASB among elderly Filipinos. Various
surveys of community populations in developed countries show that the prevalence of
asymptomatic bacteriuria increases with age irrespective of sexual activity. In women
50 to 60 years of age, the prevalence is 6% to 7%; and 8-10% at age 70 to 80 years.16
In non-institutionalized elderly men, the prevalence is 12%. 17 It is highest among
institutionalized elderly women (25% to 57%) and men (15% to 37%). The prevalence
in young to middle-aged adults is less than 5% in women and 1.5% in men. 18
A cross-sectional study by Rodhe et al in 2006 showed that bacteriuria was
common among the non-institutionalized elderly aged 80 and over, especially among
the women, but still not as common as among the elderly in institutional settings. 19
Lin et al (2006) did a prevalence study on ASB in 64 institutionalized elderly
Chinese.20 Overall prevalence of asymptomatic bacteriuria in this study was 57.8%.
Escherichia coli was the most commonly isolated organism. No association was found
between ASB and factors such as age, sex, functional status, indwelling catheter,
previous history of UTI, or nutritional status of residents.
No recent study showed significant benefit in the treatment of ASB in the elderly
population. A cohort study of ambulatory elderly women showed that ASB was not
independently associated with mortality. 21 Controlled clinical trials on treatment versus
no treatment of ambulatory elderly women found that treatment of ASB did not
significantly reduce mortality and symptomatic episodes of UTI. 21,22 RCTs comparing
treatment versus no treatment on elderly institutionalized men and women showed no
benefits with treatment.18,21,23,24 An association with asymptomatic bacteriuria and
increased 5-year mortality was reported in elderly women in a Finnish study; however,
subsequent reports with 5- and 9-year follow-up have not reported an association of
asymptomatic bacteriuria and survival for either men or women. 23,25
Two RCTs among institutionalized elderly women showed increased rates of
adverse reactions from antimicrobial therapy, with one showing an increased frequency
of re-infection with resistant organisms.18,24
11

See the section on SPECIFIC ISSUES OF CONCERN IN COMPLICATED UTI:
CATHETER-ASSOCIATED UTI.

No new evidence was found that would support a change in the recommendations
from the previous guideline.
Patients with spinal cord injury have a high prevalence of bacteriuria ranging from
20% to 98%.22 Prospective cohort studies however do not report progression to renal
failure with bacteriuria if low bladder pressure is maintained either by intermittent
catheterization, condom drainage or sphincterotomy, as necessary. 26 A small placebo-
controlled trial reported no decrease in symptomatic infection with treatment of
bacteriuria.27

Studies on screening and treatment of asymptomatic bacteriuria among post-renal
transplant patients are limited.
In a retrospective analysis of 189 renal transplant patients who were systematically
screened for ASB, various outcomes were compared between those who developed
asymptomatic bacteriuria and those who did not. 28 Ninety-six patients developed
asymptomatic bacteriuria, and all of them were treated accordingly. Having more than
one episode of bacteriuria was associated with pyelonephritis. Having more than five
episodes of bacteriuria was associated with organ rejection. However, despite
treatment, the incidence of pyelonephritis was higher in patients screened and treated
for asymptomatic bacteriuria compared to those who did not develop bacteriuria (7.6 vs
1.07 episodes per 100 patient-years). There was also no difference in renal function
prognosis measured in terms of creatinine, creatinine clearance and proteinuria in both
groups when the number of asymptomatic bacteriuria episodes was taken into account.
The authors concluded that screening and treatment of those with asymptomatic
bacteriuria may be the reason for the similarity in terms of renal function prognosis to
those who did not develop asymptomatic bacteriuria. It is important to note, however,
that the authors were not able to compare outcomes between patients that developed
bacteriuria who received treatment and those who did not receive treatment. Thus, the
influence of screening and treatment of asymptomatic bacteriuria among post-renal
transplant patients was not directly demonstrated in this study.
Similar findings were also seen in a review on 86 patients who received renal
allografts, wherein one-fifth of the patients developed urinary infections by 6 months
after transplantation.29 There were no significant differences in the transplant function
and in the patient and graft survival between the infected group and that of the sterile
group.
Two retrospective studies evaluated the outcome of treating vs not treating
asymptomatic bacteriuria in post-kidney transplant patients. Amari et al did a
retrospective analysis on the outcome of 334 asymptomatic bacteriuria that occurred in
77 renal transplant recipients later than 1 month post-transplantation.30 They observed
no differences when comparing progression toward symptomatic UTI between all
treated and untreated episodes (0/101 versus 4/233; p=0.32). Spontaneous clearance
of the initial pathogen in all untreated episodes was as frequent as microbiological cure
12
of treated episodes (138/233 versus 55/101; p=0.47). In a retrospective cohort study by

Green et al, no benefit was observed from the antibiotic treatment of asymptomatic
bacteriuria in the short- and long-term follow-up.31
Several good quality studies have shown the advantage of antibiotic prophylaxis
in the prevention of bacteriuria and bacteremia in renal transplant recipients. Antibiotic
prophylaxis during the post-transplant period undermines the potential benefit of
systematic screening for asymptomatic bacteriuria in this subset of patients. For a
detailed discussion on antibiotic prophylaxis after renal transplantation, refer to the UTI
in Renal Transplant Patients section under Complicated UTI.
For solid organ transplant patients other than renal transplant recipients, there is
no evidence to recommend screening and treatment of asymptomatic bacteriuria.
According to the American Society of Transplantation, there is no consensus whether
asymptomatic bacteriuria should be treated in the transplant patient. 32 Even with the
use of prophylactic antibiotics, infection-related fatality rates are not reduced.
People living with HIV

The prevalence of bacteriuria in 222 female prostitutes in Kenya was 23%. The
proportions of those who were HIV-positive and HIV-negative were similar, and
bacteriuria did not vary with the CD4+ count.33 In a cross-sectional study comparing
men with acquired immune deficiency syndrome (group A), men without HIV (group B)
and men with asymptomatic HIV infection (group C), bacteriuria was significantly more
frequent in group A (20 cases, 13.3%) than in groups B (3 cases, 1%-8%; p=0.00007)
and C (3 cases, 3.2%; p=0.009). Ten cases of bacteriuria in group A (6.6%) were
symptomatic while no case of symptomatic UTI was seen in groups B (p=0.0004) and
C (p=0.008).34 Morbidity was associated with symptomatic UTI but negative clinical
outcomes due to asymptomatic bacteriuria in HIV patients were not reported.
Urologic abnormalities
Among patients with genitourinary abnormalities, the incidence of ASB depends
on the primary renal disease.7 Asymptomatic bacteriuria is not present more frequently
in autosomal dominant polycystic kidney disease patients with normal kidney function
and no diabetes, than in healthy people.35 In a comparative study of prevalence of ASB
in a Thai population, there was a higher overall prevalence of ASB in those with
glomerulonephropathies when compared to the controls. 36 There were no reports
showing increased risk of symptomatic infection or further complications as a
consequence of ASB among patients with urologic abnormalities.
Comments: The criteria used in deciding whether to screen or not for any disease
condition depends on the burden of the disease condition, performance characteristics
of the screening test, the effectiveness of interventions for treatment or prevention of
transmission once infection has been detected, and the cost effectiveness of the
screening test and the treatment or preventive intervention.
4. What is the optimal screening test for asymptomatic bacteriuria?
4.1. Screening by urine culture is recommended.

13
Summary of Evidence
Urine culture remains the gold standard for diagnosing asymptomatic
bacteriuria, particularly in pregnant women, as no other tests have a high enough
sensitivity and negative predictive value to replace urine cultures for screening. 37
4.2. In the absence of facilities for urine culture, significant pyuria (>10
wbc/hpf) or a positive gram stain of unspun urine (>2
microorganisms/oif) in two consecutive midstream urine samples can
be used to screen for asymptomatic bacteriuria.
4.3. Urine culture and sensitivity testing are not necessary when urinalysis
is negative for pyuria or urine gram stain is negative for organisms.
Strong Recommendation, Moderate quality of evidence
Summary of evidence
Pyuria has a good predictive value in patient populations where the
prevalence of asymptomatic bacteriuria is at least 10%. With pyuria of greater
than 10 wbc/hpf, the likelihood ratio for a significant urine culture result among
ambulatory elderly men was 417; for 2 to 10 wbc/hpf, the likelihood ratio was 2;
for 0 to 1 wbc/hpf, the likelihood ratio was 0.03. 38
4.4. Pyuria accompanying asymptomatic bacteriuria is not an indication for

antimicrobial treatment among patients for whom screening and
treatment is not recommended.
Summary of Evidence
In the absence of symptoms or signs referable to UTI, bacteriuria, although
microbiologically significant, is not clinically significant. Pyuria is evidence of
inflammation in the genitourinary tract and is common in persons with
asymptomatic bacteriuria such as in young women. 2 diabetic women, elderly
institutionalized patients, hemodialysis patients, bacteriuric patients with short-
term catheters, and in individuals with long-term indwelling catheters in place – all
of whom screening and treatment for asymptomatic bacteriuria is not
recommended. Pyuria also accompanies other inflammatory conditions of the
genitourinary tract in patients with negative urine culture results. The dilemma of
the positive culture with pyuria in an asymptomatic patient can be avoided if
urinalysis and urine cultures are not done on asymptomatic patients for whom
screening and treatment is not recommended.2,13,18,23
References:
1. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases
Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria
in Adults. Clin Infect Dis 2005; 40:643-54.
2. Hooton TM, Scholees D, Stapleton AE, et al. A prospective study of asymptomatic bacteriuria
in sexually active young women. N Engl J Med 2000;23:744-9.
14
3. Gleckman R, Esposito A, Crowley M, Nastios GA. Reliability of a single urine culture in

establishing diagnosis of asymptomatic bacteriuria in adult males. J Clin Microbiol
1979;9:596-7.
4. Saint SJ, Chenoweth CE. Biofilms and catheter-associated urinary tract infections. Infect Dis
Clin North Am 2003;17:411-32.
5. Olson ES, Cookson BD. Do antimicrobials have a role in preventing septicaemia following
instrumentation of the urinary tract? J Hosp Infect 2000;45:85-97.
6. Grabe M. Perioperative antibiotic prophylaxis in urology. Curr Opin Urol 2001;11:81-5.
7. Zhanel GG, Harding GKM, Guay DRP. Asymptomatic bacteriuria: which patients should be
treated? Arch Intern Med 1990;150:1389-97.
8. Cai T, Mazzoli S, Mondaini N, Meacci F, Nesi G, D’Elia C, et al. The Role of Asymptomatic
Bacteriuria in Young Women with Recurrent Urinary Tract Infections: to Treat or Not to
Treat? Clin Infect Dis 2012;55:771-7.
9. Zhanel GG, Harding GK, Nicolle LE. Asymptomatic bacteriuria in patients with diabetes
mellitus. Rev Infect Dis 1991;13:150-4.
10. Zhanel GG, Harding GK, Nicolle LE. Prevalence of asymptomatic bacteriuria and associated
host factors in women with diabetes mellitus. Clin Infect Dis 1995;21:316-22.
11. Patterson JE, Andriole VT. Bacterial urinary tract infections in diabetes. Infect Dis Clin North
Am 1997;11:735-50.
12. Bonadio M, Boldrini E, Forotti G, et al. Asymptomatic bacteriuria in women with diabetes:
influence of metabolic control. Clin Infect Dis 2004;38:e41-5.
13. Harding GKM, Zhanel GG, Nicolle LE, Cheang M. Antimicrobial treatment in diabetic women
with asymptomatic bacteruria. N Engl J Med 2002;347:1576-1583.
14. Geerlings SE, Stolk RP, Camps MJ, Netten PM, Collet JT, Schneeberger PM, Hoepelman
AI. Consequences of asymptomatic bacteriuria in women with diabetes mellitus. Arch Intern
Med 2001 Jun 11;161(11):1421-7.
15. Semetkowska-Jurkiewicz E, Horoszek-Maziarz S, Galiński J, Manitius A, Krupa-
Wojciechowska B The clinical course of untreated asymptomatic bacteriuria in diabetic
patients--14-year follow-up. Mater Med Pol 1995 Jul-Sep;27(3):91-5.
16. Kunin CM, McCormack RC. An epidemiologic study of bacteriuria and blood pressure among
nuns and working women. N Engl J Med 1968 Mar 21;278(12):635-42.
17. Mims AD, Norman DC, Yamamura RH, Yoshikawa TT. Clinically inapparent (asymptomatic)
bacteriuria in ambulatory elderly men: epidemiological, clinical, and microbiological findings.
J Am Geriatr Soc 1990 Nov;38(11):1209-14.
18. Nicolle LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am 1997;11:647-
62.
19. Rodhe N, Mölstad S, Englund L, Svärdsudd K. Asymptomatic bacteriuria in a population of
elderly residents living in a community setting: prevalence, characteristics and associated
factors. Fam Pract 2006;23:303–7.
20. Lin Y, Chen L, Lin M, Hwang S. Asymptomatic Bacteriuria among Institutionalized Elderly. J
Chin Med Assoc 2006;69:213-217.
21. Abrutyn E, Mossey J, Berlin JA, et al. Does asymptomatic bacteriuria predict mortality and
does antimicrobial treatment reduce mortality in elderly ambulatory women? Ann Intern Med
1994;120:827–33.
22. Boscia JA, Kobasa WD, Knight RA, Abrutyn E, Levison ME, Kaye D. Therapy vs. no therapy
for bacteriuria in elderly, ambulatory, nonhospitalized women. JAMA 1987; 257:1067–71.
23. Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infect Clin North
Am 2003; 17: 367-94.
24. Ouslander JG, Schapira M, Schnelle JF, et al. Does eradicating bacteriuria affect the severity
of chronic urinary incontinence in nursing home residents? Ann Intern Med 1995; 122:749–
54.
25. Sourander LB, Kasanen A. A 5-year follow-up of bacteriuria in the aged. Gerontol Clin
(Basel) 1972;14(5):274–281.
26. Sotolongo JR Jr, Koleilat N. Significance of asymptomatic bacteriuria in spinal cord injury
patients on condom catheter. J Urol 1990;143(5):979-980.
15
27. Mohler JL, Cowen DL, Flanigan RC. Suppression and treatment of urinary tract infection in
patients with an intermittently catheterized neurogenic bladder. J Urol 1987;138:336–40.
28. Fiorante S, Lopez-Medrano F, Lizasoain M, Lalueza A, Juan RS, Andres A, et al. Systematic
screening and treatment of asymptomatic bacteriuria in renal transplant recipients. Kidney
International 2010;78:774-781.
29. Griffin PJA, Salaman JR. Urinary tract infections after renal transplantation: Do they matter?
BMJ 1979;1:710-1.
30. Amari EBE, Hadaya K, Buhler L, Berey T, Rohner P, Martin P, Mentha G, van Delden C.
Outcome of treated and untreated asymptomatic bacteriuria in renal transplant recipients.
Nephrol Dial Transplant 2011;26:4109-4114.
31. Green H, Rahamimov R, Goldberg E, Leibovici L, Gafter U, Bishara J, et al. Consequences
of treated versus untreated asymptomatic bacteriuria in the first year following kidney
transplantation: retrospective observational study. Eur J Clin Microbiol Infect Dis
2013;32:127-31.
32. Rice JC, Safdarb N, AST Infectious Diseases Community of Practice. Urinary Tract
Infections in Solid Organ Transplant Recipients. Am J Transplant 2009;9(Suppl 4): S267–
72.
33. Ojoo J, Paul J, Batchelor B, Amir M, Kimari J, Mwachari C, Bwayo J, Plummer F, Gachihi1
G, Waiyaki P, Gilks C. Bacteriuria in a cohort of predominantly HIV-1 seropositive female
commercial sex workers in Nairobi, Kenya. J Infect 1996;33:33–7.
34. De Pinho AMF, Lopes GS, Ramos-Filho CF, Santos OD, De Oliveira MPB, Halpem M, et al.
Urinary Tract Infection in Men with AIDS. Genitourin Med 1994;70:30-4.
35. Pietrzak-Nowacka M, Giedrys-Kalemba S, Safranow K, Szymaniak L, Nowosiad M,
Korzonek M, Sulikowski T, Ciechanowski K. (Is autosomal dominant polycystic kidney
disease associated with asymptomatic bacteriuria?) Pol Merkur Lekarski 2010 Sep;29:173-
6.
36. Phanichphant S, Boonpucknavig V. Asymptomatic bacteriuria in health and
glomerulonephropathies. Nephron 1986;44:121-4.
37. Lin K, Fajardo K; U.S. Preventive Services Task Force. Screening for asymptomatic
bacteriuria in adults: evidence for the US Preventive Services Task Force reaffirmation
recommendation statement. Ann Intern Med. 2008;149:W20-4.
38. Norman DC, Yamamura R. Yoshikawa TT. Pyuria: Its predictive value of asymptomatic
bacteriuria in ambulatory elderly men. J Urol 1996;135:520-2.
16
Recurrent UTI in women
RECURRENT URINARY TRACT INFECTION IN WOMEN
1. How is recurrent urinary tract infection (rUTI) diagnosed?
1.1. Recurrent UTI is diagnosed when a healthy non-pregnant woman with
no known urinary tract abnormalities has 3 or more episodes of acute
uncomplicated cystitis documented by urine culture during a 12-month
period OR 2 or more episodes in a 6- month period.1-3
1.2. Recurrent UTI may either be a relapse or a reinfection. Relapse occurs
when the initial organism persists within the urinary tract and re-
emerges despite adequate treatment usually occurring 1-2 weeks after
stopping treatment. Reinfection, on the other hand, occurs when
recurrent UTI is caused by a different bacterial isolate, or by the
previously isolated bacteria after a negative intervening culture or an
adequate period (≥ 2 weeks) between infections.4,5
2. Among those with recurrent UTI, who would benefit from further diagnostic
evaluation?
2.1. Routine screening for urologic abnormalities is not recommended for
the general patient population.
Strong recommendation, low quality of evidence
2.2. Screening for urologic abnormalities is recommended in the following
situations:
No response to appropriate antimicrobial therapy or rapid relapse
after such therapy
Gross hematuria during a UTI episode or persistent microscopic
hematuria
Obstructive symptoms
Clinical impression of persistent infection
Infection with urea-splitting bacteria (Proteus, Morganella,
Providencia)
History of pyelonephritis
History of or symptoms suggestive of urolithiasis
History of childhood UTI
Elevated serum creatinine
2.3. Patients with the above factors may benefit from further diagnostic
evaluation as these risk factors have been identified to be associated
with a higher incidence of urologic abnormalities.
2.4. All women with recurrent UTI should undergo a complete history and
physical examination to evaluate urogenital anatomy and
estrogenization of vaginal tissues and to detect prolapse. Post-void
residual urine should be measured.
3. What diagnostic work-ups are indicated in women with recurrent UTI?
3.1. Radiologic or imaging studies and cystoscopy are not routinely
indicated in patients with recurrent UTI.
Weak recommendation, low quality of evidence
3.2. Renal ultrasound or CT scan/stonogram may be done to screen for
urologic abnormalities
17
3.3. Patients with anatomical abnormalities should be referred to a

specialist (nephrologist or urologist) for further evaluation.
4. When is prophylaxis for recurrent UTI indicated?
4.1. Prophylaxis is recommended in women whose frequency of recurrence
is not acceptable to the patient in terms of level of discomfort or
interference with activities of daily living. Prophylaxis may be withheld
according to patient preference if the frequency of recurrence is
tolerable to the patient.
Strong recommendation, low quality of eviden
4.2. The following factors should guide the physician in determining the
patient’s risk-benefit profile and in deciding which prophylactic
strategies will be used:
Frequency and pattern of recurrences
Patient’s lifestyle, compliance and willingness to commit to a
specific regimen
Plans for a pregnancy
Antimicrobial resistance and susceptibility pattern of the
organisms causing the patient’s previous UTIs
Risk of adverse events and drug allergies
4.3. Prophylaxis should only be initiated after counseling and behavior
modification have been attempted in order to minimize antibiotic
exposure and possible adverse effects.
4.4. Antibiotic prophylaxis should be limited to women with recurrent UTI
in whom non-antimicrobial strategies have not been effective and who
prefer prophylactic antimicrobial therapy.
Strong recommendation, moderate quality of evidence
5. How effective are non-antimicrobial strategies in preventing recurrent UTI?
5.1. Behavioral changes
5.1.1. Behavioral changes can be useful antimicrobial-sparing
measures in the prevention of recurrent UTI.
5.1.2. These behavioral measures include the following:
post-defecation and anal cleansing antero-posteriorly
always in women to avoid contaminating the
periurethral area with fecal flora
post-coital douche or post coital urination
liberal fluid intake especially after intercourse
avoidance of tight-fitting underwear
use of alternative form of contraception for women
using spermicide-containing contraceptives
5.2. Biologic mediators
5.2.1. Cranberry products
Cranberry juice and cranberry products are not
recommended for the prevention of urinary tract infections in
populations at risk because there is no consistent evidence as to
18
the effective amount, concentration and duration of intake of

cranberry products. The inconclusive evidence on the effect of
cranberry products in the prevention of UTI maybe due to different
PACS (proanthocyanidins) used. The recommended dose for UTI
prevention is daily consumption of 300 mL of cranberry juice
cocktail or 500 mg capsules containing 36 mg PACs) taken twice
a day as the anti-adhesion activity decreases over time. Among
patients wherein long-term antibiotic prophylaxis for recurrent
UTI is deemed necessary, the use of cranberry 500 mg capsules
containing 36 mg PAC taken twice a day can be an option to avoid
emergence of resistance of fecal and urine isolates of E. coli to
trimethoprim, amoxicillin and ciprofloxacin.
Conditional recommendation, moderate quality of evidence
5.3. Hormonal treatments in post-menopausal women
5.3.1. Application of intravaginal estriol cream once each night for two
weeks followed by twice-weekly applications for at least 8 months
OR use of an estradiol releasing silicone vaginal ring for 3 months
is recommended for the prevention of recurrent UTI in post-
menopausal women
5.3.2. Data is insufficient to recommend vaginal estrogens over
antibiotics for the prevention of recurrent UTI.
5.3.3. Low-dose oral estrogen is not recommended for the prevention of
recurrent UTI.
5.4. Immunoprophylaxis for recurrent UTI
5.4.1. Immunoprophylaxis, using immune-active E. coli fractions, is
recommended for the prevention of recurrent UTI. The dosing
regimen is once daily per orem for 3 months.
5.4.2. A longer/extended dosing regimen (once daily for 3 months, rest
for 3 months, 10 days per month for 3 months, and rest for 3
months) may be associated with a better control of recurrence in
the longer term.
Weak recommendation, moderate quality of evidence
6. How effective are antibiotic prophylactic regimens in preventing recurrent
UTI?
if the frequency of recurrence is tolerable to the patient.
6.2. If a decision is made to give antibiotic prophylaxis, either of the
following is recommended:
Continuous prophylaxis, defined as the daily intake of a low-dose
of antibiotic for 6-12 months
OR
19
Post-coital prophylaxis, defined as the intake of a single dose of

antibiotic immediately after sexual intercourse
OR
Intermittent prophylaxis, defined as self-treatment with a single
antibiotic dose based on patient’s perceived need.
6.3. Any of the antibiotics in Table 4 given either continuously for 6 to 12

months or as post-coital prophylaxis can reduce the clinical and
microbiologic recurrence of UTI episodes
Table 4. Antibiotics proven effective in reducing the number of recurrences of

UTI3,8,10,26,28,29,31,32,70,71
Antibiotics Recommended doses
Continuous Post-coital Intermittent
prophylaxis prophylaxis prophylaxis
Nitrofurantoin 50-100 mg at 50-100 mg 50 mg
bedtime
Trimethoprim 100 mg at bedtime 100 mg
Cotrimoxazole 40 mg/200 mg at 40 mg/200 mg 40 mg/200 mg
bedtime
CotrimoxazolE 40 mg/200 mg 80 mg/400 mg
3x/week
Ciprofloxacin 125 mg at bedtime 125 mg 125 mg
Norfloxacin 200 mg at bedtime 200 mg 200 mg
Ofloxacin 100 mg
Pefloxacin 400 mg weekly
Cefalexin 125-250 mg at 125-250 mg
bedtime
Cefaclor 250 mg at bedtime 250 mg
Fosfomycin 3 g every 10 days
Amoxicillin 500 mg
Cefuroxime 250 mg
7. How should individual episodes of UTI be treated in women with recurrent

UTI?
7.1. Any of the antibiotics for acute uncomplicated cystitis (Table 5) may be
used in the treatment of individual episodes of UTI in women with
recurrent UTI.
20
Table 5. Antibiotics for acute uncomplicated cystitis

Antibiotics Recommended dose and
duration
Primary Nitrofurantoin monohydrate 100 mg BID for 5 days P O
macrocrystals (not sold locally)
Nitrofurantoin macrocrystals 100 mg QID for 5 days P O
F osfomycin trometamol 3 g single dose P O
Alternative Pivmecillinam (not sold locally) 400 mg BID for 3–7 days P O
Ofloxacin 200 mg BID for 3 days P O
Ciprofloxacin 250 mg BID for 3 days P O
Ciprofloxacin extended rele ase 500 mg O D for 3 days P O
Levofloxacin 250 mg O D for 3 days P O
Norfloxacin 400 mg BID for 3 days P O
Amoxicillin-clavulanate 625 mg BID for 7 days P O
C efuroxime axetil 250 mg BID for 7 days P O
C efaclor 500 mg TID for 7 days P O
C efixime 200 mg BID for 7 days P O
C efpodoxime proxetil 100 mg BID for 7 days P O
C eftibuten 200 mg BID for 7 days P O
O NLY if with Trimethoprim-sulfamethoxa zole 160/800 mg BID for 3 days P O
proven (TMP-SMX)
susceptibility
7.2. Consider intermittent self-administered therapy in highly educated,

well-informed, motivated patients, wherein the patients are able to
recognize the characteristic signs and symptoms of UTI, are compliant
with medical instructions and have a good relationship with a medical
provider.
7.3. Breakthrough infections during prophylaxis should be treated
empirically with any of the antibiotics recommended for uncomplicated
cystitis other than the antibiotic being given for prophylaxis. Request
for a urine culture and modify the treatment accordingly.
8. How effective are non-pharmacologic interventions treating urinary tract

infections?
8.1. Cranberry juice and cranberry products are not recommended for the
treatment of urinary tract infection.
8.2. There is evidence to recommend acupuncture for prevention of
recurrent UTI among women when antibiotic prophylaxis is
contraindicated.
21
8.3. There is no available evidence to recommend coconut juice in the

prevention or treatment of UTI.
8.4. There is insufficient evidence to recommend oral water hydration (2 to
2.5 liters/day) in the prevention or treatment of UTI.
8.5. There is insufficient evidence to recommend drinking more water and
voiding before and after intercourse to prevent UTI.
22
DISCUSSION
1. How is recurrent urinary tract infection (rUTI) diagnosed?
1.1. Recurrent UTI is diagnosed when a healthy non-pregnant woman with

no known urinary tract abnormalities has 3 or more episodes of acute
uncomplicated cystitis documented by urine culture during a 12-month
period OR 2 or more episodes in a 6- month period.1-3
1.2. Recurrent UTI may either be a relapse or a reinfection. Relapse occurs

when the initial organism persists within the urinary tract and re-
emerges despite adequate treatment usually occurring 1-2 weeks after
stopping treatment. Reinfection, on the other hand, occurs when
recurrent UTI is caused by a different bacterial isolate, or by the
previously isolated bacteria after a negative intervening culture or an
adequate period (≥ 2 weeks) between infections.4,5
Summary of evidence
In a study of college women with cystitis, 25% experienced at least one
culture-confirmed recurrence within the six months following the initial infection and
2.7% had a second recurrence during this same time period. 6 A 44% recurrence rate of
UTI was reported within one year among Finnish women aged 17–82 who had E. coli
cystitis.7,8
Recurrent UTI may either be a relapse or a reinfection. Reinfection is more
common than relapse and often occurs within the first 3 months after the primary
infection. When E. coli causes the initial infection, there is a higher risk of reinfection
within the first 6 months than when the infection is caused by another pathogen. 9,10
2. Among those with recurrent UTI, who would benefit from further diagnostic
evaluation?
2.1. Routine screening for urologic abnormalities is not recommended for
the general patient population.
2.2. Screening for urologic abnormalities is recommended in the following

situations:
No response to appropriate antimicrobial therapy or rapid relapse
after such therapy
Gross hematuria during a UTI episode or persistent microscopic
hematuria
Obstructive symptoms
Clinical impression of persistent infection
Infection with urea-splitting bacteria (Proteus, Morganella,
Providencia)
History of pyelonephritis
History of or symptoms suggestive of urolithiasis
History of childhood UTI
Elevated serum creatinine
23
2.3. Patients with the above factors may benefit from further diagnostic
evaluation as these risk factors have been identified to be associated
with a higher incidence of urologic abnormalities.
2.4. All women with recurrent UTI should undergo a complete history and
physical examination to evaluate urogenital anatomy and
estrogenization of vaginal tissues and to detect prolapse. Post-void
residual urine should be measured.
Summary of evidence
The reported prevalence of urologic abnormalities in women with recurrent UTI
significant enough to warrant a change in management ranges from 0% to 6%. 11-14 A
systematic review estimated the overall prevalence at 0.8%.15 A study of 148 women,
which included only those with at least one of the factors listed above, reported a
prevalence of urologic abnormalities of 21%. 16 Because UTI during childhood is
associated with reflux nephropathy, inclusion of this factor was also recommended
although there is no data regarding its predictive value. 15
A Canadian prospective study of 186 women with recurrent UTI who underwent
cystoscopy and ultrasonography or excretory urography identified factors that would
indicate urologic evaluation.16 These include hematuria (gross hematuria and persistent
microscopic hematuria between infections), pyelonephritis and a presentation that is
not typical for simple uncomplicated UTIs (obstructive symptoms, infection with urea-
splitting bacteria, clinical impression of persistent infection or urinary calculi). Diabetes
itself did not warrant urologic evaluation.
Risk factors
In a large case-control study of women with and without a history of recurrent
UTIs, multivariate analysis showed that the frequency of sexual intercourse was the
strongest risk factor for recurrent UTI. 17 In premenopausal women, in addition to
increased frequency of intercourse, use of a spermicide and new sexual partners are
behavioral risk factors for recurrent UTI. Non-behavioral risk factors include UTI before
age 15 and a maternal history of UTI.8,10
In postmenopausal women, estrogen loss, a non-secretor status of
histocompatibility blood-group antigens and the presence of incontinence, significant
pelvic floor prolapse and an increased post-void residual urine volume increase the risk
for recurrent UTI.18 The lack of estrogen causes marked changes in the vaginal
microflora including loss of lactobacilli and increased colonization by E. coli. In a case-
control study of 149 healthy postmenopausal women with a history of recurrent UTI and
53 controls without a history of UTI, mechanical and/or physiologic factors that affect
bladder emptying were found to be strongly associated with recurrent UTIs. Multivariate
analysis showed that urinary incontinence (odds ratio 5.79), a history of UTI before
menopause (OR 4.85) and non-secretor status (OR 2.9) were the factors most strongly
associated with recurrent UTI.
Positive predictive factors for recurrent UTIs in women are symptoms after
intercourse, a prior history of pyelonephritis, absence of nocturia, and prompt resolution
of symptoms (48 hours) after initiation of treatment. The main negative predictors are
the presence of nocturia and persistence of symptoms between episodes of treated
infection.1,10
24
3. What diagnostic work-ups are indicated in women with recurrent UTI?

3.1. Radiologic or imaging studies and cystoscopy are not routinely
indicated in patients with recurrent UTI.
3.2. Renal ultrasound or CT scan/stonogram may be done to screen for

urologic abnormalities
3.3. Patients with anatomical abnormalities should be referred to a

specialist (nephrologist or urologist) for further evaluation.
Summary of evidence
In a prospective blinded observational study of 60 patients presenting for
recurrent UTI, the diagnostic yield of intravenous urography was only 8.3% (i.e, 91.7%
of the tests were negative), with an odds ratio for positive results at 0.22 (95% CI, 0.08-
0.62).20
A prospective study of 100 young women for the evaluation of recurrent UTI
was done in urologic departments in The Netherlands. 21 These women underwent a
standardized workup consisting of a voiding diary, urinalysis and culture, abdominal x-
ray with ultrasound or intravenous urography and cystoscopy. The radiologic studies
revealed only one relevant abnormality.
However, in a database review which included 118 women with recurrent UTI
who underwent cystoscopy, nine (8%) patients had significant findings. 22 Patients who
were older than 50 years were associated with a higher risk of having a positive finding.
Most studies report urologic abnormalities identified from intravenous
pyelography (IVP). However, IVP can cause mild generalized reactions
(hypersensitivity reactions, nausea, vomiting and syncope) in 5 to 10% of patients. In
one study where 120 women underwent both IVP and renal ultrasound (RUS), there
was good agreement between the two modalities for diagnosis of hydronephrosis
(kappa = 0.91) but less agreement in the diagnosis of major pyelonephritis changes
(kappa = 0. 79), ureteric calculi and renal calculi >5 mm (kappa =0. 78) and expansile
lesions (kappa = 0.38).23 In a study of 94 women with a history of UTI referred by their
physician for IVP or RUS, the RUS and plain abdominal radiograph findings were
compared with IVP and the only disagreement was in one patient where RUS detected
a 1.5 cm intrarenal mass not seen on IVP.24 In another study comparing combined
ultrasound and plain abdominal radiograph with IVP performed on 89 women and 69
men with a history of UTI, the two modalities concurred in 152 of the 158 patients. RUS
and plain film did not detect duplex kidney, small bladder diverticula, papillary necrosis
and mild bilateral hydroureter of unexplained etiology. 25
4. When is prophylaxis for recurrent UTI indicated?

25
according to patient preference if the frequency of recurrence is

tolerable to the patient.
4.2. The following factors should guide the physician in determining the
patient’s risk-benefit profile and in deciding which prophylactic
strategies will be used:
Frequency and pattern of recurrences
Patient’s lifestyle, compliance and willingness to commit to a
specific regimen
Plans for a pregnancy
Antimicrobial resistance and susceptibility pattern of the
organisms causing the patient’s previous UTIs
Risk of adverse events and drug allergies
4.3. Prophylaxis should only be initiated after counseling and behavior
modification have been attempted in order to minimize antibiotic
exposure and possible adverse effects.
4.4. Antibiotic prophylaxis should be limited to women with recurrent UTI
in whom non-antimicrobial strategies have not been effective and who
prefer prophylactic antimicrobial therapy.
Summary of Evidence
Burden
The estimated burden of recurrent UTI is 1 in 4 women will have a recurrence
within a year. Each episode of UTI is associated with 6 days of symptoms, 2 days of
restricted activity, one day absence from work or class and a half day in bed.
Benefits
Although long-term sequelae such as renal failure, genitourinary cancer or
increased mortality have not been reported from recurrent UTI, a woman with frequent
recurrent urinary infection may experience substantial social and professional
disruption attributable to symptomatic episodes. 4 Women who experience acute
uncomplicated urinary infection are also at risk for acute non-obstructive
pyelonephritis.17 Therefore, the decision to give prophylaxis rests more on weighing the
benefit of alleviating the discomfort of UTI and avoiding the inconveniences associated
with recurrent episodes versus the potential harm of antibiotic prophylaxis and
emergence of resistant strains. The goal of long-term management of recurrent UTI
should be to improve the quality of life while minimizing antimicrobial exposure. 3
Patients should be counseled about the pros and cons of various prophylactic strategies
and the decision to give prophylaxis should be individualized for each patient.
Antibiotic prophylaxis has been shown to reduce the risk of recurrence by
approximately 95%.26,27 Its use should be limited to women with recurrent UTI in whom
non-antimicrobial strategies have not been effective and who prefer prophylactic
antimicrobial therapy.
26
Risk factors
In a large case-control study of women with and without a history of recurrent
UTIs, multivariate analysis showed that the frequency of sexual intercourse was the
strongest risk factor for recurrent UTI. 17 In premenopausal women, in addition to
increased frequency of intercourse, use of a spermicide and new sexual partners are
behavioral risk factors for recurrent UTI. Non-behavioral risk factors include UTI before
age 15 and a maternal history of UTI.8,10
In postmenopausal women, estrogen loss, a non-secretor status of
histocompatibility blood-group antigens and the presence of incontinence, significant
pelvic floor prolapse and an increased post-void residual urine volume increase the risk
for recurrent UTI.18 The lack of estrogen causes marked changes in the vaginal
microflora including loss of lactobacilli and increased colonization by E. coli. In a case-
control study of 149 healthy postmenopausal women with a history of recurrent UTI and
53 controls without a history of UTI, mechanical and/or physiologic factors that affect
bladder emptying were found to be strongly associated with recurrent UTIs. Multivariate
analysis showed that urinary incontinence (odds ratio 5.79), a history of UTI before
menopause (OR 4.85) and non-secretor status (OR 2.9) were the factors most strongly
associated with recurrent UTI.17
Harms
The reported incidence of adverse drug effects with antibiotic prophylaxis
ranges from 1.3% to 20%.28-33 In the Cochrane review by Albert 2004, all trials reported
severe side effects necessitating withdrawal of antibiotic therapy, with a pooled RR of
1.58 (95% CI 0.47– 5.28), favoring the placebo group.34 The most common described
severe side effects were skin rash and nausea. The RR of having one side effect not
requiring antibiotic withdrawal was 1.78 (95% CI 1.06 – 3.00) again favoring the placebo
group. Most of the antibiotics used for antibiotic prophylaxis of recurrent UTI are also
associated with a risk for acquiring Clostridium difficile-associated diarrhea (CDAD).
This risk should be discussed with patients and patients with a history of recurrent
CDAD should be offered non-antimicrobial preventive approaches.8
A surveillance study of antimicrobial resistance in women with cystitis from
Europe and Brazil showed high rates of resistance to E. coli isolates, 29% for
trimethoprim-sulfamethoxazole (cotrimoxazole) and 8% for fluoroquinolones.35 In
another study evaluating 2,478 E. coli isolates, the most common pattern of multi-
resistance for E. coli isolates was for ampicillin/sulfamethoxazole (8.7% of strains),
followed by ampicllin/sulfamethoxazole/trimethoprim/cotrimoxazole resistance (6.4% of
all strains.). It was also noted that, with the exception of fosfomycin, resistance to any
antibiotic agent is associated with an increased resistance to other antibiotic agents
tested.36
Costs
Another relevant issue is cost-effectiveness of prophylaxis versus treating
individual episodes of recurrent UTI. A cost-effectiveness study done in the United
States in 1981 concluded that continuous prophylaxis with cotrimoxazole was more
cost-effective than treating individual episodes. 37 However, these results cannot be
directly applied in our setting because of differences in costs of physician charges,
medications and extent of laboratory work-up.
27
5. How effective are non-antimicrobial strategies in preventing recurrent UTI?

5.1. Behavioral changes
5.1.1. Behavioral changes can be useful antimicrobial-sparing
measures in the prevention of recurrent UTI.
5.1.2. These behavioral measures include the following:

post-defecation and anal cleansing antero-posteriorly
always in women to avoid contaminating the
periurethral area with fecal flora
post-coital douche or post coital urination
liberal fluid intake especially after intercourse
avoidance of tight-fitting underwear
use of alternative form of contraception for women
using spermicide-containing contraceptives
Summary of Evidence
There are no randomized trials regarding lifestyle modifications in preventing
recurrent UTI. However, based on reviews and recommendations by various authors,
they may be an important cornerstone of prevention since they carry a low risk of
adverse effects.3,10,38
5.2. Biologic mediators

5.2.1. Cranberry products
Cranberry juice and cranberry products are not
recommended for the prevention of urinary tract infections in
populations at risk because there is no consistent evidence as to the
effective amount, concentration and duration of intake of cranberry
products. The inconclusive evidence on the effect of cranberry products
in the prevention of UTI maybe due to different PACS
(proanthocyanidins) used. The recommended dose for UTI prevention is
daily consumption of 300 mL of cranberry juice cocktail or 500 mg
capsules containing 36 mg PACs) taken twice a day as the anti-adhesion
activity decreases over time.
Among patients wherein long-term antibiotic prophylaxis
for recurrent UTI is deemed necessary, the use of cranberry 500 mg
capsules containing 36 mg PAC taken twice a day can be an option to
avoid emergence of resistance of fecal and urine isolates of E. coli to
trimethoprim, amoxicillin and ciprofloxacin.
Conditional recommendation, moderate quality of evidence
Summary of evidence
Benefits
Cranberries contain condensed tannins called proanthocyanidins, which
prevent fimbriated E. coli from adhering to uroepithelial cells in the urinary tract. The
antiadhesive property of cranberry probably helps prevent UTI by directly preventing
E.coli from adhering to uroepithelial cells and by selecting for less adherent bacterial
strains in the stool.39
28
A recent Cochrane review of 6 cross-over studies, 11 parallel group studies

with two arms; 5 with three arms, and 2 studies with a factorial design with a total of
4,473 participants assessed the effectiveness of cranberry products in preventing UTIs
in susceptible populations.40 It included studies comparing cranberry products to
placebo, no treatment, water, methenamine hippurate, antibiotics, and Lactobacillus.
RCTs cited in the 2004 UTI guideline development were included in this recent
review.41-43
Cranberry versus placebo

The meta-analyses of 13 studies (2380 participants) showed that cranberry
products did not significantly reduce the occurrence of symptomatic UTI compared to
placebo, water or no treatment (RR 0.86, 95% CI 0.71 to 1.04). Subgroup analysis also
failed to show significant reduction in UTI among women with recurrent UTIs (RR 0.74,
95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women
(RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to
1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); and people with neuropathic
bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20).
Cranberry versus antibiotics

Meta-analysis of two RCTs comparing the effectiveness of cranberry
capsules with antibiotics in women showed that cranberry capsules did not significantly
reduce the risk of repeat UTI (RR 1.31, 95% CI 0.85 to 2.02) compared to low-dose
cotrimoxazole.44,45 The NAPRUTI RCT among 221 premenopausal women showed that
the proportion with at least 1 symptomatic UTI during the 1-year study period was
slightly greater in the cranberry than in the cotrimoxazole group (78.2% versus
71.1%).45 However, there were more fecal and urine resistant E. coli isolates in the
cotrimoxazole (86.3 %) than in the cranberry arm (23.7%). Similar pattern of resistance
was seen on trimethoprim, ciprofloxacin, and amoxicillin as early as 1 month of
prophylactic treatment with cotrimoxazole.
Cranberry versus Lactobacillus

The RCT by Kontiokari (2001) compared cranberry-lingonberry juice 50 ml
daily for 6 months, lactobacillus drink 5 days a week for one year, and placebo for the
first recurrence of symptomatic UTI among 150 women who had E.coli infections.42
Thirteen women dropped out from the study: four (8%) each in the cranberry and
lactobacillus group and five (10%) in the control group usually because of change in
residence. The RCT showed that regular drinking of cranberry juice significantly
reduced the recurrence of UTI compared with the control group at 6 months (ARR 20%,
95% CI 3% to 36%; NNT 5, 95% CI 3 to 34). At 12 months, there was no significant
reduction in the recurrence of UTI in the cranberry group compared to the control group
(ARR 14%, 95% CI –4%, 32%). On intention-to-treat analysis, the significant reduction
in UTI was not maintained (ARR 12%, 95% CI -4%, 28%).
29
Harms
Dropout rates in several studies were high (20-55%). Common reasons for
withdrawal were the taste, caloric load, and high cost of cranberry. 40,42 One study
warned that ingesting large amounts of cranberries over a long duration may increase
the risk of some types of urinary stones in high-risk patients because of the increased
urinary excretion of oxalate and slight urinary acidification. 46 Gastrointestinal effects
such as hearburn, vomiting, diarrhea, and gastroenteritis were the common adverse
effects reported in several studies included in the recent Cochrane review. 40
Costs
The mean annual cost of prophylaxis was Can$ 624 for cranberry tablets and
Can$ 1,400 for cranberry juice.43 Cost savings were highest when patients experienced
>2 UTIs per year and had >2 days of missed work. Total antibiotic consumption was
less annually in both treatment groups compared with placebo. Cost effectiveness
ratios demonstrated cranberry tablets were twice as cost-effective as organic juice for
prevention. In this single trial that evaluated the issue of cost, Stothers (2002) concluded
that cranberry tablets are more cost-effective than organic cranberry juice for the
prevention of UTI.
Comments
While the RCT by Stothers provides some evidence that cranberry tablet or
capsule is a cost-effective option in the prevention of UTI, it is the consensus of the task
force that cranberry juice or any of its products cannot be recommended at this time
because there is no consistent evidence as to the effective amount, concentration and
duration of intake of cranberry products. The recommended amount for UTI prevention
is daily consumption of 300 mL of cranberry juice cocktail or capsules containing 36 mg
PACs (proanthocyanidins) taken twice a day as the anti-adhesion activity decreases
over time.46 Furthermore, high withdrawal rates in most of the trials (20%-55%) suggest
that long-term adherence may be difficult to achieve for long periods.
Table 3. Available cranberry products in the Philippines

Product Components PAC component Price per bottle
Cranbiotics Cranberry extract 120 mg P615/60 caps
(Futurebiotics) Lactobacillus (standardized for
sporogenes 30% PACs)
CranRx Cranberry extract 500 mg (3X more P400/30 caps
(Natures way) Standardized PACs)
Cranberry Cranberry conc 5,600 mg (700 mg - P410/90 caps
concentrate Vit C 8:1 extract) whole
(NOW foods) Sugar cranberries
Cranberry GNC Cranberry Fruit 500 mg P1,160
Powder
Fontana cranberry Cranberry NS P84/ 1L
juice Vit C
30
5.2.2. Probiotic lactobacilli

Lactobacilli both in oral form and vaginal suppositories are not
recommended in the prevention of UTI.
Summary of evidence
Benefits
A recent RCT on 252 postmenopausal women with recurrent UTIs comparing
low-dose once daily cotrimoxazole and twice daily oral capsules of Lactobacillus
rhamnosus GR-1 and Lactobacillus reuteri RC-14 showed that after 12 months of
prophylaxis, the mean number of clinical recurrence (2.9, 95% CI, 2.3 to 3.6) did not
differ significantly between the antibiotic group (3.3 95% CI, 2.7 to 4.0) and the
lactobacilli group (p=0.42).48 The mean number of microbiologic recurrence and
asymptomatic bacteriuria was 1.2 (95% CI, 0.9-1.6) in the cotrimoxazole group and 1.8
(95% CI, 1.4-2.3) in the lactobacilli group (p=0.02). The resistance to cotrimoxazole,
trimethoprim, and amoxicillin increased from approximately 20% to 40% and
approximately 80% to 95% in E. coli from the feces and urine of asymptomatic women
and among E. coli causing a UTI among women after 1 month of cotrimoxazole
prophylaxis.
One hundred young women with a history of recurrent UTI treated with
antibiotics were randomized to receive an intra-vaginal capsule of Lactobacillus
crispatus (Lactin-V) or placebo daily for 5 days then once weekly for 10 weeks. The
study showed that recurrent UTI occurred in 15% of women receiving Lactin-V
compared with 27% of women receiving placebo (RR 0.5 95% CI, 0.2–1.2).49
Other clinical trials of lactobacilli to prevent recurrent UTI were small and have
not shown a benefit for lactobacilli over other preventive treatments or placebo based
on a review done by Barrons, et al in 2008. 50
Comments
It is important to understand the characteristics of the particular strain being
promoted as a probiotic to prevent UTIs. L. rhamnosus GR-1 is reported to contain key
beneficial characteristics for candidate probiotic strains, namely highly effective
adherence to vaginal epithelial cells, inhibitory to adherence of uropathogens, and
growth inhibitory for pathogens of the urogenital tract. The other component, L
fermentum RC-14 produces H2O2 and a biosurfactant and is highly adherent. Currently
there are no adequately studied probiotic products for preventing UTIs. Multiple
problems exist for the development of such a product (identifying specific strains that
colonize and inhibit uropathogen colonization of the vagina and survive storage and
administration) especially if taken orally, which require passage through the gut. 51
5.3. Hormonal treatments in post-menopausal women

Application of intravaginal estriol cream once each night for two weeks
followed by twice-weekly applications for at least 8 months OR use of
an estradiol releasing silicone vaginal ring for 3 months is
recommended for the prevention of recurrent UTI in post-menopausal
women
31
Summary of Evidence
Vaginal estrogen versus placebo
Benefits
A Cochrane systematic review investigated the efficacy and safety of estrogens for
preventing recurrent UTI in post-menopausal women.52 Two studies used vaginal
estrogens; however, the authors did not pool these studies due to significant
heterogeneity attributed to the varying type of application method used. 53,54 Raz 1993
compared topically applied intravaginal oestriol cream to placebo cream while Eriksen
1999 compared releasing silicone vaginal ring (containing 2 mg oestriol) with a no
treatment control group.
In the study by Raz 1993, the use of intravaginal oestriol cream significantly reduced
the rate of symptomatic UTI episodes (0.5 episodes per patient year in the oestriol
group versus 5.9 in the control group, p<0.001). 53 In addition, the estrogen group had
a cumulative likelihood of remaining disease free compared to the placebo group (0.95
versus 0.30, p<0.001) and had less antibiotic days than the placebo group (6.9 +/- 1.1
days versus 32.0 +/- 7.8 days, p<0.001) In the Eriksen 1999 study, use of a vaginal ring
significantly reduced the rate of UTI by 36%.54 Eriksen also reported that after 9 months,
45% of participants were free of UTI in the estrogen group versus 20% in the control
group (p<0.008).
Harms
Adverse events reported by patients receiving vaginal estrogens and placebo included
vaginal bleeding and non-physiologic discharge, and vaginal irritation, burning, or
itching.53,54 Based on the systematic review mentioned, there was no significant
difference in adverse events between the groups treated with vaginal estrogens or
placebo cream (RR 4.72, 95% CI 0.67 - 33.53; I2 = 67.5%).
5.3.1. Data is insufficient to recommend vaginal estrogens over

antibiotics for the prevention of recurrent UTI.
Summary of evidence
Vaginal estrogen versus Antibiotics
Benefits
In the same Cochrane review by Perrotta 2008, two small studies compared
vaginal estrogens and antibiotics, but the studies used different modes of estriol
administration and different antibiotic comparators.52 The Raz 2003 study used a
vaginal pessary against oral nitrofurantoin while the Xu 2001 study used a vaginal
cream against oral ofloxacin.55,56 These two studies had conflicting results. In the Raz
2003 study involving 171 patients, the antibiotic group reported significantly less UTIs
than the estrogen group after 3 months (RR 1.30, 95% CI 1.01 – 1.68 ).55 On the other
hand, the Xu 2001 study involving 45 patients reported significantly less UTIs in the
estrogen group compared to the antibiotic group (RR 0.09, 95% CI 0.02 – 0.36).56
32
However, there was no significant difference in the number of women with recurrent
UTI two months after stopping treatment (RR 0.56, 95% CI 0.09 – 3.5
Harms
In the study by Xu 2001, burning and itching were reported in the estrogen
group. No side effects were reported for the antibiotic group. 56 In the study by Raz 2003
the adverse events were more frequent in the vaginal estrogen group necessitating
dropouts (27/86 from the estrogen group and 23/85 from the nitrofurantoin group). 55
These included itching, burning, vaginal discharge and metrorrhagia in the estrogen
group and fever, gastrointestinal upsets and urticaria in the nitrofurantoin group. When
pooled, the RR for adverse events was 12.86 (95% CI 1.75 – 94.29)
5.3.2. Low-dose oral estrogen is not recommended for the prevention of

recurrent UTI.
Summary of evidence
Benefits
Estrogen therapy is associated with a return of the premenopausal lactobacillus-
dominated vaginal flora, acid vaginal pH and reduced vaginal colonization with
organisms, all of which account for the decreased risk of UTI. A systematic review by
Perrotta 2008 included four studies involving 2798 women and compared oral
estrogens with placebo.52,57-60 There was no significant difference in the number of
women with UTI at the end of the treatment period (RR 1.08, 95% CI 0.88 to 1.33; I2 =
0%).
Harms
In the same systematic review by Perrotta 2008, there were only two studies
that reported adverse events.52 Cardozo 1998 reported breast tenderness and mild
vaginal bleeding, and Ouslander 2001 reported vaginal spotting and mild breast
discomfort.58,60 There were significantly less adverse events in the placebo group (2
studies, 104 women: RR 5.11, 95% CI 1.39 to 18.76; I 2 = 0%).
Adhesion blockers
UTIs caused by E. coli are initiated by adhesion of the bacteria to mannosylated
receptors in the uroepithelium by means of FimH adhesin located on type 1 pili;
theoretically, mannosides could block adhesion. D-mannose, available in health-food
stores, may block adhesion; however, it has not been evaluated in clinical trials. 3
5.4. Immunoprophylaxis for recurrent UTI

5.4.1. Immunoprophylaxis, using immune-active E. coli fractions, is
recommended for the prevention of recurrent UTI. The dosing
regimen is once daily per orem for 3 months.
33
Summary of evidence
Immunotherapy/immunoprophylaxis involves the administration of lyophilized
bacterial lysates from 18 E. coli strains most frequently responsible for UTI, which then
acts as an immunostimulant. Exposure to the immunostimulant enhances the patient’s
innate and adaptive immune system of the urinary tract mucosa causing it to promptly
react to pathogenic E. coli.
The bacterial extract activates T-helper cells and stimulates the proliferation and
activity of T and B lymphocytes, which migrate to the mucosal-associated lymphoid
tissue of the urinary tract. These cells secrete increased levels of immunoglobulin A
(sIgA) specific to the E. coli fragments. Administration of the vaccine also causes
increased levels of bladder IFN-y and IL6 levels and upregulation of the PMN killing
activity.
Three meta-analyses of 5 studies consistently demonstrated the effectiveness of
immunoprophylaxis compared to placebo in preventing symptomatic bacteriuria,
decreasing the episodes of dysuria, asymptomatic bacteriuria and the use of
antibiotics.61-63
Pooled analysis of 6 RCTs showed that immunoprophylaxis significantly reduced
the risk of recurrent UTI by 40% (RR = 0.60, 95% CI 0.53, 0.68). 64-69
Limited information on adverse events from the RCTs showed good tolerability
profile for immunoprophylaxis. Few adverse events were reported including pruritus,
diarrhea, and headache with flushing. Adverse event rates ranged from 2.3 to 5.4%.
The six RCTs were of fair methodological quality. Most were properly randomized
trials with adequate allocation methods. Most had sufficient blinding. Nearly all trials
had significant patient drop out but these were in equal proportion across treatment
groups. The results across the 6 trials were consistent. High value was given to
reduction of recurrence.
No cost-effectiveness studies have been published to compare
immunoprophylaxis versus treatment of individual UTI episodes.
5.4.2. A longer/extended dosing regimen (once daily for 3 months, rest

for 3 months, 10 days per month for 3 months, and rest for 3
months) may be associated with a better control of recurrence in
the longer term.
Weak recommendation, moderate quality of evidence
Summary of evidence
One RCT using an extended dosing regimen showed greater reduction in recurrent
infection at the 6 month period compared to other RCTs using the once-daily dosing for
3 months. Adverse events associated with the extended regimen were minor. 68 The
single RCT using the extended dosing regimen was a double blinded trial with proper
randomization and adequate allocation concealment. However, the value of greater
reduction of the risk, compared to the cost and inconvenience of extended/intensified
treatment regimen needs to be considered. There is a need to assess the justification
of higher cost of treatment with the risk and expected cost of a recurrent UTI.
6. How effective are antibiotic prophylactic regimens in preventing recurrent

UTI?
34

if the frequency of recurrence is tolerable to the patient.
6.2. If a decision is made to give antibiotic prophylaxis, either of the
following is recommended:
Continuous prophylaxis, defined as the daily intake of a low-dose
of antibiotic for 6-12 months
OR
Post-coital prophylaxis, defined as the intake of a single dose of
antibiotic immediately after sexual intercourse
OR
Intermittent prophylaxis, defined as self-treatment with a single
antibiotic dose based on patient’s perceived need.
6.3. Any of the antibiotics in Table 4 given either continuously for 6 to 12
months or as post-coital prophylaxis can reduce the clinical and
microbiologic recurrence of UTI episodes
Table 4. Antibiotics proven effective in reducing the number of recurrences of

UTI3,8,10,26,28,29,31,32,70,71
Antibiotics Recommended doses
Continuous Post-coital Intermittent
prophylaxis prophylaxis prophylaxis
Nitrofurantoin 50-100 mg at 50-100 mg 50 mg
bedtime
Trimethoprim 100 mg at bedtime 100 mg
Cotrimoxazole 40 mg/200 mg at 40 mg/200 mg 40 mg/200 mg
bedtime
CotrimoxazolE 40 mg/200 mg 80 mg/400 mg
3x/week
Ciprofloxacin 125 mg at bedtime 125 mg 125 mg
Norfloxacin 200 mg at bedtime 200 mg 200 mg
Ofloxacin 100 mg
Pefloxacin 400 mg weekly
Cefalexin 125-250 mg at 125-250 mg
bedtime
Cefaclor 250 mg at bedtime 250 mg
Fosfomycin 3 g every 10 days
Amoxicillin 500 mg
Cefuroxime 250 mg
Summary of evidence
Continuous antibiotic prophylaxis versus placebo
An updated Cochrane systematic review of 10 RCTs (N=430 premenopausal
35
and postmenopausal women) showed that continuous antibiotic prophylaxis for 6-12
months reduced the number of clinical and microbiological recurrences of UTI
compared to placebo.2 During active prophylaxis the rate of microbiological
recurrence/person-year was 0 to 0.9 episodes in the antibiotic group versus 0.8 to 3.6
episodes in the placebo group. The RR of having one microbiological recurrence was
0.21 (95% CI 0.13 - 0.34) favoring antibiotic prophylaxis with NNT=1.85. The RR for
clinical recurrence was 0.15 (95% CI 0.08 - 0.28). After prophylaxis, no difference in
microbiological recurrence was seen in 2 studies (RR 0.82; 95% CI 0.44 - 1.53). There
were more adverse events in the antibiotic group (RR 1.78; 95% CI 1.06 - 3.00).
Adverse effects included vaginal and oral candidiasis, skin rash and nausea. Antibiotics
included in this review were cotrimoxazole, nitrofurantoin, cephalexin and ciprofloxacin.
Continuous antibiotic prophylaxis versus another antibiotic regimen

Six RCTs (N=458 premenopausal and postmenopausal women) comparing
different antibiotic regimens versus each other were included in the Cochrane review. 2
Results were not pooled because of significant heterogeneity. Individual results of the
studies showed no significant differences in infection rates over 6-12 months with one
antibiotic over another.28,29,32,72-74 Antibiotics compared were nitrofurantoin, norfloxacin,
cefaclor, trimethoprim, cotrimoxazole, and ciprofloxacin. The only trial that showed a
difference compared nitrofurantoin 100 mg once daily with trimethoprim 100 mg once
daily with a RR for microbiologic recurrence of 3.58 (95% CI 1.33-9.66) and a RR for
clinical recurrence of 1.72 (95% CI 1.06, 2.79) favoring nitrofurantoin.
In the 6-month period after discontinuation of the 6-month prophylaxis, 48% of
patients in the treatment groups developed at least one episode of UTI, a rate similar
to that of the placebo group.32 One other trial with a 6-month prophylaxis had similar
results.75 In one trial of 12-month prophylaxis, the authors report that 69% maintained
improvement after discontinuation of prophylaxis but no details were provided. 29
Continuous antibiotic prophylaxis versus non-antibiotics

The Cochrane review of Albert 2004 evaluated 2 studies that compared
antibiotics (nitrofurantoin, trimethoprim) with methenamine hippurate and 1 study that
compared trimethoprim with povidone iodine. 34 Only one study favored antibiotic
prophylaxis in reducing recurrence of UTI. The Brumfitt 1981 study involving 99 patients
(43 with nitrofurantoin, 56 with methenamine hippurate) showed that nitrofurantoin 50
mg every 12 hours prevented recurrence of UTI compared to methenamine hippurate
with an RR of 0.7 (95% CI 0.10 – 0.75) favoring nitrofurantoin.76
Post-coital prophylaxis versus placebo

Post-coital administration of cotrimoxazole (40 mg/200 mg as a single
dose) given for 6 months was compared with placebo in a randomized controlled trial
of 28 women regardless of whether their UTI episodes were temporally related to sexual
intercourse or not. The proportion of patients who developed UTI was 75% in the
placebo group and 12% in the post-coital prophylaxis group.33
Continuous antibiotic prophylaxis versus post-coital prophylaxis

One RCT comparing post-coital versus continuous daily ciprofloxacin found
no significant difference in rates of positive urine culture after 1 year (RR 0.9; 95% CI
0.55, 1.45); but the rate of discontinuance due to adverse drug reaction was higher in
36
the continuous prophylaxis group (5.35%) compared to the postcoital prophylaxis group
(1.3%).30 Continued suppression of gram-negative introital flora in 36% of women within
one year of stopping continuous or postcoital ciprofloxacin prophylaxis was reported
but there was no clinical correlation with actual episodes of urinary tract infection.
Continuous antibiotic prophylaxis versus intermittent prophylaxis

A recent RCT compared the effectiveness and safety of patient-initiated single
dose (intermittent) against continuous low-dose antibiotic prophylaxis for post-
menopausal women.71 In the intermittent antibiotic group, a single-dose antibiotic was
taken by patients every time they were exposed to conditions predisposing to UTI based
on the patients’ previous experience – such as, sexual intercourse, travelling, working
or walking for a long time, emiction holdback, diarrhea or constipation. For each
antibiotic, only one specific dose was used for all patients. They used any one of the
following antibiotics based on previous antimicrobial susceptibility testing: furantoin 50
mg, sulphamethazine-trimethoprim 200/40 mg, norfloxacin 200 mg, ciprofloxacin 125
mg, amoxicillin 500 mg, cefaclor 250 mg or cefuroxime 250 mg.
Recurrent UTI episodes in both groups were significantly reduced (5.1 to 1.9
episodes/patient per year in the Intermittent Group (p<0.001) and from 4.7 to 1.4
episodes/patient year (p<0.001], in the Continuous Group). 71 The difference between
the two groups was not statistically significant; however, the proportion of patients
experiencing 0 or 1 episode of UTI per year in the continuous group was significantly
higher than in the intermittent group (59.4% versus 35.5%; p<0.05).
On the other hand, the incidence of any adverse event in the continuous group
was significantly higher than that in the intermittent group (92.5% versus 63.6%,
p<0.05).71 The continuous group had significantly higher gastrointestinal events
compared with the continuous group (30.0% versus 9.1%, p<0.05), with a relative risk
of 4.0 (95% CI 1.02 - 15.73; p=0.045, Fisher’s exact test. In this study, the frequency of
antibiotic used for the Intermittent group was 40.7 +/- 16.2 times/patient year, or
approximately once a week, providing evidence that perhaps weekly prophylaxis may
be as effective as daily prophylaxis. This study however is limited by its small sample
size as <40 patients/group were included in the final analysis due to drop-outs (eight
for the intermittent group and two for the continuous group).
Comments
Low-dose prophylaxis with antimicrobial agents that are concentrated in the
urine can achieve inhibitory drug levels in the urine and prevent introduced bacteria
from multiplying and colonizing the vagina. Sub-inhibitory drug levels may also
decrease the expression of bacterial virulence factors and reduce fecal and vaginal
reservoirs of E. coli.
It is important to determine if a patient will be able to comply with the
recommended prophylactic regimen. In a retrospective cohort, compliance was the
most important determinant of success of prophylaxis (OR 0.074; p<0.0001). Among
the 51/181 subjects with failure of prophylaxis, 26/51 developed resistance to the
administered agent.77 In one study of long-term prophylaxis with cefaclor or
nitrofurantoin, patients reported lack of compliance shortly before the onset of an
episode of bacteriuria with cultures reporting susceptible strains. 28
37
Comparative effectiveness of prevention strategies

A well-organized decision analysis using a Markov Chain Monte Carlo model
compared the cost-effectiveness of 5 strategies in reducing recurrent UTI in women.
The strategies evaluated were: nitrofurantoin prophylaxis, topical estrogen prophylaxis,
daily cranberry prophylaxis, monthly acupuncture sessions and self-directed treatment
with ciprofloxacin at the earliest symptom. The decision analysis showed that daily
prophylactic use of nitrofurantoin resulted in the lowest number of UTIs per year (0.4)
and the highest payer cost, but with the most quality-adjusted life days gained (QALDs)
per year. Acupuncture resulted in the second-highest QALDs gained and decreased
UTIs to 0.7 but this may be due to publication bias due to limited studies on
acupuncture. Symptomatic self-treatment was the cheapest to both payers and
patients due to decreased utilization of the health care system but no significant QALD
was gained because the number of UTIs per year was not reduced. While daily
antibiotic use is the most studied and effective prevention strategy, the impact of
prolonged antibiotic use on antimicrobial resistance and antibiotic-related adverse
events needs to be considered compared to non-antimicrobial strategies. Hence,
clinicians may consider a combination of antimicrobial and non-antimicrobial prevention
strategies depending on the patients’ beliefs, preferences and values. 91, 92
7. How should individual episodes of UTI be treated in women with recurrent

UTI?
7.1. Any of the antibiotics for acute uncomplicated cystitis (Table 5) may be
used in the treatment of individual episodes of UTI in women with
recurrent UTI.
7.2. Consider intermittent self-administered therapy in highly educated,

well-informed, motivated patients, wherein the patients are able to
recognize the characteristic signs and symptoms of UTI, are compliant
with medical instructions and have a good relationship with a medical
provider.
Breakthrough infections during prophylaxis should be treated

empirically with any of the antibiotics recommended for uncomplicated
cystitis other than the antibiotic being given for prophylaxis. Request
for a urine culture and modify the treatment accordingly.
38
Table 5. Antibiotics for acute uncomplicated cystitis

Antibiotics Recommended dose and
duration
Primary Nitrofurantoin monohydrate 100 mg BID for 5 days P O
macrocrystals (not sold locally)
Nitrofurantoin macrocrystals 100 mg QID for 5 days P O
F osfomycin trometamol 3 g single dose P O
Alternative Pivmecillinam (not sold locally) 400 mg BID for 3–7 days P O
Ofloxacin 200 mg BID for 3 days P O
Ciprofloxacin 250 mg BID for 3 days P O
Ciprofloxacin extended rele ase 500 mg O D for 3 days P O
Levofloxacin 250 mg O D for 3 days P O
Norfloxacin 400 mg BID for 3 days P O
Amoxicillin-clavulanate 625 mg BID for 7 days P O
C efuroxime axetil 250 mg BID for 7 days P O
C efaclor 500 mg TID for 7 days P O
C efixime 200 mg BID for 7 days P O
C efpodoxime proxetil 100 mg BID for 7 days P O
C eftibuten 200 mg BID for 7 days P O
O NLY if with Trimethoprim-sulfamethoxa zole 160/800 mg BID for 3 days P O
proven (TMP-SMX)
susceptibility
Summary of evidence
Benefits
Clinical trials on the treatment of individual episodes in recurrent UTI are
limited. Amoxicillin-clavulanate, cephradine, ciprofloxacin and lomefloxacin have all
been found to be effective.78,79 There are no published trials on 3-dav therapy for
individual episodes of recurrent UTI in women. However, given the evidence that the
microbial flora encountered in patients with recurrent UTI are similar to those in women
with uncomplicated UTI where 3-day therapy is considered acceptable, it is very likely
that 3-day or 7-day therapy with any of the antibiotics recommended for simple
uncomplicated UTI will also be effective in this setting.
In a trial where 38 patients with recurrent UTI were randomized to receive
either continuous prophylaxis with cotrimoxazole or intermittent self-administered
therapy with cotrimoxazole, 92% of symptomatic episodes in the self-therapy group
were confirmed microbiologically and 86% of the infections responded to the single
dose treatment.80 The infection rate for those on prophylaxis was 0.2 episodes per
patient year compared to 2.2 episodes per patient year for patients on intermittent self-
therapy (p<0.001). Among those that did not respond or relapsed, none evolved into
pyelonephritis and all were cured by a second longer course of therapy. In the self-
treatment group, UTI was correctly diagnosed in 35/38 patients and self-treatment was
effective in 30/35 infections. In a later study by Schaeffer and Stuppy 1999, among 34
women with a cumulative of 84 symptomatic UTI episodes, 78/84 (92%) responded
clinically to self-treatment.81 A study by Gupta 2001 showed similar results, the women
39
were highly accurate in identifying the presence of significant bacteriuria based on their
voiding symptoms and no serious events were noted. 8,82
Self-administered antibiotic therapy reduces the time between onset of
symptoms and initiation of treatment; avoids the inconvenience and cost of a clinic visit
compared with the standard physician-directed treatment. This also minimizes
exposure to antimicrobial agents compared to continuous or postcoital prophylaxis.83
However, use of this strategy should be limited to women with clearly documented
recurrent infections and who are motivated, compliant with medical instructions and
have a good relationship with a medical provider. 8
Harms
Five and 3 patients developed side effects in the prophylaxis and self-therapy
groups, respectively.80 The reported incidence of infections with organisms resistant to
antibiotic being used for prophylaxis ranged from 12% for cotrimoxazole, 50% for
norfloxacin, 54% for cefaclor, and 58% for nitrofurantoin.28,29
Costs
Annual direct costs per person in the prophylaxis group were $256 versus
$239 in the self-therapy group. The authors cautioned, however, that their population
was a select group of women, many of whom had attended a special clinic on UTI and
were sufficiently motivated to enroll in a long-term clinical study.80
8. How effective are non-pharmacologic interventions treating urinary tract

infections?
8.1. Cranberry juice and cranberry products are not recommended for the
treatment of urinary tract infection.
Summary of evidence
A recent Cochrane systematic review found no properly randomized
controlled trials assessing the effectiveness of cranberry juice for the
treatment of UTI.84 The review excluded two crossover trials because they did
not measure relevant clinical outcomes. 85,86 To date, there is no good-quality
evidence to suggest that cranberry juice or its products is effective for the
treatment of UTI in any specific population at risk for UTI.84
8.2. There is evidence to recommend acupuncture for prevention of

recurrent UTI among women when antibiotic prophylaxis is
contraindicated.
Two small RCTs evaluated the role of acupuncture compared with sham
acupuncture or no treatment in the prophylaxis of recurrent UTIs. During a 6-month
period, both studies demonstrated that acupuncture could play a significant role in
preventing recurrent UTIs.87,88 However, both studies had different acupoints. The
main acupoints were Ren-3, Ub-23, and Ub-28 on the lower abdomen or back, and
K-3, Sp-6, Sp-9, Liv-2 or Liv-3 on the lower extremities and on the lower abdomen
or back (CV-3 or CV-4 and BL-23 or BL-28) or on the lower extremities (KI-3, SP-
6, SP-9, ST-36, or LR-3.87 Acupuncture was done 20 minutes twice weekly for 4
weeks.
40
One RCT involving 67 women with history of recurrent UTI randomized to

either acupuncture treatment, sham acupuncture treatment, or no treatment showed
that 85% of the acupuncture group were free of lower UTI during the 6-month
observation period, compared with 58% of the sham group (P=0.05) and 36% of the
control group (p=0.01).87
Another RCT of 94 women with 2 or more episodes of distal urinary symptoms
for the past 12 months showed that 73% of women in the acupuncture group were free
of UTIs during the 6-month observation period, compared with 52% of women in the
control group (p=0.08).88
8.3. There is no available evidence to recommend coconut juice in the

prevention or treatment of UTI.
Summary of evidence
We did not find any controlled or uncontrolled studies on coconut juice and its
role in the prevention or treatment of UTI.
8.4. There is insufficient evidence to recommend oral water hydration (2 to

2.5 liters/day) in the prevention or treatment of UTI.
Summary of evidence
A study on 28 pre-menopausal women who had at least two idiopathic UTIs
in the previous 6 months underwent assessment of urinary osmolality using a handheld
probe to determine any association of urine osmolality with bacteriuria.89 Results
showed that lower osmolality over the 4-month period was measured, and that there
was significantly fewer UTIs that developed during the study period (McNemar's
chi2=0.046).
8.5. There is insufficient evidence to recommend drinking more water and

voiding before and after intercourse to prevent UTI.
Summary of evidence
Benefits
We did not find any systematic review or randomized controlled trials.
However, a case control study comparing 229 women 18-30 years old with recurrent
UTI with 253 age-matched women found no significant difference in voiding habits
(infrequent, post-coital, pre-coital, delayed voiding) or fluid intake (<5 glasses of water
a day). There was also no difference in "wiping" (front to back) techniques. 17 An earlier
prospective study on risk factors for UTI in young women likewise showed that voiding
and drinking habits do not make a difference in the occurrence of UTIs. 90
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45. Beerepoot MA, ter Riet G, Nys S, et al. Cranberries vs antibiotics to prevent urinary tract infections:
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46. Terris MK, Issa MM, Tacker JR. Dietary supplementation with cranberry concentrate tablets may
increase the risk of nephrolithiasis. Urology. 2001 Jan;57(1):26-9.
47. Howell AB, Botto H, Combescure C, et al. Dosage effect on uropathogenic Escherichia coli anti-
adhesion activity in urine following consumption of cranberry powder standardized for
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14;10:94.
48. Beerepoot MA, ter Riet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a
randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012 May
14;172(9):704-12.
49. Stapleton AE, Au-Yeung M, Hooton TM, et al. Randomized, placebo-controlled phase 2 trial of a
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50. Barrons R, Tassone D. Use of Lactobacillus probiotics for bacterial genitourinary infections in women:
a review. Clin Ther. 2008 Mar;30(3):453-68.
51. Miller JL, Krieger JN. Urinary tract infections cranberry juice, underwear, and probiotics in the 21st
century. Urol Clin North Am. 2002 Aug;29(3):695-9.
52. Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens for preventing recurrent urinary tract
infection in postmenopausal women. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005131.
53. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent
urinary tract infections. N Engl J Med 1993; 329:753-6
54. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing
vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet
Gynecol. 1999 May;180(5):1072-9.
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55. Raz R, Colodner R, Rohana Y, et al. Effectiveness of estriol-containing vaginal pessaries and
nitrofurantoin macrocrystal therapy in the prevention of recurrent urinary tract infection in
postmenopausal women. Clin Infect Dis. 2003 Jun 1;36(11):1362-8.
56. Xu R, Wu Y, Hu Y. [Prevention and treatment of recurrent urinary system infection with estrogen
cream in postmenopausal women]. Zhonghua Fu Chan Ke Za Zhi. 2001 Sep;36(9):531-3.
57. Brown JS, Vittinghoff E, Kanaya AM, et al. Urinary tract infections in postmenopausal women: effect
of hormone therapy and risk factors. Obstet Gynecol. 2001 Dec;98(6):1045-52.
58. Cardozo L, Benness C, Abbott D. Low-dose oestrogen prophylaxis for recurrent urinary tract
infections in elderly women. Br J Obstet Gynecol 1998; 105: 403-7.
59. Kirkengen AL, Andersen P, Gjersøe E, Johannessen GR, Johnsen N, Bodd E. Oestriol in the
prophylactic treatment of recurrent urinary tract infections in postmenopausal women. Scand J Prim
Health Care. 1992 Jun;10(2):139-42.
60. Ouslander JG, Greendale GA, Uman G, Lee C, Paul W, Schnelle J.Effects of oral estrogen and
progestin on the lower urinary tract among female nursing home residents. J Am Geriatr Soc. 2001
Jun;49(6):803-7.
61. Huber M, Krauter K, Winkelmann G, Bauer HW, Rahlfs VW, Lauener PA, Blessmann GS, Bessler
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bacterial extract OM-89. Int J Immunopharmacol. 2000 Dec;22(12):1103-11.
62. Bauer HW, Rahlfs VW, Lauener PA, Blebmann GS. Prevention of recurrent urinary tract infections
with immuno-active E.coli fractions: a meta-analysis of five placebo-controlled double-blind studies.
Int J Antimicrob Agents 2002; 19:451-6.
63. Naber KG, Cho YH, Matsumoto T, Schaeffer AJ. Immunoactive prophylaxis of recurrent urinary tract
infections: a meta-analysis. Int J Antimicrob Agents. 2009 Feb;33(2):111-9. Epub 2008 Oct 28.
64. Frey C, Obolensky W, Wyss H. Behandlung von rezidivierenden Harnwegsinfektionen: Wirksameit
eines oral verabreichten. Imunbiotherapeutikums. Urol Int 1986; 41: 444-6.
65. Tammen H. Immunobiotherapy with Uro-Vaxom in recurrent urinary tract infection. The German
Urinary Tract Infection Study Group. Br J Urol. 1990 Jan;65(1):6-9.
66. Schulman CC, Corbusier A, Michiels H, Taenzer HJ. Oral immunotherapy of recurrent urinary tract
infections: a double-blind placebo-controlled multicenter study. J Urol. 1993 Sep;150(3):917-21.
67. Magasi P, Pánovics J, Illés A, Nagy M. Uro-Vaxom and the management of recurrent urinary tract
infection in adults: a randomized multicenter double-blind trial. Eur Urol. 1994;26(2):137-40.
68. Bauer HW, Alloussi S, Egger G, Blümlein HM, Cozma G, Schulman CC; Multicenter UTI Study Group.
A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients
with recurrent urinary tract infections. Eur Urol. 2005 Apr;47(4):542-8; discussion 548. Epub 2005 Jan
21.
69. Pisani E, Palla R, Bono AV. Double-blind randomised clinical study of OM-8930 versus placebo in
patients suffering from recurrent urinary tract infections [quoted by Chiavaroli C, Moore A. An
hypothesis to link the opposing immunological effects induced by the bacterial lysate OM-89 in urinary
tract infection and rheumatoid arthritis. BioDrugs 2006; 20:141–9]. Geneva, Switzerland: OM
PHARMA; 1992.
70. Guibert J, Humbert G, Meyrier A, Jardin A, Vallancien G, Piccoli S, Delavault P. [Antibioprevention of
recurrent cystitis. A randomized double-blind comparative trial of 2 dosages of pefloxacin]. Presse
Med. 1995 Jan 28;24(4):213-6.
71. Zhong YH, Fang Y, Zhou JZ, Tang Y, Gong SM, Ding XQ. Effectiveness and safety of patient initiated
single-dose versus continuous low-dose antibiotic prophylaxis for recurrent urinary tract infections in
postmenopausal women: a randomized controlled study. J Int Med Res. 2011;39(6):2335-43.
72. Seppänen J. Cinoxacin vs trimethoprim--safety and efficacy in the prophylaxis of uncomplicated
urinary tract infections. Drugs Exp Clin Res. 1988;14(10):669-71.
73. Nunez U, Solis 2. Macrocrystalline nitrofurantoin versus norfloxacin as treatment and prophylaxis in
uncomplicated recurrent urinary tract infection. Curr Ther Res. 1990;48:234-245.
74. Brumfitt W, Smith GW, Hamilton-Miller JM, Gargan RA. A clinical comparison between Macrodantin
and trimethoprim for prophylaxis in women with recurrent urinary infections. stamJ Antimicrob
Chemother. 1985 Jul;16(1):111-20.
75. Stamey TA. Prophylactic efficacy of nitrofurantoin macrocrystals and trimethoprim- sulfamethoxazole
in urinary infections: Biologic effects on the vaginal and rectal flora. N Engl J Med 1977; 296:780-3
76. Brumfitt W, Cooper J, Hamilton-Miller JM. Prevention of recurrent urinary infections in women: a
comparative trial between nitrofurantoin and methenamine hippurate. J Urol. 1981 Jul;126(1):71-4.
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77. Alexiou Z, Mouktaroudi M, Koratzanis G, et al. The significance of compliance for the success of
antimicrobial prophylaxis in recurrent lower urinary tract infections: the Greek experience. Int J
Antimicrob Agents. 2007 Jul;30(1):40-3.
78. Brumfitt W. Comparative study of cephradine and amoxicillin-clavulanate in the treatment of recurrent
urinary tract infections. Antimicrob Agents Chemother 1990; 34:1803-05
79. Cox CE. A comparison of the safety and efficacy of lomefloxacin and ciprofloxacin in the treatment of
complicated or recurrent urinary tract infections. Am J Med 1992; Suppl n4A:83S-86S
80. Wong ES. Management of recurrent urinary tract infections with patients-administered single-dose
therapy. Ann Intern Med 1985; 102:302-7
81. Schaeffer AJ, Stuppy BA. Efficacy and safety of self-start therapy in women with recurrent urinary
tract infections. J Urol. 1999 Jan;161(1):207-11.
82. Gupta K, Hooton TM, Roberts PL, et al. Patient-initiated treatment of uncomplicated recurrent urinary
tract infections in young women. Ann Intern Med 2001; 135: 9–16.
83. Johnson JR. Appropriateness of fluoroquinolones for therapy of urinary tract infection. Arch Intern
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84. Jepson, R. Cranberries for treating urinary tract infections. Cochrane Database of Systematic Rev
2010;(9).
85. DuGan CR, Cardaciootto PS. Reduction of ammonial urinary odors by the sustained feeding of
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86. Nahata MC, Cummins B A, McLeod DC. Effect of urinary acidifiers on formaldehyde concentration
and efficacy with methenamine therapy. Eur J Clin Pharmacol 1982;22(3):281–4.
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tract infection in adult women. Scand J Prim Health Care. 1998 Mar;16(1):37-9.
88. Alraek T, Soedal LI, Fagerheim SU, Digranes A, Baerheim A. Acupuncture treatment in the prevention
of uncomplicated recurrent lower urinary tract infections in adult women. Am J Public Health. 2002
Oct;92(10):1609-11.
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of recurrent idiopathic urinary tract infections in pre-menopausal women. Br J Urol. 1995 Jul;76(1):90-
3.
90. Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary
tract infection in young women. N Engl J Med. 1996 Aug 15;335(7):468-74.
91. Eells SJ, Bharadwa K, McKinnell JA, Miller LG. Recurrent urinary tract infections among women:
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infection. Clin Infect Dis 2014; 58 (2): 161-3.
45
Complicated UTI: General considerations
COMPLICATED URINARY TRACT INFECTIONS: GENERAL CONSIDERATIONS
Summary of Recommendations
1. When is complicated urinary tract infection suspected or diagnosed?
Complicated UTI (cUTI) is significant bacteriuria plus clinical symptoms,

which occurs in the setting of (1) functional or anatomic abnormalities of the
urinary tract or kidneys, or (2) the presence of an underlying disease that
interferes with host defense mechanisms, or (3) any condition that increases the
risk of acquiring [persistent] infection and/or treatment failure (See Table 5). The
cut-off for significant bacteriuria in complicated UTI has been set at 100,000
CFU/mL. However, in certain clinical situations, such as in catheterized patients,
low-level bacteriuria or counts < 100,000 CFU/mL maybe significant.
2. In patients with suspected complicated UTI, what diagnostic tests should be

done to assist the physician in managing the infection effectively?
2.1 A urine sample for gram stain, and culture and sensitivity testing must
always be obtained before the initiation of any treatment.
2.2 Additional ancillary diagnostic tests will depend on the nature of the
complicated UTI (see sections below). Imaging of the urinary tract is
warranted whenever anatomic or structural abnormalities are suspected
as contributing to a UTI. Such cases would include (a) pyelonephritis
that is not responding to usual treatment, (b) severe pyelonephritis in
certain high risk groups (e.g. DM), and (c) recurrent UTI in a man.
2.3 CT-scan is generally preferred over KUB ultrasound as it can better

identify and localize the presence of urinary tract abnormalities or
multiple lesions such as abscesses; however, the imaging modality to
be used may depend on local availability.
3. Do patients with complicated UTI need to be hospitalized?

3.1 The following patients with complicated UTI require hospitalization:
Patients with marked debility and signs of sepsis,
Patients in whom there is uncertainty in diagnosis,
Patients in whom there is concern about adherence to treatment, or,
Patients who are unable to maintain oral hydration or take oral
medications
3.2 Patients with mild to moderate illness (symptoms of fever and lower or
upper UTI without urosepsis, circulatory failure and/or organ
46
dysfunction or failure), and who do not fall under the above categories
may be treated on an outpatient basis.
4. What antibiotics are recommended for empiric therapy of complicated UTI?
4.1 For mild to moderate illness, oral fluoroquinolones or

amoxicillin/clavulanic acid may be used if there are no risk factors for
infection with antibiotic resistant organisms (such as ESBL producing-
organisms or P. aeruginosa, refer to Table 3) and if the resistance rates
to these antibiotics are < 20%. Due to the varying antibiotic sensitivity
patterns of the most common uropathogens, it is recommended that
local antibiotic sensitivity patterns be considered in the choice of
empiric antibiotics for this set of patients.
4.2 For severely ill patients, broad-spectrum parenteral antibiotics (see Table
3) should be used, choice of which would depend on the following:
The expected pathogens,
Results of the urine gram stain,
The current susceptibility patterns of microorganisms in the area,
and,
Risk factors for the acquisition of drug-resistant organism (Table
9)
4.3 Fluoroquinolones are not recommended as empiric antibiotics for

severely-ill patients due to the high rates of resistance locally.
4.4 Any underlying abnormalities or risk factors should be managed

accordingly.
5. How long should antibiotics be given in complicated UTI?
5.1 In general, at least 7-14 days of therapy is recommended. Treatment

duration may be extended depending on the clinical situation.
5.2 Antibiotics are modified according to the results of the urine culture and
sensitivity tests. Patients started with parenteral regimen may be switched
to oral therapy upon clinical improvement.
5.3 When an oral regimen is not available or if continuation of an

intravenously-administered antibiotic is necessary, outpatient
parenteral antibiotic therapy (OPAT) can be an option.
47
5.4 Criteria for OPAT include:

An indication for parenteral antibiotic therapy (i.e. presence of an
infection that warrants antibiotic use) in the absence of an oral or
alternate routes of delivery
No other clinical indication for hospitalization
Consent of the patient and/or caregiver to participate (including an
understanding of the benefits, risks, and economic considerations
involved)
Outpatient environment safe and adequate to support care (including
logistic concerns, rapid and reliable communications between the OPAT
team)
6. After the completion of antibiotics, what tests or procedures are

recommended to reduce the risk of recurrence of complicated UTI?
6.1 Urine culture should be repeated one to two weeks after completion of
antibiotics.
6.2 If significant bacteriuria persists post-treatment, consider referral to

specialists (infectious diseases, nephrology, urology, etc.) to identify and
correct any underlying problem (anatomical, functional, or metabolic) that
predisposes the patient to complicated UTI.
48
DISCUSSION
1. When is complicated urinary tract infection suspected or diagnosed?
Complicated UTI (cUTI) is significant bacteriuria plus clinical symptoms,

which occurs in the setting of (1) functional or anatomic abnormalities of the
urinary tract or kidneys, or (2) the presence of an underlying disease that
interferes with host defense mechanisms, or (3) any condition that increases the
risk of acquiring [persistent] infection and/or treatment failure (See Table 1). The
cut-off for significant bacteriuria in complicated UTI has been set at 100,000
CFU/mL. However, in certain clinical situations, such as in catheterized patients,
low-level bacteriuria or counts < 100,000 CFU/mL maybe significant.
Summary of evidence
Complicated UTIs (cUTIs) are a heterogeneous group of syndromes with
varying underlying pathogenic mechanisms that would warrant diagnostic and/or
therapeutic approaches that go beyond and are unique from those recommended for
uncomplicated UTIs. The heterogeneity, poor characterization, or lack of stratification
of complicating factors of the population included in various complicated UTI clinical
studies make it difficult to give uniform recommendations in its diagnosis and
management.1 At best, complicated UTI (cUTI) can be defined as significant bacteriuria,
which occurs in the setting of (1) functional or anatomic abnormalities of the urinary
tract or kidneys, (2) in the presence of an underlying disease that interferes with host
defense mechanisms, or (3) in the presence of any condition that increases the risk of
acquiring or persistence of infection and/or treatment failure (see Table 6). The cut-off
for significant bacteriuria in complicated UTI has been set at 100,000 cfu/ml. 2 However,
in certain clinical situations, such as in catheterized patients, low-level bacteriuria or
counts <100,000 cfu/ml may be significant.3
Complicated UTI can present as severe obstructive acute pyelonephritis

which may progress to urosepsis or as catheter-associated post-operative UTI, which
might resolve spontaneously with catheter removal. It may present with the usual
symptoms of dysuria, urgency, frequency, flank pain, costovertebral angle tenderness,
suprapubic pain, and fever, or with no symptoms at all. 4 It is important to note that the
presence of these symptoms, especially lower urinary tract symptoms, does not equate
with the presence of an infection. Other urological disorders such as benign prostatic
hyperplasia (BPH) or surgical manipulations of the urogenital tract such as transurethral
resection of the prostate (TURP) can also present with lower urinary tract symptoms.4
Patients with hormonal, metabolic, and immunologic deficiencies are more prone to
infection by various pathways. Usually, all these patients have pathogens that are more
difficult to eradicate.5 To date, there is little evidence clarifying the epidemiology of
complicated UTI. Population-based studies that clearly describe the burden of illness
of complicated UTI are lacking.6
Structural and functional abnormalities that impede urine outflow and cause urinary
stasis
Structural and anatomic abnormalities of the urinary tract that interfere with
the normal storage and flow of urine are among the most consistent elements
associated with a complicated UTI.7 This group of cUTIs include intrinsic and extrinsic
49
disorders of the kidney and renal infundibulum/pelvis (congenital abnormalities, calculi,

neoplasms, aberrant vessels, strictures, inflammatory bowel disease, retroperitoneal
hematoma/fibrosis), intrinsic or extrinsic abnormalities of the ureter (including calculi,
tumours, vesico-ureteral reflux, radiation inflammatory sequelae, retroperitoneal
fibrosis), pathology of the bladder and/or bladder neck (benign prostatic hyperplasia,
prostate or bladder cancer, bladder neck contraction, vesical calculi), neurogenic
bladder dysfunction, as well as disease of the urethra (e.g. polyps, structure, valves.
These conditions increase the likelihood of infection, with a tendency to be more
chronic, unless abnormalities are corrected. In the subset of cUTI patients with urinary
stones, for example, the more problematic Pseudomonas spp. and other urease-
producting bacteria, such as Proteus spp., seem to be more commonly involved.8
Table 6. Conditions that define complicated UTI

Presence of structural abnormalities causing urinary stasis and obstruction of the
genitourinary tract
Obstructive uropathy due to carcinoma, bladder outlet obstruction, calculus,
or cystocoele
Urethral or ureteric strictures, tumors, calculi and other urologic anatomic
abnormalities
Polycystic kidney disease
Functional abnormalities that affect normal urine outflow
Incomplete emptying of the bladder with >100 ml retained urine post-
voiding
Vesico-ureteral reflux
Neurogenic bladder, spina bifida, multiple sclerosis
Conditions that interfere with host defense mechanisms
Azotemia due to intrinsic renal disease
Diabetes mellitus
Immunosuppressive conditions – e.g. febrile neutropenia,
myeloproliferative disorders, chemotherapy
Iatrogenic conditions
Presence of an indwelling urinary catheter or intermittent catheterization,
stents
Peri- or post-operative UTI
Surgically created abnormalities
Pathogen-related complicating factors
UTI caused by unusual pathogens (M. tuberculosis, Candida spp.)
UTI caused by antibiotic-resistant or multi-drug resistant organisms
(MDROs)
Others
UTI in males except in young males presenting exclusively with lower UTI
symptoms
Chemical or radiation injuries of the uroepithelium
Urosepsis or severe pyelonephritis
50
Conditions that interfere with host defense mechanisms

While immunosuppression is a common risk factor for this group of
complicated UTI patients, there are many other mechanisms that contribute to their
susceptibility to severe infection and complications. In uremia, there is a physiologic
loss of several urinary defence mechanisms such as the loss of the antibacterial
properties of normal urine, due to urea or low pH and high osmolality. 4
Neutropenic patients (PMNs < 100/mm3) require special attention because
they may not manifest with the usual symptoms of UTI like dysuria, frequency, and
urgency. Pyuria may also be absent. In an early series by Sickles (1975) and cited by
Korzeniowski (1991), the incidence of UTI was associated with the severity of
neutropenia, increasing from 13% with PMNs > 1000/mm3 to 56% with PMNs <
100/mm3.9
Diabetes mellitus has been identified as an independent risk factor for the
occurrence of nosocomial UTI.10 Morbidity that occurs with diabetics who develop UTI
explains why these patients are included in the complicated UTI category.11 A separate
section is also dedicated for cUTI among diabetics.
Catheter-associated urinary tract infection (CA-UTI)

Some groups of complicated UTI, such as those with catheter-associated UTI,
are better studied. CA-UTI is one of the most common healthcare-associated infections
worldwide.12-14 This is the result of the widespread use of indwelling urinary foley
catheters, which in most cases have been described to be unnecessary. 13 As much as
five million patients are estimated to use these indwelling urinary catheters every year. 15
CA-UTI can account for as much as 40% of all nosocomial infection. 15 The
recent report of the International Nosocomial Infection Control Consortium (INICC)
(2012) which was based on a prospective surveillance study of a cohort of 3,877
patients hospitalized in 10 Pediatric Intensive Care Units during 27,345 bed days in 10
cities of six developing countries (Colombia, El Salvador, India, Mexico, Philippines,
and Turkey), noted a CA-UTI rate of 5.9 per 1000 urinary catheter- days.16
The incidence of CA-UTI in the Philippines has been studied in some
institutions. In a prospective cohort study done at a 1500-bed tertiary government
hospital in Manila in 1998, the incidence of catheter-related UTI was 51.4% (110 out of
214 catheterized patients), 91% of which were acquired within seven days of
catheterization.17 An earlier study in the same institution reported a 24.7% incidence
(44 out of 178 catheterized patients) over a three month period. 18 Range of duration of
catheterization, however, was shorter at 2 to 12 days compared to 2 to 44 days in the
more recent study. Another local study conducted in a tertiary private hospital reported
a relatively lower one-month prevalence of 13.6% (29 out of 212 catheterized patients)
with a mean duration of catheterization of 12 days. 19 Interestingly, a recent local quality
improvement study done at a tertiary government hospital in Manila noted zero
incidence of CA-UTI during a two-month observation period among catheterized
patients admitted to the general medical wards. 20
A separate section has been dedicated for the recommendations on the
diagnosis and management of CA-UTI. Additionally, the 2009 IDSA guidelines on CA-
UTI entitled, “Diagnosis, Prevention and Treatment of Catheter-associated Urinary
Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the
Infectious Diseases Society of America” has included an excellent discussion on the
51
epidemiology and pathogenesis of CA-UTI and the reader is encouraged to use this
material as reference.13
Renal transplant
Infections in the population of renal transplant patients have received much
interest in the field of research. It is now known that UTI is the most common infection
that occurs post-transplant, with the incidence ranging from 30-95%.21-26 Through the
years, there is a trend towards a gradual decline in the incidence of infection due to the
refinements in the post-operative care of transplant patients.24
UTI in post-transplant patients is associated with severe morbidity due to
sepsis. The highest rates of UTI occur during the first seven days following transplant
and consists mainly of CA-UTI. In the Philippines, the National Kidney and Transplant
Institute (NKTI) has the largest experience in kidney transplantation with 1,019 kidney
transplants performed in 1,008 patients over a ten-year period from 1983-1994. A one-
year prospective study in this institution by in 1997 followed the course of 513 patients
post-transplant and noted that UTI and pneumonia were the most frequently
encountered bacterial infections in these patients. 27 Refer to the section on cUTI among
post-renal transplant patients for more details.
HIV/AIDS
UTI in patients with HIV/AIDS was previously included in the category of
complicated UTI because of the higher risk for bacteriuria related to the degree of
immunosuppression, especially among patients with AIDS (CD4 count <200 cells/mL. 28-
32
However, most of these bacteriurias are asymptomatic and transient; whether or not
these bacteriurias predispose to the occurrence of a subsequent UTI in this set of
patients needs further investigation. 28,29,33 In a prospective cohort of 871 HIV-
seropositive and 439 HIV-seronegative women, it was found out that within the 4280
person-years of follow-up, HIV infection was not associated with the development of
UTI.34 More studies are needed to characterize the effect of HIV on the risk of acquiring
UTI [35]. It is also interesting to note at this point that in at least two studies, concomitant
intake of TMP-SMX for Pneumocystis pneumonia (PCP) prophylaxis did not
significantly influence the rate of bacteriuria. One reason for this is that the most
common urinary pathogens already have high rates of resistance to TMP-SMX.29,32
While those with advanced HIV infection and UTI are at higher risk for unusual
or atypical pathogens (e.g. cytomegalovirus, adenovirus, Toxoplasma, Pneumocystis
jiroveci, Blastomyces dermatidis, Mycobacterium tuberculosis), the most common
causes of UTI in these patients are not different from those that cause UTIs in HIV-
seronegative individuals.28,30,36 The management of UTI in patients with HIV is similar
to the management of UTI in seronegative patients. For this reason, the committee has
decided to remove HIV/AIDS in the list of conditions under complicated UTI. Patients
with HIV/AIDS who do not respond to usual treatment should be evaluated for atypical
or unusual pathogens listed previously, and should be referred to an appropriate
specialist.
2. In patients with suspected complicated UTI, what diagnostic tests

should be done to assist the physician in managing the infection
effectively?
52
2.1 A urine sample for gram stain, and culture and sensitivity testing must
always be obtained before the initiation of any treatment.
2.2 Additional ancillary diagnostic tests will depend on the nature of the
complicated UTI (see sections below). Imaging of the urinary tract is
warranted whenever anatomic or structural abnormalities are suspected
as contributing to a UTI. Such cases would include (a) pyelonephritis
that is not responding to usual treatment, (b) severe pyelonephritis in
certain high risk groups (e.g. DM), and (c) recurrent UTI in a man.
2.3 CT-scan is generally preferred over KUB ultrasound as it can better

identify and localize the presence of urinary tract abnormalities or
multiple lesions such as abscesses; however, the imaging modality to
be used may depend on local availability.
Summary of evidence
In cases where it is possible, antimicrobial therapy should be delayed until the
results of culture and sensitivity studies are released so that therapy would be targeted
towards the identified pathogen. In cases where empiric treatment is started, re-
assessment of the choice of antibiotic should be done as soon as culture results
become available (usually within 48-72 hours).37
The importance of obtaining pre-treatment urine cultures in patients with
complicated UTIs cannot be overemphasized for several reasons. 1,38-41 First, there is a
wide range of organisms that can cause complicated UTI. Table 7 lists the most
commonly reported pathogens in complicated UTI by several foreign and local studies.
While E. coli remains to be the most commonly reported pathogen in cUTIs, the
significance of more problematic organisms such as Pseudomonas spp., other urease-
producing bacteria such as Proteus spp., staphylococci and enterococci have been
recognized.42
The second reason why obtaining pre-treatment cultures is very important is
because culture and sensitivity results will confirm that the infecting organism is
susceptible to the empiric antibiotic started given the increasing rates of antibiotic
resistance.1 Finally, pre-treatment culture and sensitivity results will allow shifting of the
initial empiric antibiotic to one with a narrower spectrum of coverage which may be
cheaper and minimize selection of more resistant pathogens. Culture-guided antibiotic
treatment is especially important among patients in whom prolonged antibiotic therapy
is warranted or recurrent infections are more likely (e.g. complicated UTI patients for
whom the complicating factor(s) is/are not readily reversible).
3. Do patients with complicated UTI need to be hospitalized?
3.1 The following patients with complicated UTI require hospitalization:

Patients with marked debility and signs of sepsis,
Patients in whom there is uncertainty in diagnosis,
Patients in whom there is concern about adherence to treatment, or,
53
Patients who are unable to maintain oral hydration or take oral

medications
Table 7. Pathogens in Complicated UTI

Type of Complicated Pathogens Reference
UTI
Complicated UTI in Escherichia coli, Klebsiella [43-47]
Filipino patients (NKTI, pneumonia, Enterobacter cloacae,
PGH, MMC, CSMC, Pseudomonas aeruginosa, Proteus
DMC) mirabilis
Catheter-associated UTI
Short-term (<1 week)
Escherichia coli [48]
Pseudomonas aeruginosa
Long-term (>1 week)
Escherichia coli, Klebsiella sp., [49, 50]
Enterobacter sp., Proteus mirabilis
Usually polymicrobial
E. coli, Pseudomonas aeruginosa,
Proteus mirabilis, Providencia stuartii,
Morganella morgagnii, Citrobacter,
Enterococcus, Candida species
Catheter-associated UTI Escherichia coli, Klebsiella, [17, 18]
in Filipino Patients Pseudomonas aeruginosa,
Acinetobacter, Candida sp.
Anatomic abnormalities Escherichia coli, Klebsiella [51]
pneumoniae (37%), Pseudomonas
aeruginosa, Proteus mirabilis
UTI in diabetics Escherichia coli, Klebsiella [11, 52,
pneumoniae, Proteus mirabilis, 53]
Enterobacter, Enterococcus,
Pseudomonas aeruginosa, Candida,
Staphylococcus aureus
Diabetics with indwelling Escherichia coli, Enterococcus, [52]
bladder catheter Pseudomonas aeruginosa
Renal transplant Escherichia coli (29-61%), Proteus [27, 54-58]
recipients mirabilis and Klebsiella pneumoniae
(30%), Gram-positive cocci (20%),
Enterobacter, Enterococci, Serratia,
Acinetobacter, Citrobacter,
Pseudomonas aeruginosa, Candida
Neutropenic patients Gram negative bacilli, Pseudomonas [9]
aeruginosa, Staphylococcus aureus,
Candida
54
3.2 Patients with mild to moderate illness (symptoms of fever and lower or
upper UTI without urosepsis, circulatory failure and/or organ
dysfunction or failure), and who do not fall under the above categories
may be treated on an outpatient basis.
Summary of evidence
The decision on the site-of-care and subsequent choice of empiric antibiotics is in
part dependent on the clinical status of the patient. No disease severity classification
system has been formulated and evaluated for complicated UTIs. Not surprisingly, there
are no clinical trials that stratified patient outcomes by degree of illness and site of
treatment. Clinical decision-making rests upon the status of the patient and the
presence of risk factors for severe and/or persistent infection. Mild to moderate illness
can range from an asymptomatic patient with complicating factors (as listed in Table 1)
to the presence of fever and upper/lower UTI symptoms. Severe illness, on the other
hand, can be characterized by urosepsis, circulatory failure, organ dysfunction and/or
failure.4
4. What antibiotics are recommended for empiric therapy of complicated UTI?

4.1 For mild to moderate illness, oral fluoroquinolones or
amoxicillin/clavulanic acid may be used if there are no risk factors for
infection with antibiotic resistant organisms (such as ESBL producing-
organisms or P. aeruginosa, refer to Table 3) and if the resistance rates
to these antibiotics are < 20%. Due to the varying antibiotic sensitivity
patterns of the most common uropathogens, it is recommended that
local antibiotic sensitivity patterns be considered in the choice of
empiric antibiotics for this set of patients.
4.2 For severely ill patients, broad-spectrum parenteral antibiotics (see Table
3) should be used, choice of which would depend on the following:
a) The expected pathogens,
b) Results of the urine gram stain,
c) The current susceptibility patterns of microorganisms in the
area, and,
d) Risk factors for drug-resistant organism (Table 9)
4.3 Fluoroquinolones are not recommended as empiric antibiotics for

severely-ill patients due to the high rates of resistance locally.
4.4 Any underlying abnormalities or risk factors should be managed

accordingly.
55
Summary of evidence
The proper selection of empirical treatment for cUTI requires 3 things: (1)
knowledge of the possible infectious agents based on the complicating factors present,
(2) knowledge on the local antibiotic resistance patterns, and (3) an assessment of the
severity of the underlying urological abnormality. The wide variety of pathogens that are
implicated in complicated UTI tend to be more resistant to the common antibiotics used
in clinical practice as described by several recent reviews of earlier studies. 1,37,59,60 This
is attributed to the increased probability of complicated UTI patients for repeated
antimicrobial exposure or healthcare-associated acquisition of these pathogens (e.g.
frequent hospital visits for underlying medical condition, urological interventions). 37 The
variety of conditions under complicated UTI and the limitations of the clinical trials in
these populations are also very important factors that contribute to the difficulty in
coming up with generalizations on specific antibiotic regimens. 61 Drugs of choice for
empiric therapy of complicated UTI have not been well established. The earlier
published comparative drug trials on complicated UTI were poorly designed or the
definition of bacteriologic cure was not eradication of the initial pathogen.
One prospective, randomized, single-blind multicenter study involving 133
patients suspected of having cUTI showed that lomefloxacin (a fluoroquinolone) is
superior over trimethoprim-sulfamethoxazole (TMP-SMX or cotrimoxazole) in terms of
bacteriologic cure and clinical cure of symptomatic complicated UTI. 62 This study and
the increasing rates of resistance to TMP-SMX in three local antibiotic susceptibility
reports favour against the use of TMP-SMX in cUTI.61 Similar with uncomplicated UTIs,
the very high resistance rates to ampicillin and amoxicillin limit the use of these
antibiotics to cases with culture-proven, susceptible isolates of enterococci or Group B
streptococci.61-63
In 2005, Nicolle and the Association of Medical Microbiology and Infectious
Diseases Canada Guidelines Committee reviewed at least 28 previously published
comparative clinical trials on complicated UTI. The committee has validated the
previously identified limitations of clinical trials on complicated UTI in terms of
heterogeneity in study subjects, size of treatment effect, lack of blinding or allocation
concealment, and variability of follow-up duration. Moreover, concerns on the
usefulness in the choice of empiric antibiotics have been raised for those studies that
excluded infections with drug-resistant organisms.37 These available studies have
shown that the different classes of fluoroquinolones are equally effective for the
treatment of complicated UTI (except for sparfloxacin and moxifloxacin). For example,
a multicenter, prospective, double-blind, double-dummy randomized study compared
ciprofloxacin 250 mg BID to ofloxacin 200 mg BID given for seven days in the treatment
of 427 women with complicated lower UTI.64 No significant differences in efficacy rates
among patients who received ciprofloxacin and ofloxacin were observed: 77.1% and
76.1% had sterile cultures five to nine days after therapy respectively. Clinical cure five
to nine days post-therapy was achieved in 97.2% of both groups and a month later in
87.7% and 87.3%, respectively. Adverse events were mild and similar in both groups.
Once daily administration of 1000mg of extended release ciprofloxacin has also been
found to be at least as safe and effective as the 500 mg BID regimen in two clinical
trials.65,66 Levofloxacin 750 mg once daily for 5 days has been shown to be as effective
as ciprofloxacin 400 mg (intravenous) or 500 mg (oral) twice daily for 10 days in the
treatment of adults with cUTI and acute pyelonephritis, including patients with
concurrent bacteremia.67 On the other hand, sparfloxacin (not available locally) and the
56
newer moxifloxacin achieve relatively lower concentrations in urine and are not
indicated for the treatment of UTI.68,69
Based on the studies enumerated above, the 2004 guideline recommended
the use of oral fluoroquinolones for the treatment of mild to moderate complicated UTIs.
However, there have been increasing reports of fluoroquinolone resistance among
uropathogens in the past few years attributed to the spread of ESBL-producing
bacteria.61 It has been observed that when an isolate becomes ESBL-producing,
particularly E. coli, fluoroquinolone resistance follows. Surveillance reports on the
antimicrobial susceptibility of Gram-negative pathogens in the Asia-Pacific region have
shown that among ESBL-producing E. coli, most antibiotic agents showed decreased
in vitro activity compared with the ESBL-negative counterparts (Chen et al., 2011). In
the study done at a private tertiary hospital in Pasig City, resistance to the
fluoroquinolones was 100% for ESBL-producing E.coli.44 In addition, fluoroquinolones
have been shown to have detrimental effects ecologically. They have a tendency to
select for resistant strains of P. aeruginosa, P. mirabilis, Providencia spp., and Serratia
spp., and to induce cross-resistance to structurally unrelated antimicrobials.70
Considering the issue of increasing resistance together with the collateral
damage that fluoroquinolones may cause (e.g. in tuberculosis, ESBL-production,
selection of resistant strains stated above), it is therefore advised to use
fluoroquinolones with caution and only after careful assessment of the patient’s risk
factors for acquiring drug-resistant organisms such as prior antibiotic use (third
generation cephalosporins, fluoroquinolones) in the past three to six months, recent
hospitalization or urological instrumentation (indwelling bladder catheter included) have
been considered.
The Philippine Antimicrobial Resistance Surveillance Program (ARSP)
performs laboratory surveillance to monitor antibiotic resistance from selected isolates
from various sentinel sites in the country. The latest 2013 ARSP Data Summary Report
showed that E. coli from inpatient urine specimens was least resistant to oral
nitrofurantoin (%R 6%, n=1,622) followed by amoxicillin/clavulanic acid (co-amoxiclav)
(%R 23%, n=1,974) (see Table 3).71 Among the parenteral agents, ertapenem (%R 2%,
n=1,059) had the lowest resistance rates followed by piperacillin-tazobactam and
amikacin with resistance rates both at 6%. From 2012 to 2013, only ceftriaxone had a
significant increase in resistance rate from 31% to 36% (p=0.006); the resistance rates
of the other antibiotics did not differ significantly. These figures were pooled from data
submitted by 22 sites throughout the entire Philippines; however, variability still exists
from one institution to another. The ARSP 2013 Data Summary report thus
recommends that treatment recommendation be based on local prevailing antibiotic
sensitivity patterns. In a study done in a tertiary private hospital done in Metro Manila
involving adult patients admitted for cUTI, similar trends in antibiotic resistance patterns
were observed.44 Resistance rates to the intravenous ertapenem and amikacin, and to
the oral nitrofurantoin remain low. Note the high resistance rates to ciprofloxacin and
levofloxacin. Given these data, the carbapenems and amikacin are good options for
empiric treatment for patients in whom intravenous antibiotics are indicated. Oral
antibiotic options would include nitrofurantoin and co-amoxiclav (Table 8). Note,
however, that nitrofurantoin have only been approved for use in uncomplicated cystitis.
The development of resistance and the lack of clinical studies favour against the use of
this drug for severe or complicated UTIs. 61
57
Table 8. Percent Resistance of Urinary E. coli (inpatient urine specimens)

Antimicrobial Agent ARSP ARSP cUTI study
2013* 2015** 2013+
%R %R ESBL-producing
(n, %R)
Amikacin 6% 4.2% 0
Ampicillin 85% 83.9% 48 (100%)
Ceftazidime - - 44 (91.7%)
Ceftriaxone 36% 40.4% 47 (97.9%)++
Cefuroxime axetil 40% 38.1% 48 (100%)
Ciprofloxacin 46% 43.4% -
Co-amoxiclav 23% 27.1% 38 (79.2)
Ertapenem 2% 5.7% 0
Gentamicin - - 24 (50.0%)
Imipenem - - 0
Levofloxacin - - 43 (93.8)
Meropenem - - 0
Nitrofurantoin 6% 6.5% 12 (34.3%)
Piperacillin-tazobactam 6% 10.7 16 (45.7%)
Tigecycline - - 5 (15.2%)
TMP-SMX 69% 67.9% 40 (83.3%)
%R (resistance rate) = percentage of isolates resistant
*Antimicrobial Resistance Surveillance Program (ARSP), 2013 report
**Antimicrobial Resistance Surveillance Program(ARSP), 2015 report
+From a study on complicated UTI in a tertiary private hospital in Metro Manila
++Intravenous ceftriaxone
Another important consideration in choosing the appropriate empiric antibiotic

regimen for complicated UTIs is the presence of risk factor(s) in acquiring antibiotic-
resistant organisms (see Table 9). The global phenomenon of rising antimicrobial
resistance among Enterobacteriaceae has likewise been observed in the region and in
the Philippines. This problem includes ESBL (extended spectrum beta-lactamase) or
KPC (K. pneumoniae carbapenemase) production, fluoroquinolone and TMP-SMX
resistance and even multidrug-resistance [61]. ESBL-rate in the Asia-Pacific region is
reported at 28.2%.72 Several studies have already identified risk factors associated with
the development of cUTI with antibiotic-resistant organisms and are summarized in
Table 9. The role of staphylococci or enterococci have been found to be insignificant
unless there are risk factors such as the presence of stones or foreign bodies. 4
Locally, a cohort study done at a tertiary hospital in Manila in 2007 reported
an ESBL rate of 13% out of 300 consecutive Enterobacteriaceae isolates from adult
patients.94 Another cohort study done in a private tertiary hospital (n=161 patients,
33.5% of hospital-acquired UTI) in Metro Manila from September 2011 to August 2012
looked into the prevalence of ESBL-producing organisms among patients with
complicated UTI. They reported ESBL-rates of 29%. Multivariate analysis of risk factors
done identified structural or anatomic abnormality and recurrent urinary tract surgery or
instrumentation (OR 2.81, CI 1.26 to 6.29, p=0.012 and OR 18.16, CI 2.08 to 158.35.
p=0.009) as significant risk factors for development of complicated UTI with an ESBL-
producing organism. Further analysis of the E. coli subgroup in this study (n=96)
58
showed that structural or anatomic abnormality and fluoroquinolone intake in the

preceding three months (OR 6.41, CI 1.95 to 21.03, p=0.002 and OR 5.43, CI 1.26 to
23.33. p=0.023) are significant risk factors for development of complicated UTI with an
ESBL-producing organism.44 In a similar study conducted in a government tertiary
hospital, on the other hand, reported a higher ESBL rate of 37% (n=177) with
mechanical ventilation (OR R 2.48, 95% CI 1.21-5.13, p=0.014) as the only significant
factor associated with the development of ESBL infection on multivariate analysis. 86
Table 9. Risk factors for the acquisition of antibiotic-resistant organisms.

ESBL-producing organisms Reference
Prolonged stay in a hospital or healthcare facility [73, 74]
Recent use of antibiotics* (fluoroquinolones, cephalosporins, [75-83]
B-lactams)
Recent hospitalization (past 3 months) [78, 84]
Recent travel to ESBL-highly endemic areas (Asia, The Middle [77, 81]
East or Africa) in the past 6 weeks
Presence of Diabetes mellitus and/or other co-morbidities [73, 74, 77,
(e.g. neutropenia) 80]
Urinary catheterization, surgery or instrumentation and use of [44, 73, 79,
other invasive devices 80, 83]
Recent episode of UTI, recurrent UTI [73, 74, 82,
85]
Structural or anatomical abnormality of the genitourinary tract, [44, 82]
including prostatic disease
Mechanical ventilation [86, 87]
Pseudomonas (including multi-drug resistant Pseudomonas)
Use of antibiotics in the past 2 months* (ciprofloxacin, BLICs) [88-91]
Recent episode of UTI [91, 92]
Previous urinary tract surgery, catheterization [91-93]
Underlying urinary tract pathology (e.g. pathological VCUG [89, 92, 93]
results)
Recent stay in another healthcare unit/facility [90]
*Includes antibiotic use for prophylaxis.
For severely ill patients and for those in whom antibiotic resistance, such as
ESBL-production, is a concern, intravenous broad spectrum antibiotics listed in Table
10 are the next options.44,59,61,95 Most uropathogens, including the ESBL-producing
organisms, are sensitive to amikacin. 44,71 Anti-pseudomonal carbapenems are
recommended for suspected Pseudomonas aeruginosa or Acinetobacter sp infections.
Otherwise, the Group 1 carbapenem, ertapenem, may be used.59 At least two studies
of sound methodologic quality have demonstrated the effectiveness of ertapenem as
an empiric antibiotic for complicated UTI. 96,97 Wells et al. (2004) compared the efficacy
and safety of parenteral ertapenem for the treatment of complicated UTI in adults with
ceftriaxone in two prospective, double-blind, randomized studies with similar design. 97
Ertapenem and ceftriaxone were administered at a dose of 1 g once daily. In both
studies, patients could be switched to an oral agent after ≥3 days of parenteral study
therapy. The duration of treatment was 10 to 14 days. At the primary efficacy end point
59
five to nine days after treatment, 229 (89.4%) patients in the ertapenem group and 204
(91.1%) patients in the ceftriaxone group had a favorable microbiological response
(95% CI, –7.4 to 4.0), which indicates comparable outcomes in both treatment groups.
In this combined analysis, ertapenem was found to be an effective therapy for the
treatment of complicated UTIs in adults with moderate-to-severe disease. The more
recent report by Park et al. (2012) was a prospective, multicenter, double-blinded,
randomized study involving 271 patients with acute pyelonephritis or complicated UTI. 96
The efficacy and safety of ertapenem 1 g once daily were compared with ceftriaxone 2
g once daily, for the treatment of adults with acute pyelonephritis and complicated UTI.
Results showed that ertapenem was equally effective and safe as ceftriaxone in
achieving bacteriologic response at five to nine days after treatment with similar
frequency and severity of reported adverse events.
Finally, together with initiation of antibiotics, any underlying abnormality or
complicating factor should be addressed. Adequate glucose control should be achieved
for diabetic patients. The need for an indwelling should be reassessed and any
indwelling device should be removed soon as it is deemed to be not indicated anymore.
Urologic abnormalities should be corrected whenever possible. Proper infection control
practices should be exercised to minimize and prevent further infections.
5. How long should antibiotics be given in complicated UTI?
5.1 In general, at least 7-14 days of therapy is recommended. Treatment

duration may be extended depending on the clinical situation.
5.2 Antibiotics are modified according to the results of the urine culture and
sensitivity tests. Patients started with parenteral regimen may be switched
to oral therapy upon clinical improvement.
Table 10. Antibiotics that may be used as empiric therapy for complicated UTI
Oral Regimen
Ciprofloxacin 500 -750 mg BID or 1000 mg extended release tablet OD x 7-14d*
Norfloxacin 400 mg BID x 7-14d*
Ofloxacin 200 mg BID x 10-14d*
Levofloxacin 500-750 mg OD x 7-14d*
Amoxicillin/clavulanate 500 mg/125mg TID or 875 mg/125 mg BID x 7-14d
Parenteral Regimen
Amikacin 15mg/kg q24h+
Doripenem 500 mg q8h
Ertapenem 1 gm. q24h
Gentamicin 3-5 mg/kg/day q24h+
Imipenem-cilastin 250-500 mg q6-8h
Meropenem 1g q8h
Piperacillin-Tazobactam 2.25-4.5 gms q6-8h
*Determine if patient has risk factors for drug-resistance prior to use.
+Monitor kidney function especially for patients with impaired renal function at baseline
60
5.3 When an oral regimen is not available or if continuation of an

intravenously-administered antibiotic is necessary, outpatient parenteral
antibiotic therapy (OPAT) can be an option.
5.4 Criteria for OPAT include:

An indication for parenteral antibiotic therapy (i.e. presence of an
infection that warrants antibiotic use) in the absence of an oral or
alternate routes of delivery
o No other clinical indication for hospitalization
o Consent of the patient and/or caregiver to participate (including an
understanding of the benefits, risks, and economic considerations
involved)
o Outpatient environment safe and adequate to support care
(including logistic concerns, rapid and reliable communications
between the OPAT team)
Summary of evidence
A randomized, double-blind, placebo-controlled trial (Dow et al., 2004)
compared 3-day (n=30) and 14-day (n=30) regimens of ciprofloxacin 250 mg BID for
the treatment of acute UTI in patients with spinal cord injury. The most common
infecting organisms were Klebsiella, Enterococcus, and E. coli. On intention-to-treat
analysis, the three-day regimen was associated with a higher rate of microbiological
relapse at six weeks after initiation of therapy (37% vs. 7%; RR 2.09, 95% CI 1.38 to
3.18). Short-term (19-23 days after enrolment) and long-term (45-51 days) clinical cure
did not differ significantly between the 3-day and 14-day regimens (short term: 63%
vs.53%; RR 1.23, 95% CI 0.72 to 2.11; long- term: 37% vs. 40%; RR 0.93, 95% CI 0.55
to 1.58). Likewise, microbiological cure (30% vs. 47%; RR 0.69, 95% CI 0.39 to 1.23)
and treatment failure (13% vs. 37%; RR0.46, 95% CI 0.19 to 1.11) did not differ
significantly between the two regimens. There were more ciprofloxacin-resistant
organisms isolated in the 14-day treatment regimen. The advantage of this 14-day
regimen would have been more profound had there been similar number of
ciprofloxacin-resistant isolates (e.g. Enterococci) in both arms. Reasons proposed for
the higher rate of microbiological relapse in the three-day regimen include: (1) patients
may have had occult infections of the upper urinary tract (which would warrant longer
treatment duration), and (2) impaired vesical clearance of bacteriuria because of
localized trauma, frequent instrumentation or incomplete bladder emptying. 98,99
An open non-comparative clinical trial on sequential therapy with IV
levofloxacin for three days followed by oral levofloxacin to complete 14 days for
complicated UTI in three tertiary government hospitals in the Philippines showed 89%
cure rate at day 14 on efficacy analysis and 72% on intention-to-treat analysis.100
No data is available providing evidence on the advantage of 7-, 10- or 14-day
antibiotic treatment regimen in terms of likelihood of cure or the incidence of adverse
effects with prolonged antibiotic use.
61
Outpatient parenteral antibiotic therapy (OPAT)

Outpatient parenteral antibiotic therapy (OPAT) has been practiced in
developed countries such as the U.S. since the 1970s. 101 However, this concept has
not gained as much popularity in the Philippines. OPAT is generally used to refer to the
provision of parenteral antimicrobial therapy in at least 2 doses on different days without
intervening hospitalization according to the 2004 IDSA Guidelines on Outpatient
Parenteral Antibiotic Therapy.102 There are no studies that looked solely into the
outcomes of OPAT when used in cUTI but numerous studies have included cUTI as
one of the indications for OPAT. These studies, although most are retrospective, that
support the effectiveness and safety of this strategy. 102-104 In a recent survey conducted
among adult infectious disease physicians in North America, 81% of the respondents
indicated that they have treated at least 1 patient with OPAT per month on the average.
Complications were rare and included intravenous line occlusion or clotting,
nephrotoxicity and rash. This study found out that there remains a wide variation in the
practice of OPAT.105
While there are variations in this strategy, OPAT requires at least 3 things: (1)
an indication for treatment (i.e. presence of an infection that warrants antibiotic usage),
(2) hospitalization is not needed to control the infection, and (3) alternate routes of drug
delivery are not feasible or appropriate. 102 The primary goal of OPAT is to allow patients
to complete treatment safely and effectively on an outpatient basis and avoid the
inconveniences, complications, and expense of hospitali-zation. It is important that
patient safety is not compromised for comfort or financial reasons in the conduct of
OPAT. There are four models of OPAT based on where or who delivers the antibiotic:
(1) administration in an infusion center, (2) delivery via visiting home services (e.g.
physician, nurse), (3) self-administration or administration by a caregiver, and (4)
delivery in a nursing home or long term care facility. It is important that the individual
setting be assessed first and ensure that OPAT, through any of the four models
described, is feasible. Table 11 summarizes the criteria for patient eligibility prior to
OPAT and the corresponding issues that need to be addressed first.
Once a decision to push through with OPAT is made, it is important that the
key elements be addressed to ensure that the patient receives comprehensive and
quality care without compromising safety. Table 12 summarizes these key elements
based on recommendation by IDSA in 2004.102 Transition of care is very important prior
to patients discharge. An OPAT plan should be documented in the discharge summary.
Clear follow-up instructions and requests for necessary laboratory tests should be
issued. For patients who will self-administer the antibiotics, vascular access education
and sterile technique should have been ensured. 106
6. After the completion of antibiotics, what tests or procedures are

recommended to reduce the risk of recurrence of complicated UTI?
6.1 Urine culture should be repeated one to two weeks after completion of
antibiotics.
6.2 If significant bacteriuria persists post-treatment, consider referral to

specialists (infectious diseases, nephrology, urology, etc.) to identify
62
and correct any underlying problem (anatomical, functional, or

metabolic) that predisposes the patient to complicated UTI.
Table 11. Criteria for Outpatient Parenteral Antibiotic Therapy (OPAT)

Criteria Issues to be addresses
1. Is parenteral Is there an infection that warrants parenteral
antimicrobial therapy antimicrobial therapy administration?
indicated? Is there an oral form or any other alternatives routes?
2. No other clinical Are there no clinical contraindications to discharge
indication for the patient from hospital?
hospitalization
3. Consent of the patient Does the patient and/or caregiver understand the
and/or caregiver to benefits, risks, and economic considerations
participate involved?
Does informed consent need to be documented?
Is the patient willing to comply with a follow-up plan?
4. Is the home or Are the patient and/or caregiver willing to participate
outpatient environment and able to safely, effectively, and reliably deliver
capable, safe and parenteral antimicrobial therapy?
adequate to support Do the patient’s medical care needs exceed
care? Is OPAT feasible resources available at the proposed site of care?
and doable? Are the logistics for OPAT available?
Are mechanisms for rapid and reliable
communications about problems and for monitoring
of therapy in place between members of the OPAT
team?
References: Tice et al (2004) [102] and Muldoon et al (2014) [106]
Summary of evidence
Infection is likely to recur if the underlying abnormalities that predisposed the
patient to complicated UTI are not corrected. Thus, it is necessary to check urine
cultures one to two weeks after completion of antibiotics to document bacteriologic cure
(Stamm & Hooton, 1993). There are, however, no convincing data indicating that clinical
benefit is gained by knowing that asymptomatic bacteriuria is present after treatment
for asymptomatic UTI and that it is beneficial to perform routine post-treatment urine
cultures for asymptomatic patients. On the other hand, persistence or recurrence of
symptoms after treatment of a symptomatic UTI episode warrants evaluation and
retreatment.
In most cases of complicated UTI, further intervention is necessary to
eradicate the infection in addition to the administration of antibiotics. For instance, in
the management of UTI with struvite stones, definitive treatment like extracorporeal
shock wave lithotripsy and/or percutaneous nephrolithotomy or lithotripsy may be
required in most patients. Bacteria live within the stone and persist contributing to stone
growth. Patients who fail to undergo stone removal usually have progressive renal
deterioration.107 Further work-up to identify anatomic abnormalities may include the
following: plain abdominal and kidney-ureter-bladder radiographs, renal ultrasound,
intravenous pyelogram, CT scans, and MRI. Work-up for immunodeficient state may be
done when considered.
63
Table 12. Key elements required for an outpatient parenteral antimicrobial therapy
(OPAT) program.
1. Health care team
A. An infectious diseases specialist or physician knowledgeable about
infectious diseases and the use of antimicrobials in OPAT
B. Primary care or referring physicians available to participate in care
C. Nurse expert in intravenous therapy, access devices, and OPAT
D. Pharmacist knowledgeable about OPAT
E. Case manager and billing staff knowledgeable about therapeutic issues and
third party reimbursements
F. Access to other health care professionals, including a physical therapist, a
dietitian, an occupational therapist, and a social worker
2. Communications
A. Physician, nurse, and pharmacist available 24 h per day
B. System in place for rapid communication between patient and team
members
C. Patient education information for common problems, side effects,
precautions, and contact lists
3. Outline of guidelines for follow-up of patients with laboratory testing and intervention as
needed
4. Written policies and procedures
A. Outline of responsibilities of team members
B. Patient intake information
C. Patient selection criteria
D. Patient education materials
5. Outcomes monitoring
A. Patient response
B. Complications of disease, treatment, or program
C. Patient satisfaction
Adapted from Muldoon, E.G., et al., Are We Ready for an Outpatient Parenteral Antimicrobial
Therapy Bundle? A Critical Appraisal of the Evidence. Clinical Infectious Diseases, 2013. 57(3): p.
419-424.
References
1. Brown, P.D. and J.D. Sobel, Advances in the understanding and treatment of complicated
urinary tract infections. European Urological Review, 2007(2): p. 51-53.
2. Rubin, R.H., et al., Evaluation of New Anti-Infective Drugs for the Treatment of Urinary Tract
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69
UTI in diabetics
SPECIFIC ISSUES OF CONCERN IN COMPLICATED URINARY TRACT INFECTION
UTI IN DIABETIC PATIENTS
1. How should UTI in diabetic patients be managed?
1.1 Diabetic patients require pre-treatment urine gram stain and culture and
a post-treatment urine culture. At least 7-14 days of oral or parenteral
antibiotics listed in Table 8 (Complicated UTI: General Considerations)
may be used.
1.2 Diabetic patients who present with signs of sepsis should be

hospitalized. Blood culture, in addition to urine culture, is indicated for
severely ill patients before starting therapy. Failure to respond to
empiric therapy within 48 to 72 hours warrants a plain abdominal
radiograph of the KUB, a renal ultrasound, or a CT-scan.
2. Should diabetic patients be screened and treated for asymptomatic

bacteriuria?
Screening and treatment for asymptomatic bacteriuria among diabetic

patients are not recommended because they do not reduce the occurrence
of subsequent infectious complications.
70
UTI in diabetics
DISCUSSION
1. How should UTI in diabetic patients be managed?

1.1 Diabetic patients require pre-treatment urine gram stain and culture and
a post-treatment urine culture. At least 7-14 days of oral or parenteral
antibiotics listed in Table 8 (Complicated UTI: General Considerations)
may be used.
1.2 Diabetic patients who present with signs of sepsis should be
hospitalized. Blood culture, in addition to urine culture, is indicated for
severely ill patients before starting therapy. Failure to respond to empiric
therapy within 48 to 72 hours warrants a plain abdominal radiograph of
the KUB, a renal ultrasound, or a CT-scan.
Summary of evidence
When UTIs occur in diabetics, they are often more serious and protracted.
Due to the immunocompromised state, they are at an increased risk for developing
ascending renal infection, pyelonephritis, papillary necrosis, renal carbuncle, renal
corticomedullary and perinephric abscesses, and emphysematous pyelonephritis. 1
Emphysematous pyelonephritis is a severe, necrotizing interstitial nephritis caused by
gas-forming organisms probably acquired via a hematogenous route. Factors that may
predispose diabetics to complicated infections include autonomic neuropathy leading
to poor bladder emptying and urinary stasis, microangiopathy, leukocyte dysfunction,
and frequent urinary tract instrumentation.2 In addition, diabetic nephrosclerosis and
renal disease make delivery of antimicrobials less efficacious. 3 In more recent studies,
there was an increased risk of acute pyelonephritis caused by Enterobacteriaceae from
the lower urogenital tract in patients with diabetes mellitus.1 Infection with Klebsiella is
common (25% compared with 12% in non-diabetics).1,4
Strong evidence is lacking but experts agree that because of the concern for
subsequent upper tract involvement, longer duration of antibiotic therapy is advocated
in diabetic patients even with just lower UTI.5,6 In addition, the increased risk for
recurrent tract disease among diabetics justify the need for pre- and post-treatment
urine cultures. Failure to respond to therapy within 48 to 72 hours requires serious
consideration for any of the severe complications of upper urinary tract infection
peculiar to diabetes. This includes any of the ff: emphysematous pyelonephritis,
emphysematous cystitis, renal papillary necrosis, acute focal or multifocal bacterial
nephritis, renal cortical abscess, renal corticomedullary abscess, and
xanthogranulomatous pyelonephritis. Emphysematous pyelonephritis, although rare,
carries a poor prognosis if not detected early and treated with medical management
alone. Mortality is up to 60% without surgical intervention. 7 A plain abdominal film of the
kidney, ureter, and bladder can detect up to 85% of cases. A screening ultrasound
should be considered early to rule out obstructive uropathy and detect parenchymal
lesions. If there is a high degree of clinical suspicion despite a negative ultrasound, CT
scanning should be pursued.8
A multicenter, prospective, double-blind, double-dummy randomized study of
427 women including 85 (20%) with DM, has shown that a seven-day regimen with
ciprofloxacin or with ofloxacin resulted in a cure rate of 90.1%and 87.2% respectively,
71
UTI in diabetics
five to nine days post-treatment. In the group of women with DM, the success rates
were comparable (87.1% and 85.3%).9 However, one should consider the increasing
rates of resistance to fluoroquinolones as previously discussed. Risk factors for drug-
resistance should be considered when contemplating the use of fluoroquinolones as
the empiric antibiotic option.
Local susceptibility patterns of the organism should guide choice of antibiotic
therapy. Oral or parenteral fluoroquinolones (for mild to moderate infections with no risk
for drug-resistance) or ertapenem are reasonable empiric choices. For seriously ill
patients, including patients infected with Pseudomonas spp., such agents as imipenem,
ticarcillin-clavulanate, and piperacillin-tazobactam may be considered.10 Patients
suspected of having staphylococcus infection should be started on vancomycin if there
are risk factors for developing such infections, such as presence of invasive devices,
residence or exposure to a health-care facility, living in crowded places and men having
sex with men. Shift to oxacillin or nafcillin once isolates are found to be susceptible to
such antibiotics.
No randomized trials are available comparing the optimal duration and choice
of antibiotics among diabetics.
Gestational diabetes mellitus is not associated with increased risk of UTI or
with maternal and perinatal morbidity because of infection. Microbiologic evidence of
UTI was studied in 447 pregnant women with (n=149) and without (n=298) gestational
diabetes mellitus after mid-pregnancy. No significant difference in asymptomatic
bacteriuria, symptomatic infection and recurrent bacteriuria later in pregnancy were
seen among those with and without gestational DM. E. coli was the most common
pathogen.11
2. Should diabetic patients be screened and treated for asymptomatic

bacteriuria?
Screening and treatment for asymptomatic bacteriuria among diabetic
patients are not recommended because they do not reduce the occurrence of
subsequent infectious complications.
Summary of Evidence (also refer to Chapter on Asymptomatic bacteriuria)

Asymptomatic bacteriuria is common among diabetic women (8-14%).12 On
the other hand, the incidence of bacteriuria does not appear to be increased among
diabetic men.13 A case-control study of 228 women with diabetes and 146 women
without diabetes showed that impaired metabolic control of diabetes, as revealed by
higher glycated hemoglobin levels, significantly increased the risk for developing ASB
(p <0.05).14
One meta-analysis that evaluated whether asymptomatic bacteriuria is more
common in patients with diabetes than among control subjects was recently conducted.
The review included 22 studies and reported that indeed, asymptomatic bacteriuria
occurs more frequently among diabetic patients and in all subsets of diabetic patients
such as females (OR 2.6, 95% CI 1.6-4.1), males (OR 3.7, 95% CI 1.3-10.2), and in
children and adolescents (OR 5.4, 95% CI 2.7-11).15 Moreover, the study concluded
that diabetic patients with asymptomatic bacteriuria had more albuminuria and
symptomatic UTIs. This increased prevalence of ASB in diabetics may be largely
attributable to autonomic neuropathy leading to impaired bladder voiding. 16
72
UTI in diabetics
Considering the potential risk to developing subsequent (more complicated)

symptomatic UTIs among diabetics, a randomized, placebo-controlled, double-blinded
trial that enrolled 105 diabetic women assigned to receive placebo or an antimicrobial
agent was conducted.17 Study results showed that the time to a first symptomatic
episode (p=0.67 by the log-rank test), the rates of any symptomatic UTI (RR 1.19; 95%
CI 0.28 to 1.81), pyelonephritis (RR 2.13; 95% CI 0.81 to 5.62), and hospitalization for
UTI (RR 1.93; 95% CI 0.47 to 7.89) were similar in the placebo group and the
antimicrobial-therapy group. The study concluded that screening and treatment for
asymptomatic bacteriuria in diabetic women did not reduce complications. The
Infectious Diseases Society of America (IDSA) likewise recommended against the
screening or treatment of asymptomatic bacteriuria in this population in its 2005
Guidelines for the Diagnosis and Treatment of Asymptomatic bacteriuria.1,17
References:
1. Grabe, M., et al. Guidelines on urological infections. 2014 [cited 2014 September 3]; Available from:
http://www.uroweb.org/gls/pdf/19%20Urological%20infections_LR.pdf.
2. Lee, D.-G., et al., Acute Pyelonephritis: Clinical Characteristics and the Role of the Surgical
Treatment. J Korean Med Sci, 2009. 24(2): p. 296-301.
3. Hoepelman, A.I.M., R. Meiland, and S.E. Geerlings, Pathogenesis and management of bacterial
urinary tract infections in adult patients with diabetes mellitus. International Journal of Antimicrobial
Agents, 2003. 22, Supplement 2(0): p. 35-43.
4. Ramakrishnan, K. and D.C. Scheid, Diagnosis and management of acute pyelonephritis in adults. Am
Fam Physician, 2005 Mar 1. 71(5): p. 933-42.
5. Patterson, J.E. and V.T. Andriole, Bacterial urinary tract infections in diabetes. Infect Dis Clin North
Am, 1997 Sep. 11(3): p. 735-50.
6. Stamm, W.E. and T.M. Hooton, Management of Urinary Tract Infections in Adults. New England
Journal of Medicine, 1993. 329(18): p. 1328-1334.
7. Evanoff, G.V., et al., Spectrum of gas within the kidney: Emphysematous pyelonephritis and
emphysematous pyelitis. The American Journal of Medicine, 1987. 83(1): p. 149-154.
8. Meiland, R., S.E. Geerlings, and A.I.M. Hoepelman, Management of bacterial urinary tract infections
in adult patients with diabetes mellitus. Drugs, 2002. 62(13): p. 1859-68.
9. Raz, R., et al., Ciprofloxacin 250 mg twice daily versus ofloxacin 200 mg twice daily in the treatment
of complicated urinary tract infections in women. Eur J Clin Microbiol Infect Dis, 2000 May. 19(5): p.
327-31.
10. Stapleton, A., Urinary tract infections in patients with diabetes. The American Journal of Medicine,
2002. 113(1, Supplement 1): p. 80-84.
11. Rizk, D.E., N. Mustafa, and L. Thomas, The prevalence of urinary tract infections in patients with
gestational diabetes mellitus. Int Urogynecol J Pelvic Floor Dysfunct, 2001. 12(5): p. 317-21;
discussion 321-2.
12. Zhanel, G.G., et al., Prevalence of Asymptomatic Bacteriuria and Associated Host Factors in Women
with Diabetes Mellitus. Clinical Infectious Diseases, 1995. 21(2): p. 316-322.
13. Zhanel, G.G., G.K.M. Harding, and L.E. Nicolle, Asymptomatic bacteriuria in patients with diabetes
mellitus. Rev Infect Dis, 1991 Jan-Feb. 13(1): p. 150-4.
14. Bonadio, M., et al., Asymptomatic Bacteriuria in Women with Diabetes: Influence of Metabolic Control.
Clinical Infectious Diseases, 2004. 38(6): p. e41-e45.
15. Renko, M., et al., Meta-Analysis of the Significance of Asymptomatic Bacteriuria in Diabetes. Diabetes
Care, 2011. 34(1): p. 230-235.
16. Harding, G.K.M., et al., Antimicrobial Treatment in Diabetic Women with Asymptomatic Bacteriuria.
New England Journal of Medicine, 2002. 347(20): p. 1576-1583.
17. Nicolle, L.E., et al., Infectious Diseases Society of America Guidelines for the Diagnosis and
Treatment of Asymptomatic Bacteriuria in Adults. Clinical Infectious Diseases, 2005. 40(5): p. 643-
654.
73
UTI in renal transplant patients
SPECIFIC ISSUES OF CONCERN IN COMPLICATED URINARY TRACT

INFECTION
CATHETER-ASSOCIATED URINARY TRACT INFECTION (UTI)
1. When is catheter-associated urinary tract infection (CA-UTI) suspected
or diagnosed?
1.1 UTI in patients with an indwelling urethral or suprapubic catheter or
in those undergoing intermittent catheterization is termed as CA-
UTI. CA-UTI is diagnosed when:
Fever and/or other signs or symptoms compatible with UTI are
present with no other identified source of infection;
At least 103 colony forming units (cfu)/mL of at least 1 bacterial
species are present in a single catheter urine specimen or in a
midstream voided urine specimen;
In a patient with an indwelling urethral, suprapubic or condom
catheter, or which has been removed within the previous 48
hours.
1.2 There is no sufficient evidence to define the quantitative cut-off for
CA-UTI among men with condom catheters.
2. Should patients with indwelling urethral, indwelling suprapubic, or

intermittent catheterization be screened and treated for asymptomatic
bacteriuria?
2.1 Screening and treatment of catheter-associated asymptomatic
bacteriuria (CA-ASB) are not routinely recommended.
2.2 Screening and treatment of CA-ASB are recommended only for
pregnant patients and those who will undergo urologic procedures.
2.3 Data is insufficient to make any recommendations regarding
screening and treatment of CA-ASB among post-solid organ
transplant and neutropenic patients.
3. In patients with suspected CA-UTI, what diagnostic tests should be done

to assist the physician in managing the infection effectively?
3.1 Similar with the general recommendations in complicated UTI (cUTI),

it is necessary to obtain urine gram stain and cultures BEFORE
starting empiric antibiotic coverage for CA-UTI.
3.2 In catheterized patients, pyuria alone is NOT diagnostic of CA-UTI and

should not be interpreted as an absolute indication for initiating
empiric antibiotics.
74

3.3 The presence or absence of odorous or cloudy urine alone in
catheterized patients is also not an indication for antibiotic treatment.
4. How should urine for culture and sensitivity studies be collected from
patients with suspected CA-UTI?
4.1 For patients in whom catheterization is still indicated, the urine
specimen should be obtained from the freshly placed catheter prior to
the initiation of antimicrobial therapy. Urine sample should be
aspirated from the catheter port, or if not present, by puncturing at the
distal end of the catheter with a sterile needle and syringe after
disinfecting the area WITHOUT disconnecting the junction of the
catheter and drainage tube.
4.2 For individuals whose catheters can be or have been recently removed
and requires no further catheterization, a mid-stream, clean catch
urine should be obtained. Urine samples for culture should not be
obtained from collection bags.
4.3 Urine specimens for culture should be processed as soon as possible,
preferably within one hour of obtaining the specimen. If this is not
possible, the urine specimen should be refrigerated. Refrigerated
specimens should be processed within 24 hours.
5. What are the antibiotics that can be used for the treatment of CA-UTI?
5.1 Since CA-UTI is often a healthcare-associated infection, the choice of
empiric antibiotics to be used will be institution-specific depending on the
local susceptibility patterns and the severity of patient’s illness. Refer to
Table 14.
5.2 Seven days of antimicrobial treatment is recommended for patients who
have prompt resolution of symptoms and 10 to 14 days of antimicrobial
treatment for patients whose response is delayed.
6. What is the approach to the presence of the indwelling urinary catheter once
the diagnosis of CA-UTI is made?
6.1 Whenever possible, the indwelling catheter should be removed to help
eradicate the bacteriuria.
6.2 For patients in whom indwelling bladder catheterization is necessary,
long-term indwelling catheters should be replaced with new catheters
before initiating antimicrobial therapy for symptomatic UTI.
75
7. What strategies are effective in reducing the risk of CA-UTI?
Strategies for reducing the risk of CA-UTI

Strategy Strength of Level of
Recommendation Evidence
Use indwelling catheters only when Strong Low
necessary
Use aseptic technique including Strong Low to
appropriate hand hygiene and sterile Moderate
gloves
Allow only trained health personnel to Weak Low
insert Foley catheters
Properly secure catheters after insertion Weak Low
to prevent
movement and urethral traction
Maintain a closed sterile drainage Strong Moderate
system.
Maintain good hygiene at the catheter- Strong Moderate
urethral interface.
Maintain unobstructed urine flow Strong Moderate
Remove catheters when no longer Strong High
needed.
Do not change indwelling catheters or Weak Low
drainage bags at fixed intervals.
It is recommended that appropriate strategies for the prevention of CA-UTI (listed

in the Table above) be included and implemented in an institution-specific,
multimodal, quality improvement bundle. Periodic assessment of compliance
with these bundles, once instituted, is likewise recommended.
8. Is condom catheter a reasonable alternative to indwelling

catheterization in the prevention of CA-UTI?
Condom catheterization is an alternative to indwelling catheter
for male patients in whom a urinary catheter is necessary provided post-
void residual urine is minimal and the patient has no cognitive
impairment.
9. Is intermittent catheterization a reasonable alternative to indwelling

catheterization to prevent CA-UTI?
Intermittent catheterization can also be considered an
alternative to short term (strong recommendation, moderate quality of
evidence) or long-term (weak recommendation, moderate quality of
evidence) indwelling urinary catheterization with trained and dedicated
healthcare staff. Intermittent catheterization, however, requires more
manpower hours as well as the full cooperation of patients for frequent
repeated catheterization.
76
10. Is suprapubic catheterization an alternative to urethral catheterization?

Suprapubic catheterization may be an alternative to urethral
catheterization when there are excellent support mechanisms from the
surgical and caregiver staff.
11. What should NOT be done for patients with urinary catheters?
The following should NOT be done in an effort to reduce CA-
UTI because their use has not been shown to prevent the development
of subsequent bacteriuria or symptomatic UTI:

Use of antibiotic–coated catheters Strong High
Routine use of systemic prophylactic Strong Moderate
antibiotics at the time of insertion, during
and upon removal of indwelling urinary
catheters
Catheter or bladder irrigation with Strong High
antimicrobial agents
Routine addition of antibiotics or Strong High
antiseptics to drainage bags and antireflux
vents and valves
Daily meatal care Strong High
Changing of catheters and drainage bags Weak Low
at arbitrarily fixed intervals
12. How can unnecessary long-term catheterization be avoided?

Consider using alternative strategies for timely removal and
prevention of unnecessary long-term catheterization such as instituting
automatic stop orders, nurse-based or electronic physician reminder
systems or chart reminders.
Weak recommendation, Moderate quality of evidence
77
DISCUSSION
1. When is catheter-associated urinary tract infection (CA-UTI) suspected or
diagnosed?
1.1 UTI in patients with an indwelling urethral or suprapubic catheter or in
those undergoing intermittent catheterization is termed as CA-UTI. CA-
UTI is diagnosed when:
Fever and/or other signs or symptoms compatible with UTI are present with
no other identified source of infection;
At least 103 colony forming units (cfu)/mL of at least 1 bacterial species are
present in a single catheter urine specimen or in a midstream voided urine
specimen;
In a patient with an indwelling urethral, suprapubic or condom catheter, or
which has been removed within the previous 48 hours.
1.2 There is no sufficient evidence to define the quantitative cut-off for CA-
UTI among men with condom catheters.
Summary of Evidence
Since the last Philippine Clinical Practice Guidelines on UTI Update 2004, the
diagnostic criteria for CA-UTI has evolved and improved. The quantitative count of at
least 103 cfu/mL is a compromise between a sensitive level of detecting true bladder
bacteriuria in a catheterized patient and the capability of most microbiology laboratories
in quantifying growth on culture media. 1
The presence of symptoms and signs suggestive of UTI among catheterized
individuals is an essential component of the diagnosis. In patients with long-term
indwelling catheters due to spinal injury, the following are also considered symptoms of
possible CA-UTI: increased spasticity, autonomic dysreflexia, or sense of unease.
Among those whose catheters have been recently removed, dysuria, urgent or frequent
urination, or suprapubic pain or tenderness are signs and symptoms of a possible CA-
UTI.
Bacteremia is an important complication of CA-UTI. Bacteremia with the
urinary tract as the source occurs in 11% to 40% of nosocomial bacteremic episodes.
Patients with bacteremia may present with confusion, chills, fever, and hypotension. 2
On the other hand, the diagnosis of CA-UTI should not be based on symptomatology
alone. Not all lower urinary tract symptoms in catheterized patients should be attributed
to CA-UTI. Cohort studies of catheterized patients have shown that the usual symptoms
referable to the urinary tract such as fever, dysuria, frequent urination and urgency may
not be as reliable in diagnosing an infection when a catheter is in place.3-5 Patients with
neurogenic bladder or elderly patients may not be able to show any local symptoms. 1
The entire clinical context should always be considered together with assessment of
risk factors and microbiologic investigation.
Certain risk factors for CA-UTI have been identified by local and foreign
studies which may help the clinician in the difficult dilemma of deciding whether or not
to treat as CA-UTI. Table 13 below summarizes these risk factors.
78
2. Should patients with indwelling urethral, indwelling suprapubic, or

intermittent catheterization be screened and treated for asymptomatic
bacteriuria?
2.1 Screening and treatment of catheter-associated asymptomatic
bacteriuria (CA-ASB) are not routinely recommended.
2.2 Screening and treatment of CA-ASB are recommended only for

pregnant patients and those who will undergo urologic procedures.
2.3 Data is insufficient to make any recommendations regarding

screening and treatment of CA-ASB among post-solid organ
transplant and neutropenic patients.
Table 13. Risk factors for catheter-associated urinary tract infection, based on
prospective studies and use of multivariable statistical modelling.6
Factor Relative Risk
Prolonged catheterization >6 days 5.1 - 6.8
Female gender 2.5 - 3.7
Catheter insertion done outside the operating room 2.9 - 5.3
Urology Service 2.0 - 4.0
Other active site of infection 2.2 - 2.4
Diabetes 2.3 – 2.4
Malnutrition 2.4
Azotemia (creatinine > 2.0 mg/dL) 2.1 – 2.6
Ureteral stent 2.5
Monitoring of urine output 2.0
Drainage tube below bladder but above collection bag 1.9
Antibiotic usage 0.1 – 0.4
Summary of Evidence
The presence of bacteria is not infrequently seen in catheterized patients
without any complaints, signs, and symptoms suggestive of UTI. This situation is
regarded as CA-ASB, which is defined as the presence of significant bacteriuria in a
patient WITHOUT signs or symptoms referable to the urinary tract.1 Significant
bacteriuria in patients with indwelling urethral, indwelling suprapubic or intermittent
catheterization is the presence of at least 103 cfu/ml of at least 1 bacterial species in a
single catheter urine specimen. For male patients on condom catheter, the presence of
at least 105 cfu/ml of at least 1 bacterial species in a single catheter urine specimen
from a freshly applied condom catheter is considered significant.
Both foreign and local studies have confirmed the inevitability of the
occurrence of significant bacteriuria by the 30th day that the indwelling catheter remains
in place.7,8 The incidence of significant bacteriuria among catheterized patients with
initially absent or low-count bacteriuria ranged from 18% to 62% within 2 days from
catheterization.9 It has also been described that the bacteriuria in otherwise healthy or
asymptomatic catheterized patients will often resolve spontaneously with the removal
79
of the catheter.10 It is difficult to fully assess the natural history of CA-ASB because
patients with short-term indwelling catheters in acute care facilities often receive
antimicrobial therapy for indications other than UTI. However, available evidence
seems to point to the conclusion that CA-ASB does not present with an increased risk
of progression to UTI.5 A randomized control trial (RCT) of treatment with cephalexin
versus no treatment of asymptomatic bacteriuria in long-term catheterized patients
showed no benefit, and increased rates of antibiotic-resistant bacteria in the treated
group.11
In another RCT of treatment with trimethoprim-sulfamethoxazole
(cotrimoxazole) versus no treatment of persistent catheter-acquired bacteriuria 48
hours following catheter removal, 26% of women in the placebo group developed
symptoms within 14 days, while 36% had spontaneous resolution. 12 Furthermore, in the
non-treated group, bacteriuria resolved spontaneously in 74% of women younger than
65 years of age, and 4% of women over 65 years. Bacteriologic cure at 4 weeks was
89% in the treated group of women younger than 65 years and 62% of women over 65
years.
Finally, a non-comparative study of sequential antibiotic therapy in an elderly
population also showed that treatment of asymptomatic bacteriuria does not eliminate
bacteriuria and usually results in replacement with organisms resistant to the antibiotic
given.13 Therefore, CA-ASB need not be treated, and the catheter need not be removed
because: (1) the risk of complications is low; (2) treatment does not prevent bacteriuria
from recurring; and (3) treatment may lead to the emergence of antimicrobial-resistant
bacteria (and Clostridium difficile) that are more challenging to treat.
Special populations which may benefit from antibiotic treatment and thus
deserve screening and treatment of CA-ASB include pregnant women and those who
will undergo urologic procedures. This recommendation is similar to their non-
catheterized counterparts and based on a randomized controlled treatment trial in non-
catheterized pregnant women that showed that eradication of ASB reduces the risk for
pyelonephritis and adverse consequences in pregnancy (see also Chapter on
Asymptomatic Bacteriuria in Pregnancy). 14 The conclusion was extrapolated to the
catheterized pregnant women as no study had been done in this population. Similarly,
patients who will undergo invasive genitourinary procedures associated with mucosal
bleeding where high rates of post-procedure bacteremia and sepsis have been
previously documented belong to the special population where screening for bacteriuria
is recommended even if asymptomatic. Again no direct studies have been done on this
subset of patients.
Because data is insufficient to make any recommendations, screening for CA-
ASB in certain groups of immunocompromised patients (e.g. post-solid organ transplant
patients on immunosuppressive therapy and neutropenic patients) will depend on the
clinical situation. The decision will lie on the physician who should weigh the benefits of
screening and consequences of non-treatment against the negative effects, which
include suprainfections, unnecessary costs, collateral damage to microbial ecology and
subsequent antibiotic resistance leading to impaired effectiveness of current and future
antimicrobial agents.
3. In patients with suspected CA-UTI, what diagnostic tests should be done

to assist the physician in managing the infection effectively?
80
3.1 Similar with the general recommendations in complicated UTI (cUTI),

it is necessary to obtain urine gram stain and cultures BEFORE
starting empiric antibiotic coverage for CA-UTI.
3.2 In catheterized patients, pyuria alone is NOT diagnostic of CA-UTI
and should not be interpreted as an absolute indication for initiating
empiric antibiotics.
3.3 The presence or absence of odorous or cloudy urine alone in

catheterized patients is also not an indication for antibiotic
treatment.
Summary of evidence
Invariably, pyuria will develop for most catheterized patients due to the
inflammation and irritation of the genitourinary mucosa with the foreign body in place.
A prospective, cross-sectional study involving 761 newly catheterized patients reported
that pyuria only had a sensitivity of 37% for predicting CA-UTI.5 In addition, another
study that performed sequential quantitative urine cultures and urinalyses on 177 urine
specimens from 14 patients on long-term catheter use showed that there was pyuria
even during asymptomatic periods.15 During symptomatic infections, neither urinalyses
nor urine cultures displayed changes (e.g. increased number of pus cells, increased
colony counts) that may correlate with such events. Another prospective, cross-
sectional study among patients with neurogenic bladder requiring chronic
catheterization examined the relationship of pyuria with bacteriuria. The study
concluded that levels of pyuria did not distinguish patients with bacteriuria from those
without.16
Hence, pyuria alone is not diagnostic of CA-UTI and should not be interpreted as
an absolute indication for initiating empiric antibiotics. The absence of pyuria in a
symptomatic catheterized patient, on the other hand, makes the diagnosis of CA-UTI
unlikely.1 A properly collected urine specimen should be sent for urine cultures for the
diagnosis of CA-UTI (Refer to Complicated UTI General Guidelines for summary of
evidence).
4. How should urine for culture and sensitivity studies be collected from
patients with suspected CA-UTI?
4.1 For patients in whom catheterization is still indicated, the urine
specimen should be obtained from the freshly placed catheter prior
to the initiation of antimicrobial therapy. Urine sample should be
aspirated from the catheter port, or if not present, by puncturing at
the distal end of the catheter with a sterile needle and syringe after
disinfecting the area WITHOUT disconnecting the junction of the
catheter and drainage tube.
4.2 For individuals whose catheters can be or have been recently
removed and requires no further catheterization, a mid-stream,
81
clean catch urine should be obtained. Urine samples for culture

should not be obtained from collection bags.
4.3 Urine specimens for culture should be processed as soon as
possible, preferably within one hour of obtaining the specimen. If
this is not possible, the urine specimen should be refrigerated.
Refrigerated specimens should be processed within 24 hours.
Summary of Evidence
Organisms yielded from urine cultures should accurately reflect the actual
pathogen causing the infection. This will then be translated to accurate antimicrobial
sensitivity testing and appropriate antibiotic choice for the patient. One study compared
the qualitative and quantitative microbiology of paired urine samples from old urine
catheters and newly inserted ones. Despite having a high sensitivity, urine microbiology
of old catheters had poor specificity.17 The number of species and quantitative count of
bacteria isolated in urine collected through a catheter in place for several days is greater
than a simultaneous specimen collected through a freshly placed catheter. 18,19 Thus,
urine samples from newly-inserted catheters are the preferred specimens for pre-
treatment cultures among patients with CA-UTI.
For patients whose catheters have been recently placed, urine sample should
be aspirated from the catheter port, or if not present, by puncturing at the distal end of
the catheter with sterile needle and syringe after thorough disinfection. 1 A closed
system should always be maintained ensuring that the catheter and drainage tube are
not disconnected from one another. For CA-UTI developing in a patient in whom the
catheter has been in place for at least 2 weeks (and catheterization is still indicated), it
is recommended that the catheter be replaced and the urine specimen taken after the
new catheter has been inserted For individuals whose catheters can be or have been
recently removed and requires no further catheterization, a mid-stream, clean catch
urine should be obtained. Urine samples for culture should not be obtained from
collection bags.
5. What are the antibiotics that can be used for the treatment of CA-UTI?
5.1 Since CA-UTI is often a healthcare-associated infection, the choice
of empiric antibiotics to be used will be institution-specific depending
on the local susceptibility patterns and the severity of patient’s illness.
Refer to Table 14.
Seven days of antimicrobial treatment is recommended for patients who

have prompt resolution of symptoms and 10 to 14 days of antimicrobial
treatment for patients whose response is delayed.
Summary of Evidence
The rationale for recommending the listed drugs of CA-UTI are extensions
from that of cUTI in general. The choice of empiric antibiotic depends on the severity of
illness, the risk factors for drug-resistance and the local antimicrobial susceptibility
82
patterns, given that most CA-UTIs are healthcare associated.20 Kindly refer to the
summary of evidence in the General Guidelines in the Management of cUTI.
For CA-UTI, it is very important to assess the risk factors of patients for the
development of infections secondary to important nosocomial pathogens such as
Pseudomonas or drug-resistant microorganisms. In a case-control study of 58 patients
with infection from extended-spectrum beta-lactamase (ESBL)-producing organisms
(bloodstream, urinary tract, vascular catheter) and 116 control patients, multivariate
analysis showed that recent antibiotic treatment in another country with a high
prevalence of ESBL (OR 27.01; 95% CI 2.38, 1733.28; p=0.042), antibiotic therapy
within the past year (OR 2.88; 95% CI 1.13, 8.49; p=0.025) and mechanical ventilation
(OR 10.6; 95% CI 1.06, 579.10; p=0.042) are all associated with ESBL-producing
isolates.21 A similar study, which included patients with Klebsiella pneumoniae
bloodstream infections (n=147), reported that exposure to antibiotic therapy (OR 11.81;
95% CI 2.72, 51.08), prolonged hospitalization (OR 1.10; 95% CI 1.04, 1.16) and
advanced age (OR 1.14; 95% CI 1.08, 1.21) were the significant factors for the isolation
of ESBL-producing Klebsiella.22 A local cohort study of UTI patients reported that
structural or anatomic abnormality (OR 2.81, CI 1.26 to 6.29, p=0.012) and recent
urinary tract surgery or instrumentation (OR 18.16, CI 2.08 to 158.35. p=0.009) and as
significant risk factors for development of complicated UTI with an ESBL-producing
organism on multivariate analysis.23 The OR for fluoroquinolone intake in the preceding
three months was 2.56 (95% CI 0.96, 6.87) but did not reach statistical significance.
Risk factors for Pseudomonas infection include male patient, being
transferred from another intensive care unit (ICU); antibiotic already started at
admission; prolonged ICU stay or more than 10 days of hospital stay; ICU incidence of
Pseudmonas-infected patients; ICU with a high patient turnover; neurogenic bladder;
history of prostatic surgery; urinary tract procedures; a foreign body in the urinary tract;
and chronic corticosteroids use.24,25
In several published reviews, the recommended duration of treatment ranges
from 7 to 14 days.26,27 In the 2009 Infectious Disease Society of America (IDSA)
Guidelines on the Diagnosis, Prevention and Treatment of Catheter-associated Urinary
Tract Infection in Adults, the optimal treatment duration for CA-UTI appear to be
between 3 and 14 days.1 They have considered two studies involving catheterized
patients with neurogenic bladder and spinal cord injury. These studies compared a 3-
day course versus a longer course (10 days and 14 days) of antibiotics (either
ciprofloxacin or cotrimoxazole). One study showed that rates of cure, persistence, and
relapse were similar.28 On the other hand, the more recent study reported that
microbiological and symptomatic relapse were significantly greater among the patients
who received the 3-day course.29 These conflicting results and the fact that some of
these studies included only patients with mild illness (not the entire spectrum of CA-UTI
patients who tend to have more severe disease) and patients in whom the infecting
isolates recovered were sensitive to the empiric antibiotic (data is unavailable regarding
the effect of a three-day course of empiric antibiotic therapy when the pathogens
isolated are resistant to the empiric antibiotic started) are the reasons for the
recommended longer course of antibiotic treatment for CA-UTI.
83
Table 14. Antibiotics Options for the Treatment of CA-UTI

Antibiotic Recommended Dose Comments
and Duration
Amikacin (First line) 15 mg/kg q24h Be cautious in giving
aminoglycosides in patients with
renal insufficiency
Ertapenem 1g IV q24h1 For patients with no risk for
Pseudomonas or Enterococcus
Anti-Pseudomonal carbapenems For patients with risk for
Doripenem2 500 mg q8h Pseudomonas infection
Imipenem-cilastin3 500 mg q6h For ESBL-producing
Meropenem4 1 g q8h Enterobacteriaceae
Vancomycin 1g IV q 12 For suspected staphylococcal
infections5
Colistin (Colistimethate sodium) For multidrug-resistant
Colomycin6 31,250–62,500 IU/kg per Enterobacteriaceae, Klebsiella
day, divided in 2-4 equal pneumonia carbapenemase-
doses producing (KPC) bacteria, Multi-
(240-480 mg/kg/day) drug resistant (MDR)
Pseudomonas sp. or MDR
Coly-Mycin Double the dose of
Acinetobacter sp.
colomycin (400-800
mg/kg/day)
Tigecycline 100 mg IV loading dose For vancomycin-resistant
then 50 mg IV q12 Enterococci
For ESBL-producing
Enterobacteriaceae (except
Pseudomonas spp.
Ampicillin 1-2 g IV q6-8h For susceptible enterococcal
infections
Cefepime 1-2 g IV q8-12h For Pseudomonas or
Ceftazidime 1-2 g IV q8h+ Acinetobacter spp. infections
Piperacillin-Tazobactam 4.5 g IV q24
Levofloxacin 750 mg q24h For mild infections with no history
of previous third generation
cephalosporin or fluoroquinolone
use
Fluconazole For fungal infections (see Section
Amphotericin B ± on Urinary Candidiasis and
5-flucytosine Candida Urinary Tract Infections
for dosing regimens)
1
Ertapenem – Normal renal function and creatinine clearance (CrCl) >50-90: 1g IV q24h; CrCl <30: 500mg IV q24h
2
Doripenem- CrCl >50-90: 500mg IV q8h; CrCl 30-50: 250mg q8h; CrCl 10-30: 250mg q12h; CrCl <10 no data
3
Imipenem- CrCl >50-90: 250-500mg q6-8h; CrCl 10-50: 250mg q8-12h; CrCl 125-250mg q12h
4
Meropenem- CrCl >50-90: 1g IV q8h; CrCl 10-50: 1g IV q12h; CrCl <10: 500mg IV q24h
5
Risk factors for staphylococcal infection include: presence of an invasive medical device, surgical procedures like joint
replacement, and contact with devices found in a hospital setting, immunocompromised state (HIV, cancer, or
chemotherapy), enteral feeding, prolonged or recent hospitalization, prior levofloxacin or macrolide use[19].
6
Colomycin- Creatinine 1.3–1.5mg/dL: 2 million IU q12h; creatinine 1.6–2.5 mg/dL: 2 million IU q24h; creatinine ≥2.6 mg/dL:
2 million IU q36h
84
6. What is the approach to the presence of the indwelling urinary catheter

once the diagnosis of CA-UTI is made?
a. Whenever possible, the indwelling catheter should be removed

to help eradicate the bacteriuria.
b. For patients in whom indwelling bladder catheterization is

necessary, long-term indwelling catheters should be replaced
with new catheters before initiating antimicrobial therapy for
symptomatic UTI.
Summary of Evidence
In a RCT, removal of the catheter resulted in the spontaneous resolution of
bacteriuria within 14 days.30 This was seen more frequently in women who were 65
years old and younger. In a Cochrane review that looked into short-term catheter
policies after urogenital surgeries in adult patients, the relative risk of catheter-
associated bacteriuria when the catheter was removed earlier (1 day vs. 3 days) was
0.50 (95% CI 0.29, 0.87) demonstrating benefit of early catheter removal. 31
An open clinical trial where symptomatic patients (n=54) with a chronic
indwelling catheter and a clinical diagnosis of UTI were randomized to either indwelling
catheter replacement before initiating antimicrobial therapy or no replacement showed
results favoring catheter replacement. 32 For both groups, initial antimicrobial therapy
consisted of 400 mg ciprofloxacin or 300 mg ofloxacin IV every 12 hours then shifted to
oral 500 mg ciprofloxacin or 200 mg ofloxacin twice daily once patients were afebrile
for 24 hours. Polymicrobial bacteriuria significantly decreased 3 days after therapy was
initiated, and 7 and 28 days after it was discontinued, in 24 versus 8 (p=0.002), 18
versus 9 (p=0.01) and 13 versus 5 (p=0.02) patients, respectively. Catheter
replacement was also associated with a shorter time to afebrile status, improved clinical
status 72 hours after the initiation of therapy in 25 versus 11 patients (p<0.001) and a
lower rate of symptomatic clinical relapse 28 days after therapy in 3 versus 11 patients
(p=0.015).
Comment: Observations should not be generalized to patients on short-term

catheterization since bacterial biofilm formation is not likely to be as important. Some
studies report that urine specimens for culture obtained via a chronic indwelling catheter
yield a greater number of organisms isolated than specimens obtained from a newly
inserted catheter in the same patient. 33
7. What strategies are effective in reducing the risk of CA-UTI?

It is recommended that appropriate strategies for the
prevention of CA-UTI (listed in Table 15) be included and implemented
in an institution-specific, multimodal, quality improvement bundle.
Periodic assessment of compliance with these bundles, once instituted,
is likewise recommended.
85
Table 15. Strategies for reducing the risk of CA-UTI

Use indwelling catheters only when necessary Strong Low
Use aseptic technique including appropriate Strong Low to
hand hygiene and sterile gloves Moderate
Allow only trained health personnel to insert Weak Low
Foley catheters
Properly secure catheters after insertion to Weak Low
prevent
movement and urethral traction
Maintain a closed sterile drainage system. Strong Moderate
Maintain good hygiene at the catheter-urethral Strong Moderate
interface.
Maintain unobstructed urine flow Strong Moderate
Remove catheters when no longer needed. Strong High
Do not change indwelling catheters or drainage Weak Low
bags at fixed intervals.
Summary of Evidence
It is unfortunate that many studies have reported inappropriate use of urinary
catheters in as much as 21% to 50% of cases.1,34,35 More importantly, continued
catheter use was deemed inappropriate for almost half of the days that patients were
catheterized in one study and for over one-third of the days that patients were
catheterized in another prospective evaluation.36,37 Limiting unnecessary
catheterization will ultimately cause reduction in the occurrence of CA-ASB and CA-
UTI.
Appropriate indications for indwelling urinary catheter use in hospitalized
patients are the following: (1) when accurate and frequent measurements of urine
output in critically ill patients are needed; (2) to aid in urologic surgery or other surgery
of contiguous structures; (3) to relieve anatomic or functional urinary tract obstruction
(e.g., patients with neurogenic bladder dysfunction, urinary retention or other congenital
or acquired urologic abnormalities); (4) when urinary incontinence is present without
obstruction in a patient with an open sacral or perineal wound; and (5) just before,
during or just after prolonged surgical procedures with general or spinal anesthesia. 38-
43
Routine catheterization of patients who will undergo caesarian section was
unnecessary based on a systematic review of 3 trials (2 RCTS 1 non-RCT) with a total
of 1,084 participants. Non-catheterized patients had lower incidence of UTI (RR 0.08
95% CI 0.01 to 0.64 for the 2 RCTs), lower rate of discomfort at first voiding and less
time until first voiding.44
Hand hygiene is regarded as the most effective measure to prevent cross-
transmission of potentially harmful organisms. Direct evidence of its effect on
nosocomial infection is scarce, but data showing at least a temporal relationship are
available. Carriage of exogenous organisms on the hands of hospital personnel causing
cross-infections in patients has been implicated in reports of case clusters and
epidemics of nosocomial UTI.45-47 The role of cross-infection was demonstrated in a
prospective study of case clustering in 15.5% of non-epidemic nosocomial bacteriuria
of which 90% of clustered cases and 71 % of non-clustered cases were associated with
86
indwelling urinary catheters.48 Hand washing before and after catheter care have been
emphasized to minimize the risk of personnel hand contamination and to prevent cross
infection.43,49,50 Constant reminder and emphasis on hand hygiene, together with spatial
separation of infected catheterized patients have been documented to control
outbreaks of catheter-associated urinary tract infections.45,46
A greater frequency of catheter-associated bacteriuria 48 hours after errors in
catheter care by hospital personnel was observed than when there were no lapses in
sterile technique or care of the closed drainage system. 51 In this study, bacteriuria
occurred in 13.3% when the catheter-tubing junction had been disconnected at least
once, and in 9.5% with closed catheter-tubing junction; 17.9% of cases acquired
bacteriuria when improper technique was observed against 11.8% when done properly.
However, the differences were not statistically significant. In another study,
disconnection of the catheter junction was associated with a higher rate of infection
than when there was no disconnection. 52 More importantly, adherence to the sterile
continuously closed system of urinary drainage reduced the rate of infection to 16% to
23% from an ineviTable 120% at 4 days after insertion when open drainage was
used.39,51,53 However, infection becomes almost 100% by 30 days with closed
drainage.51,54 Thus, the principal benefit of closed drainage is to delay, if not prevent,
the onset of infection.
Use of aseptic technique and sterile equipment by trained personnel was
shown to be a cost-effective application of the CDC guideline for the prevention of
catheter-associated UTI.43,55 Specifically, these include the use of sterile gloves, sterile
catheters, antiseptic solution for perineal cleansing, and water-soluble lubricating jelly
for catheter insertion.43,55,57 One study noted that within 48 hours of catheterization,
women catheterized by licensed practical nurses and registered nurses had more than
thrice (34%) and twice (21%) the rate of acquired bacteriuria, respectively, than patients
catheterized by trained physicians (10%). 51 One small RCT on 156 patients who
underwent pre-operative catheterization compared sterile catheterization (scrubbing for
four minutes, gowning up, wearing sterile gloves and using strict aseptic technique)
versus clean, non-sterile technique, which involved washing the hands once using soap
and water only. The trial found no significant difference in the development of UTI
between the two groups (9.4% with sterile technique vs. 11% in the hand wash non-
sterile group).58 A larger RCT of 436 obstetric patients whose periurethral area was
cleaned with water vs. chlorhexidine 0.1% before insertion of the urine catheter also
found no significant difference in the rates of UTI (water group 8.2% vs. antiseptic group
9.2%; OR 1.13; 95% CI 0.58, 2.21).59
Interestingly, one small RCT of 177 females undergoing abdominal
hysterectomy that examined whether UTI could be reduced by reversing the sequence
of vaginal cleansing and urethral catheterization found no significant reduction in the
incidence of UTI among those catheterized before vaginal cleansing (15%) versus
those catheterized after vaginal cleansing (25%). 60
Comment: The follow-up period was short for both RCTS: 3 days post-operatively and
24 hours post-insertion of the catheter.58,59 In resource-constrained settings, simple
hand-washing with soap and water and cleaning of the periurethral area with water
before insertion of a sterile catheter with gloved hands may be acceptable alternatives.
87
High bacterial colony counts can develop in the collection bag and ascend
against the flow of urine to infect the urinary bladder within 2 days. 39,51,61 To achieve
free flow of urine: (1) the collection bag should be lower than the level of the bladder at
all times; (2) the catheter and collecting tube should be kept from kinking; (3) the
catheter should not be clamped except when a culture specimen is collected or when
the patient must be separated from the drainage bag; and (4) the bag should be emptied
regularly.43,62
The most important and consistently demonstrated risk factor for developing
bacteriuria is the duration of indwelling catheterization. 2,37,51 CA-UTI occurs at a rate of
3% to 16% per day of catheterization, and at 30 days, almost 100% of catheterized
patients will demonstrate bacteriuria. 39,42,51,57 Maki and Tambyah demonstrated that the
risk is highest at beyond 6 days (OR 5.1 to 6.8). 6 Two prospective studies have
demonstrated that a substantial proportion of catheter days were unnecessary, and
prompt removal would have theoretically prevented 40% of all infections. 36,37 Thus, if
the catheter can be removed before bacteriuria develops, postponement of bacteriuria
becomes prevention.42 A well-conducted prospective study by Domingo and colleagues
(1999) at the medical wards and ICU of the Philippine General Hospital likewise showed
that duration of catheterization was significantly associated with acquisition of infection
(OR 1.22; 95% CI 1.09, 1.37) on multivariate analysis. 7 The study also showed that
peak incidence of CA- UTI occurred on the 5th to 7th day of catheterization. The average
number of days from catheter insertion to the development of UTI was 6.4 days (range
2-44 days). Since duration of catheterization is a modifiable risk factor, emphasis should
be made on interventions to reduce the prolonged and inappropriate use of urine
catheters to decrease the incidence of CA-UTI.
When requesting for urine culture, urine specimens should be obtained
aseptically without opening the catheter-collection. It has been emphasized that the
junction of the catheter and drainage tube should not be disconnected for this
purpose.51,52,63,64 As previously discussed, disconnection of the catheter junctions,
whether to collect urine specimens or to irrigate the bladder, was associated with high
rates of infection.51,52
More recently published literature have looked into the usefulness of
comprehensive programs using a combination of proven individual strategies to reduce
the overall risk of CA-UTI of individual patients and overall CA-UTI rates on an
institutional level.1,5,10,15-19,34,65 An example of a fish diagram that demonstrates the
complexity of factors that lead to the development of CA-UTI is shown in Figure 1. This
type of analysis can be used as a basis for a multimodal or institutional approach to the
prevention of CA-UTI. The roles of infection control committees, therapeutics or
infectious disease specialists as well as surveillance teams are emphasized to provide
specific guidance applicable to their particular clinics, wards and ICUs, hospitals,
nursing homes and other similar healthcare facilities where there is use of urinary
catheters. This paradigm shift is best exemplified by the approaches of the Society of
Healthcare Epidemiology of America and the Association for Professionals in Infection
Control and Epidemiology (APIC) with their document Guide to the Elimination of
Catheter-Associated Urinary Tract Infections (CA-UTIs): Developing and Applying
Facility-based Interventions in acute and Long-term Care Settings an APIC Guide 2008
(APIC 2008).34,35
The healthcare bundle approach which has gained popularity is endorsed by
various groups including the Institute of Healthcare Improvements. This group of
88
89
interventions has been shown to reduce the occurrence of CA-UTI and is well accepted
by health professionals. An example of an institutional bladder bundle would include: 19
Aseptic insertion and proper maintenance of catheter.
Use of bladder ultrasound to fully assess the need for and limit unnecessary
indwelling catheterization.
Use condom or intermittent catheterization in appropriate patients.
Early removal of the catheter using reminders or stop orders.
8. Is condom catheter a reasonable alternative to indwelling

catheterization in the prevention of CA-UTI?
Condom catheterization is an alternative to indwelling catheter for male

patients in whom a urinary catheter is necessary provided post-void
residual urine is minimal and the patient has no cognitive impairment.
Summary of Evidence
In males, the use of external condom catheters has been seen to significantly
reduce the risk for CA-UTI in most studies. A randomized trial involving 75 men at the
US Veterans Affairs Hospital showed that indwelling urethral catheter was associated
with a 5-time increased risk for CA-UTI compared to appropriately sized condom
catheters (HR 4.84; 95% CI 1.46, 16.02; p=0.01). 66
9. Is intermittent catheterization a reasonable alternative to indwelling

catheterization to prevent CA-UTI?
Intermittent catheterization can also be considered an alternative to

short term (strong recommendation, moderate quality of evidence) or long-
term (weak recommendation, moderate quality of evidence) indwelling
urinary catheterization with trained and dedicated healthcare staff.
Intermittent catheterization, however, requires more manpower hours
as well as the full cooperation of patients for frequent repeated
catheterization.
Summary of Evidence
Comparison of intermittent catheterization and indwelling catheterization
shows lower CA-UTI, pyelonephritis, epididymitis, periurethral abscesses, urethral
stricture, vesicourethral reflux, hydronephrosis, calculi and autonomic dysreflexia
among those who undergo intermittent catheterization. 3 In a 38-month prospective
study by Esclarin de Ruz et al with 128 cases of acute spinal cord injuries, the incidence
rates per 100 person days for CA-UTI were 2.72 cases for men with indwelling urethral
catheters, 0.41 cases for men with clean intermittent catheterization, 0.36 cases for
men with condom catheters, and 0.34 cases for women with suprapubic
catheterization.67 The benefit of intermittent catheterization over short-term indwelling
catheterization is better studied than long-term catheterization.
A Cochrane review (that found two trials) showed that catheter-associated
bacteriuria occurred significantly more in patients with indwelling urethral
catheterization (RR 2.90; 95% CI 1.44, 5.84).68 Intermittent catheterization however
90
requires more manpower hours as well as the full cooperation of patients for frequent
repeated catheterization; thus, it is still not a popular choice despite the evidence.
10. Is suprapubic catheterization an alternative to urethral catheterization?

Suprapubic catheterization may be an alternative to urethral
catheterization when there are excellent support mechanisms from the
surgical and caregiver staff.
Summary of Evidence
In a Cochrane review of 14 randomized and quasi-randomized trials which
compared indwelling urethral versus suprapubic catheterization, patients with urethral
catheters showed more cases of catheter-associated bacteriuria (RR 2.60; 95%CI 2.12,
3.18); more re-catheterization (RR 4.12; 95% CI 2.94, 7.56) and greater discomfort (RR
2.98; 95% CI 2.31, 3.85).68 Despite the better results with suprapubic catheters,
experience is limited because of the invasive nature of the insertion requiring this to be
done in the operating room by a skilled surgeon with risks for bleeding and visceral
injury, as well as the need for specially trained caregivers to give continuing
maintenance care.
11. What should NOT be done for patients with urinary catheters?
The following should NOT be done in an effort to reduce CA-UTI because
their use has not been shown to prevent the development of subsequent
bacteriuria or symptomatic UTI:
Table 16. Interventions NOT proven to reduce CA-UTI

Use of antibiotic–coated catheters Strong High
Routine use of systemic prophylactic Strong Moderate
antibiotics at the time of insertion, during
and upon removal of indwelling urinary
catheters
Catheter or bladder irrigation with Strong High
antimicrobial agents
Routine addition of antibiotics or Strong High
antiseptics to drainage bags and antireflux
vents and valves
Daily meatal care Strong High
Changing of catheters and drainage bags Weak Low
at arbitrarily fixed intervals
Summary of Evidence
Antibiotic-coated catheters
Despite the large amount of studies done with various catheter products,
results are variable. In a Cochrane review of 23 randomized and quasi randomized
trials, the following were shown: (1) silver oxide catheters were not associated with
reduction in catheter-associated bacteriuria; and (2) silver alloy catheters showed lower
91
incidence of CA-ASB if catheterized for less than 1 week (RR 0.54; 95% CI 0.43, 0.67)
and if for more than 1 week (RR 0.64; 95%CI 0.51, 0.80).69 On the other hand, a larger
study involving 3,036 patients comparing various catheters including silicone-based
silver hydrogel coated catheters versus silicone-based hydrogel coated catheters
showed no difference in protection against catheter-associated bacteriuria.70
When antibiotic-coated catheters were tested, a Cochrane review showed
reduced rates of catheter-associated bacteriuria in minocycline and rifampin-coated
catheters compared to standard catheters if used for less than 1 week (RR 0.36; 95%CI
0.18, 0.73) but not at more than 1 week. 71 Nitrofurazone-coated catheters were also
associated with lower rates of catheter-associated bacteriuria at less than 1 week
catheterization (RR 0.52; 95% CI 0.34, 0.78) but the benefit when used more than 1
week is less conclusive.
A recent parallel, three-group, multicenter, randomized controlled superiority
trial enrolled 6,394 adult participants requiring short-term catheterization randomly
allocated to receive a silver alloy-coated catheter, a nitrofural-impregnated catheter, or
a standard polytetrafluoroethylene-coated catheter (control group).72 Results showed
that symptomatic UTI (primary outcome) occurred in 12.6%, 12.5% and 10.6% in the
control group, silver alloy group and the nitrofural catheter group respectively, with the
difference considered to be clinically insignificant. While the nitrofural catheter group
appear to have lower rates of symptomatic infection, it was noted that the rate of
catheter-related discomfort was higher in this group than with the control and silver alloy
group. The study concluded that routine use of antimicrobial-impregnated catheters
was not supported.
Systemic prophylactic antibiotics

One small RCT of 70 patients with long-term urinary catheters demonstrated
that the use of prophylactic antibiotic during routine replacement of the catheter did not
prevent or delay the development of bacteriuria.73 A meta-analysis aimed to determine
whether antibiotic prophylaxis at the time of removal of a urinary catheter reduces the
risk of subsequent symptomatic UTIs was done recently. 74 It included six RCTs and one
non-randomized controlled study with variable methodological quality ranging from low
to moderate. They were heterogeneous in the type and duration of antibiotic
prophylactic regimen used. The meta-analysis reported over-all benefit with the use of
antibiotic prophylaxis in reducing the risk for CA-UTI (RR 0.45; 95% CI 0.28, 0.72) with
a number-needed-to-treat of 17 (12 to 30). However, it is important to note that these
studies were mostly confined to surgical patients such as males undergoing
prostatectomy or other surgical operations. In addition, the study defined UTI as
detection of measurable bacteriuria plus the presence of at least one sign or symptom.
This definition may have overestimated the prevalence of UTI in the early post-
operative period since most post-surgery patients complain of lower urinary tract
complaints and develop bacteriuria without necessarily having UTI. 75 More randomized
trials using similar treatment regimens are needed to support the use of antibiotic
prophylaxis after catheter removal. Because of this reason and the increased risk for
the development of adverse drug reactions, additional costs, and the possibility of
emergence of resistant bacteria, routine antibiotic use to postpone bacteriuria or treat
asymptomatic bacteriuria among catheterized patients is discouraged. 13,42,76,77
92
Bladder irrigation
RCTs have shown that bladder irrigation using antimicrobial agents did not
prevent most catheter-associated bacteriuria even if given continuously. 78-82 One cross-
over study that included 32 women on long-term catheterization showed that 10 weeks
of daily bladder irrigation with normal saline was similar to 10 weeks of no irrigation in
terms of catheter-associated bacteriuria, catheter obstruction and febrile episodes. 83
Addition of disinfectants or antiseptics to drainage bags

Instillation of disinfectants in the drainage bags or the use of antireflux vents
and valves did not reduce the incidence of bacteriuria in RCTs.50,84-87
Daily meatal care

It seems logical that daily meatal care at the urethra-catheter interface would
decrease bacterial colonization and thereby prevent subsequent UTI. However, large
randomized trials have consistently shown no benefit with enhanced meatal care using
povidone-iodine, silver sulfadiazine and polyantibiotic ointment or cream. 53,62,88
On the contrary, one study that compared three groups: Group 1 – twice daily
application of povidone-iodine at the urethra-catheter junction; Group 2 – once daily
application of a non-antiseptic solution of green soap and water; and Group 3 – routine
care (debris removal at usual baths), reported higher rates of catheter-associated
bacteriuria in both treatment groups compared with routine care. 88 The proposed
reasons for the lack of demonstrable advantage of this strategy include the lack of effect
on the ascending route of infection within the catheter lumen; short-lived antiseptic
effect of the topical agents; increased catheter manipulation during cleaning; and the
development of protective biofilms on the surface.3
Catheter change at arbitrarily fixed intervals

Biofilms produced on the surface of catheters over time protect pathogens
from antibiotic agents and from the patient’s own immune response. 41 The practice of
changing indwelling catheters on a routine schedule is based on the idea of decreasing
microbial burden and biofilm formation as well as minimizing the likelihood of blockage
and stasis. Due to lack of sufficient scientific evidence to support this strategy, experts
agree that a catheter should not be changed routinely on a periodic interval. 3,43,89
Indications for catheter and drainage bag change include: (1) malfunction or leakage;
(2) catheter obstruction; (3) contamination (e.g., disconnection between catheter and
drainage tube); (4) bacteriuria that require antibiotics; (5) concretions in catheter lumen
that may proceed to its obstruction; and (6) candiduria. 89
12. How can unnecessary long-term catheterization be avoided?

Consider using alternative strategies for timely removal and prevention
of unnecessary long-term catheterization such as instituting automatic
stop orders, nurse-based or electronic physician reminder systems or
chart reminders.
Weak recommendation, Moderate quality of evidence
Summary of Evidence
Small studies on quality improvement interventions aimed to decrease
duration of catheterization have shown small significant changes. For instance, a recent
93
small before-and-after crossover study in a US medical center found that computerized

urinary catheter reminder system decreased catheterization duration by nearly 3 days
(p=0.1).90 In a pre-post intervention study, healthcare worker education and the
provision of an “indication sheet” for the use of urinary catheters prove to be effective
in reducing the total number of catheters placed (2,029 in 2001; to 2,188 in 2002; 300
in 2004; and 512 in 2005).91 A systematic review published in 2013, in fact, reported a
53% decrease in the rate of CA-UTI when these reminder strategies are put in place. 92
Locally, a quality improvement project using written chart reminders
decreased the duration of catheterization by 1.4 days (Domingo 2003). Although UTI
rates were not measured, quality improvement interventions (e.g., automatic stop
orders or chart reminders) are promising and may prove beneficial if sustained in the
long term.
Comment: In one of the study sites of a collaborative quality improvement project, the
use of written chart reminders in a provincial hospital in the Philippines reduced
inappropriate catheter use from 32% to 15% over a period of 6 months in a time-series
analysis. [Abstract presented at the 2004 Asia Pacific Society for Infection Control
Conference and the 2004 International Conference on Improving the Use of Medicines].
The 2012 European Urology Association Guidelines on Urological Infections

and the 2009 IDSA Guidelines on the Diagnosis, Prevention and Treatment of CA-UTI
in Adults have both enumerated strategies such as automatic stop orders, electronic-
based or nurse-based reminders (when possible) that may aid in minimizing catheter
days.3,93
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40. Munasinghe RL, et al. Appropriateness of Use of Indwelling Urinary Catheters in Patients
Admitted to the Medical Service. Infect Control Hosp Epidemiol 2001;22(10):647-649.
41. Saint S, Chenoweth CE. Biofilms and catheter-associated urinary tract infections. Infect Dis
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42. Warren JW. Catheter-associated urinary tract infections. Infect Dis Clin North Am 1997;
11:609–622.
43. Wong ES. Guideline for prevention of catheter-associated urinary tract infections. Am J Infect
Control 1983 Feb;11(1):28-36.
44. Li L, Wen J, Wang L, Li YP, Li Y. Is routine indwelling catheterization of the bladder for
caesarean section necessary? A systematic review. BJOG 2011; 118:400-409
45. Kaslow RA, Lindsey JO, Bisno AL, Price A. Nosocomial infection with highly resistant, Proteus
rettgeri. Report of an epidemic. Am J Epidemiol. 1976 Sep;104(3):278-86.
46. Maki DG, Hennekens CG, Phillips CW, Shaw WV, Bennett JV. Nosocomial urinary tract
infection with Serratia marcescens: an epidemiologic study. J Infect Dis. 1973 Nov;128(5):579-
87.
47. Schaberg DR, Weinstein RA, Stamm WE. Epidemics of nosocomial urinary tract infection
caused by multiply resistant gram-negative bacilli: epidemiology and control. J Infect Dis. 1976
Mar;133(3):363-6.
48. Schaberg DR, Haley RW, Highsmith AK, Anderson RL, McGowan JE Jr.Nosocomial
bacteriuria: a prospective study of case clustering and antimicrobial resistance. Ann Intern
Med. 1980 Sep;93(3):420-4.
49. Garner JS, Favero MS.CDC guidelines for the prevention and control of nosocomial infections.
Guideline for handwashing and hospital environmental control, 1985. Supersedes guideline for
hospital environmental control published in 1981. Am J Infect Control. 1986 Jun;14(3):110-29.
50. Steere AC, Mallison GF. Handwashing practices for the prevention of nosocomial infections.
Ann Intern Med. 1975 Nov;83(5):683-90.
51. Garibaldi RA, Burke JP, Dickman ML, Smith CB. Factors predisposing to bacteriuria during
indwelling urethral catheterization. N Engl J Med. 1974 Aug 1;291(5):215-9.
52. Warren JW, Platt R, Thomas RJ, Rosner B, Kass EJ. Antibiotic irrigation and catheter-
associated urinary tract infections. N Engl J Med 1978;299:570-3.
53. Kass EH, Sossen HS. Prevention of infection of urinary tract in presence of indwelling
catheters; description of electromechanical valve to provide intermittent drainage of the
bladder. J Am Med Assoc. 1959 Mar 14;169(11):1181-3/
54. Burke JP, Larsen RA, Stevens LE. Nosocomial bacteriuria: estimating the potential for
prevention by closed sterile urinary drainage. Infect Control. 1986 Feb;7(2 Suppl):96-9.
55. Epstein SE. Cost-effective application of the Centers for Disease Control guideline for
prevention of catheter associated urinary tract infections [abstract]. Am J Infect Control 1985;
13:272-75
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56. Desautels RE, Walter CW, Graves RC, Harrison JH. Technical advances in the prevention of
urinary tract infection. J Urol. 1962 Mar;87:487-90.
57. Kass EH, Schneiderman LJ. Entry of bacteria into the urinary tracts of patients with inlying
catheters. N Engl J Med. 1957 Mar 21;256(12):556-7.
58. Carapeti EA, Andrews SM, Bentley PG. Randomised study of sterile versus non-sterile urethral
catheterisation. Ann R Coll Surg Engl. 1996 Jan;78(1):59-60.
59. Webster J, Hood RH, Burridge CA, Doidge ML, Phillips KM, George N. Water or antiseptic for
periurethral cleaning before urinary catheterization: a randomized controlled trial. Am J Infect
Control. 2001 Dec;29(6):389-94.
60. Chan YM, Ngai SW, Hon E, So WK. Could the incidence of postoperative urinary tract infection
be reduced by reversing the sequence of vaginal cleansing and urethral catheterisation? J
Hosp Infect 2000;46:67-72.
61. Thornton GF, Andriole VT. Bacteriuria during indwelling catheter drainage. II. Effect of a closed
sterile drainage system. JAMA 1970 Oct 12;214(2):339-42
62. Reese RE, Betts RF editors. Catheter-associated UTI. A practical approach to infectious
disease 4th ed. 1997; 12:506-11.
63. Huth TS, Burke JP, Britt MR, et al. Randomized trial of meatal care with silver sulfadiazine
cream for the prevention of catheter-associated bacteriuria. J Infect Dis 1992;165:14-18.
64. Platt R. Quantitative definition of bacteriuria. Am J Med 1983;75:44-52.
65. Carr HA. Catheter-associated Urinary Tract Infections in Adults. Prevention through Care and
Technology. Infection Control Today 1998;2(8):26-29.
66. Saint S, Kaufman SR, Rogers MA, et al. Condom versus indwelling urinary catheter: a
randomized trial. J Am Geriatr Soc 2006:54:1055-1061.
67. Esclarin de Ruz A, Garcia Leoni E, Herruzo Cabrera R. Epidemiology and risk factors for
urinary tract infection in patients with spinal cord injury. J Urol 2000;164:1285-1289.
68. Niel-Weise BS, van den Broek PJ. Urinary catheter policies for short term bladder drainage in
adults. Cochrane Database Syst Rev 2005:CD004203.
69. Schumm K, Lam TB. Types of urethral catheters for management of short-term voiding
problems in hospitalized adults. Cochrane Database Syst Rev 2008: CD004013.
70. Srinivasan A, Karchmer T, Richards A et al. A prospective trial of a novel, silicone based silver
coated foley catheter for the prevention of nosocomial urinary Tract infections. Infect Control
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71. Darouiche RO, Smith JA Jr, Hanna H et al. Efficacy of antimicrobial impregnated bladder
catheters in reducing catheter-associated bacteriuria: a prospective randomized multicenter
clinical trial. Urology 1999;54:976-981.
72. Pickard R, Lam T, MacLennan G, Starr K, et al. Antimicrobial catheters for reduction of
symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a
multicentre randomised controlled trial. Lancet. 2012 Dec 1;380(9857):1927-35.
73. Firestein M, Mendelson G, Gronich D, Granot E, Ben-Israel J, Raz R. Can antibiotic use during
routine replacement of long-term urinary catheter prevent bacteriuria? Inf Dis Clin Practice
2001;10:133-35.
74. Marschall J, Carpenter CR, Fowler S, Trautner BW for the CDC Prevention Epicenters
Program. Antibiotic Prophyaxis for urinary tract infections after removal of urinary catheter;
meta-analysis. BMJ 2013;346:f3147.
75. Rowland PS. Rapid response to: Antibiotic Prophyaxis for urinary tract infections after removal
of urinary catheter; meta-analysis. BMJ 2013 Jun. Available at
http://www.bmj.com/content/346/bmj.f3147/rr/650697. Accessssed on 14 August 2013.
76. Mountokalakis T, Skounakis M, Tselentis J. Short-term versus prolonged systemic antibiotic
prophylaxis in patients treated with indwelling catheters. J Urol. 1985 Sep;134(3):506-8.
77. Schaberg DR, Zervos MJ. Nosocomial urinary tract infection. Compr Ther. 1986 Apr;12(4):8-
11.
78. Bastable JR, Peel RN, Birch DM, Richards B. Continuous irrigation of the bladder after
prostatectomy: Its effect on post-prostatectomy infection [abstract]. Br J Urol 1977;49:689-93.
79. Davies AJ, Desai HN, Turton S, Dyas A. Does instillation of chlorhexidine into the bladder of
catheterized geriatric patients help reduce bacteriuria. J Hosp Infect 1987;9:72-75.
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80. Gillespie WA, Simpson RA, Jones JE, Nashef L, Teasdale C, Speller DC. Does the addition of
disinfectant to urine drainage bags prevent infection in catheterized patients? Lancet
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81. Warren JW, Platt R, Thomas RJ, Rosner B, Kass EJ. Antibiotic irrigation and catheter-
associated urinary tract infections. N Engl J Med 1978; 299:570-3.
82. Maki DG, Hennekens CH, Bennett JV. Prevention of catheter-associated urinary tract infection.
An additional measure. JAMA 1972 Sep 11;221(11):1270-1.
83. Muncie HL Jr., Hoopes JM, Damron DJ et al. Once-daily irrigation of long-term urethral
catheters with normal saline; lack of benefit. Arch Intern Med 1989; 149:441-3.
84. Sweet DE, Goodpasture HC, Holl K, Smart S, Alexander H, Hedari A. Evaluation of H202
prophylaxis of bacteriuria in patients with long-term indwelling foley catheters: a randomized
controlled study [abstract]. Infect Control 1985;6:263-6 .
85. Thompson RL, Haley CE, Seacy MA, et al. Failure to reduce attack rates using periodic
instillations of a disinfectant into urinary drainage systems. JAMA 1984;251:747-51.
86. Willie JC, Blusse van Oud Alblas A, Thewessen EA. Nosocomial catheter-associated
bacteriuria: a clinical trial comparing two closed urinary drainage systems [abstract]. J Hosp
Infect 1993;25:191-8.
87. Keys TF, Maker MD, Segura JW. Bacteriuria during closed urinary drainage: an evaluation of
top-vented versus bag vented systems J Urol 1979;122:49-51.
88. Burke JP, Garibaldi RA, Sullivan MR, et al. Prevention of catheter-associated urinary tract
infections: efficacy of daily meatal care regimens. Am J Med 1981;70:655-8.
89. Stamm WE, Hooton TM. Management of urinary tract infection in adults. N Engl J Med 1993;
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90. Cornia PB, Amory JK, Fraser S, Saint S, Lipsky BA. Computer-based order entry decreases
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strategies to prevent catheter-associated UTI: an integrative review. BMJ Qual Saf 2014: April
23(4):277-89.
98
Renal abscess
RENAL ABSCESS
1. When should renal abscess be suspected in patients presenting with upper
urinary tract infection (UTI)?
Renal abscess should be strongly considered in diabetic patients presenting

with hypotension and renal impairment. It can also be considered for
patients suspected to have upper UTI who remain febrile and hypotensive 72
hours after initial intravenous (IV) antibiotic administration.
2. What are the diagnostic tests to be done in patients suspected of having

renal abscess?
2.1 Imaging should be done to confirm a diagnosis of renal abscess. A CT

scan is preferred over ultrasound because of the former’s higher
sensitivity.
2.2 Urine and blood cultures should be requested for patients suspected
of having renal abscess. An abscess aspirate, if drainage has been
performed, should be sent for culture studies.
3. In patients diagnosed with renal abscess, when is surgical intervention
warranted?
3.1 For lesions less than 5 cm in diameter, antibiotics can be given alone
and should be continued for 4-10 weeks until the abscess has
completely regressed as evidenced by CT scan. Drainage need not be
done.
3.2 Percutaneous drainage should be considered for renal and perirenal
abscesses with sizes >5 cm. Open drainage should be considered for
those with multiloculated abscesses and for those patients in whom
percutaneous drainage is unsuccessful. Antibiotics should be given
for a minimum of four weeks after drainage.
3.3 For patients treated with antibiotics alone, CT scan imaging should be
repeated after four to six weeks.
4. What empiric antibiotics should be started on those suspected to have renal
abscess?
4.1 The antibiotics chosen should have activity against gram-negative
organisms, particularly Escherichia coli, Klebsiella sp., and Proteus
mirabilis. Empiric antibiotics should be guided by local antimicrobial
susceptibility patterns.
99
Renal abscess
Always assess for patients’ risk factors for drug resistance/ESBL-

production and Pseudomonas infection when choosing empiric
antibiotics. Antibiotics listed in the general guidelines in the
management of complicated UTI may be used. Similarly, when other
drug-resistant pathogens are considered, the antibiotics listed in the
Table of antibiotic options for CA-UTI (Table 14) may be used.
4.2 Vancomycin can be added for coverage of Staphylococcus aureus if

there is another source of infection where S. aureus is suspected.
100
Renal abscess
DISCUSSION
1. When should renal abscess be suspected in patients presenting with
upper urinary tract infection (UTI)?
1.1 Renal abscess should be strongly considered in diabetic patients

presenting with hypotension and renal impairment. It can also be considered
for patients suspected to have upper UTI who remain febrile and hypotensive
72 hours after initial intravenous (IV) antibiotic administration.
Summary of Evidence
Occasionally, abscesses can form in the kidneys, and diabetes is an important
risk factor. It can have a high mortality rate if poorly treated.1-5 The common signs and
symptoms of renal abscess, as identified by five retrospective studies, are fever (75–
93% of patients), costovertebral angle tenderness (75%), lumbar pain (36–64.5%),
nausea and vomiting (30%), dysuria (8.9–12%), and anorexia (6–37%).4-8 These signs
and symptoms are similar to the presentation of other complicated UTI syndromes.
However, several conditions would make one suspect renal abscess; such conditions
include the presence of diabetes mellitus (DM), hypotension, renal impairment and the
absence of response to initial antibiotic treatment.
Several studies have identified DM as the most common predisposing factor
for the development of renal and perinephric abscesses. 2,4,5,8,9 The proposed reason
for this predisposition is the defective chemotaxis, phagocytosis and bactericidal activity
of phagocytes in patients with diabetes. 10-12 One study performed an analysis of the risk
factors associated with the development of renal abscess. 7 The study included patients
with suspected upper UTI, as evidenced by clinical symptoms of pyuria and flank pain,
and who underwent computerized tomography (CT) scan imaging to look for evidence
of acute pyelonephritis or renal abscess. Of the 130 study participants, 23 (17.7%) were
diagnosed with renal abscess. On multivariate analysis, DM (OR 5.8 p=0.016),
hypotension (OR 4.7 p=0.044), acute renal impairment (OR 13.4 p= 0.001) and
leukocytosis of more than 20,000/L (OR 22.6 p=0.00) were associated with renal
abscess.7 In a 10-year cohort match control study to investigate the incidence of renal
abscess in Taiwan, a total of 500,522 diabetics and 500,365 non-diabetic controls were
included. There were 2,044 cases of renal abscess documented within the diabetic
group, and these were compared to 448 cases in the control group. Significant factors
associated with renal abscess were DM (HR 3.81 95% CI 3.44–4.23 p=0.00001) and
female gender (HR 2.78 95% CI 2.51–3.088 p<0.0001). In this study, however, DM was
not associated with increased in-hospital mortality rate compared to controls.1
Very few patients with acute UTI will be febrile for more than four days after
antibiotic initiation.13 A retrospective chart review of 70 patients hospitalized for febrile
pyelonephritis reported that only 13% had fever that persisted for up to 72 hours. 14
Another retrospective study involving a chart review of 88 patients was done to identify
clinical characteristics that can lead to early diagnosis of renal abscess. It concluded
that in order to make an early diagnosis of renal abscess, emphasis should be placed
on a protracted UTI course especially if an appropriate antibiotic regimen has already
been started.13 In addition, in one study that stratified patients into three groups based
on disease severity [group 1: simple acute pyelonephritis (n=82), 7.3%; group 2: severe
101
Renal abscess
acute pyelonephritis (n=25), 48%; and group 3: abscess (n=23), 43.5% p<0.001]
occurrence of hypotension was associated with renal abscess formation and more
severe disease.7 On multivariate analysis, DM (OR 5.8 p=0.016) and hypotension (OR
4.7 p=0.044), together with acute renal impairment (OR 13.4 p=0.001), were statistically
significant factors for the development of renal abscess. 7 Failure to respond to
treatment after 72 hours of initial IV antibiotic administration, or clinical failure as
evidenced by persistent hypotension, should make one suspect renal abscess
formation.
2. What are the diagnostic tests to be done in patients suspected of having

renal abscess?
2.1 Imaging should be done to confirm a diagnosis of renal abscess.
A CT scan is preferred over ultrasound because of the former’s
higher sensitivity.
Summary of Evidence
CT scan is the imaging modality of choice in the evaluation of upper UTIs. CT
scan is better than ultrasonography in detecting focal parenchymal abnormalities,
defining the extent of disease and detecting perinephric fluid collections and
abscesses.15,16 Ultrasound, on the other hand, has the advantage of being more
accessible and being less expensive; it can be done at the bedside and there is less
patient exposure to contrast medium or radiation. 17 However, it is less sensitive in
detecting renal abscesses with sizes <3 cm 18 and can miss the diagnosis in as much
as 42.3% of cases.2
A retrospective study of 12 patients diagnosed with renal or perinephric
abscess and nephritis compared the abilities of CT scan and sonography done within
48 hours to detect such lesions. 18 Results showed that for renal abscess,
ultrasonography was able to detect two out of three cases seen on CT scan. For
perinephric abscess, ultrasonography missed one of the three cases identified by CT
scan. In cases of focal or multifocal bacterial nephritis, five cases were identified by CT
scan while only two were seen on ultrasonography. Abscesses that were missed by
ultrasound either have sizes <2 cm (multiple microabscesses) or were gas forming. In
another retrospective study of 66 patients with retroperitoneal abscesses, wherein
72.7% involved the kidney, ultrasonography was diagnostic in 33 of 39 patients (84.6%)
while CT scan was diagnostic in 38 of 40 patients (95%). 19
2.2 Urine and blood cultures should be requested for patients

suspected of having renal abscess. An abscess aspirate, if
drainage has been performed, should be sent for culture studies.
Summary of Evidence
Culture positivity rates reported by several studies were 41–43% for urine,
31–40% for blood and 59% for pus/aspirate specimens.2,4,7,8 Urine and blood cultures
were not highly sensitive and were positive in less than half of cases. 4 However, several
studies have reported that either blood or urine cultures parallel the bacteriology of the
abscess; thus, their results can be used as a guide in the selection of antimicrobial
102
Renal abscess
therapy. One study involving 88 patients with renal or perinephric abscess, with an
88.6% isolation rate of the etiologic organisms (from any specimen such as blood, urine
or abscess aspirate), reported that 37% had identical pathogens in two or three of the
cultures. Urine and abscess culture isolates were the same in 15% of cases, blood and
abscess in 12.8% and blood and urine in only 1.3%. 13 Another retrospective study of
66 patients with retroperitoneal abscess reported higher rates of agreement—41.6% of
urine culture results and 63.1% of blood culture results coincided with the abscess
aspirate culture.19
An abscess aspirate, if drainage has been performed, should be sent for
routine aerobic culture studies. An anaerobic culture can be requested if there is access
to a microbiology laboratory that can perform such. Special media are required when
performing anaerobic cultures (e.g., cooked meat broth), and the timing of inoculation
is very important. Hence, there should be proper coordination ahead of time between
the laboratory and the one who will acquire the samples (via aspiration or surgical
drainage) to ensure adequacy, appropriateness and reliability of specimens.
3. In patients diagnosed with renal abscess, when is surgical intervention

warranted?
3.1 For lesions less than 5 cm in diameter, antibiotics can be given alone and
should be continued for 4-10 weeks until the abscess has completely
regressed as evidenced by CT scan. Drainage need not be done.
3.2 Percutaneous drainage should be considered for renal and perirenal

abscesses with sizes >5 cm. Open drainage should be considered for
those with multiloculated abscesses and for those patients in whom
percutaneous drainage is unsuccessful. Antibiotics should be given
for a minimum of four weeks after drainage.
3.3 For patients treated with antibiotics alone, CT scan imaging should be
repeated after four to six weeks.
Summary of Evidence
In at least six retrospective studies involving patients diagnosed with renal
abscess, clinical regression was seen within 16 days to 16 weeks of antibiotics alone
for abscesses <5 cm in size. 2,4,9,20-22 For abscesses >5 cm in size by CT scan, five
studies have reported favorable outcomes with percutaneous drainage.2,4,5,20,22 One
retrospective study involving 32 patients with renal and perirenal abscesses (average
abscess volume of 10–650 ml, size not specified) reported a cure rate of 67% with
percutaneous drainage alone. Minimal complications were reported. 6 For abscess sizes
between 3–5 cm, recommendations on the decision to treat with antibiotics alone or to
perform drainage are varied.2,4,9,20-22 The decision will ultimately rely on individual
patient scenarios, taking into consideration the severity of infection, location, the
presence of comorbidities and surgical risk assessment, among others.
In a study of 23 patients with abscess (size >3 cm), those treated with
percutaneous drainage seem to have comparable outcomes to those treated directly
103
Renal abscess
with surgical drainage.23 Adjunctive therapy may be warranted only for certain situations
such as the presence of loculation, the presence of a superinfected tumor or when
kidney function is compromised.6 Hence, regular clinical assessment is important in the
course of treatment to guide in the proper timing and selection of appropriate surgical
interventions.
4. What empiric antibiotics should be started on those suspected to have renal

abscess?
4.1 The antibiotics chosen should have activity against gram-negative

organisms, particularly Escherichia coli, Klebsiella sp., and Proteus
mirabilis. Empiric antibiotics should be guided by local
antimicrobial susceptibility patterns.
Always assess for patients’ risk factors for drug resistance/ESBL-

production and Pseudomonas infection when choosing empiric
antibiotics. Antibiotics listed in the general guidelines in the
management of complicated UTI may be used. Similarly, when
other drug-resistant pathogens are considered, the antibiotics
listed in Table 14 (Antibiotic options for CA-UTI) may be used.
4.2 Vancomycin can be added for coverage of Staphylococcus aureus

if there is another source of infection where S. aureus is suspected.
Summary of Evidence
In recent years, gram-negative organisms including E. coli, Klebsiella sp., and
P. mirabilis have been the predominant pathogens isolated from specimens (blood,
urine and abscess aspirate) from patients with renal abscess. 2,5,6,13,24
S. aureus infection of other location may result in bacteremia and metastasis
to the renal parenchyma, resulting in abscess formation. Renal abscess patients with
S. aureus as the pathogen usually have a history of ongoing skin infection. 25,26
104
Renal abscess
Patient suspected with upper UTI presenting with any of

the following? NO
• Hypotension
• Renal impairment
• Failure to respond to IV antibiotics within 72 hours
Continue antibiotics.
YES
Do imaging: CT scan (preferred) or UTZ
If CT scan is negative,
Renal abscess NO renal abscess is unlikely. If
present? UTZ is negative, consider
doing a CT scan.
YES
Continue antibiotics for a
minimum of four weeks;
Size of renal NO antibiotics can be
abscess >5 cm? discontinued upon
resolution of abscess on
repeat CT scan.
YES
Refer to urology for drainage of abscess;

antibiotics are continued for a minimum of four
weeks in a setting of proper drainage.
Figure 2. Management algorithm for the treatment of suspected renal anscess
105
Renal abscess
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107
URINARY TRACT INFECTION IN RENAL TRANSPLANT PATIENTS
1. How should urinary tract infection (UTI) in post–kidney transplant
patients be managed?
1.1 Post-transplant UTI can be managed by initial administration of
empiric broad-spectrum antibiotics. Patients suspected of having
drug-resistant gram-positive infections (e.g., Enterococci,
methicillin-resistant Staphylococcus aureus) should be started on
antibiotics that are active against such organisms. Specific
therapy can be initiated once culture results are available and
should be continued until the pathogen is eradicated.
1.2 Patients with early UTI (i.e., occurring within the first six months
after transplantation) or UTI presenting with signs and symptoms
of pyelonephritis or sepsis should be admitted and started on
intravenous (IV) antibiotics. Treatment should be given for 14
days. When the results of urine culture are available, the IV
antibiotics can be shifted to their oral equivalent (if available and
clinically feasible) to complete the treatment duration.
1.3 Late cystitis (i.e., occurring after six months post-transplant) can
be treated for seven days, while late pyelonephritis requires 14
days of antimicrobial therapy.
1.4 Patients with recurrent and relapsing UTI should be worked up for
any functional or anatomic abnormalities and treated with a longer
course of antibiotic.
2. What is the effective antibiotic prophylaxis for post–kidney transplant

patients to reduce the risk for UTI?
Oral TMP-SMX (160 mg/800 mg) taken twice daily immediately post-
transplant, then once daily as soon as the catheter is removed or the
patient is discharged, continued until 6 months post-transplantation,
reduces the risk of bacteriuria and bacteremia in post–renal transplant
recipients.
108
DISCUSSION
1. How should urinary tract infection (UTI) in post–kidney transplant patients
be managed?
1.1 Post-transplant UTI can be managed by initial administration of

empiric broad-spectrum antibiotics. Patients suspected of having
drug-resistant gram-positive infections (e.g., Enterococci,
methicillin-resistant Staphylococcus aureus) should be started on
antibiotics that are active against such organisms. Specific
therapy can be initiated once culture results are available and
should be continued until the pathogen is eradicated.
1.2 Patients with early UTI (i.e., occurring within the first six months
after transplantation) or UTI presenting with signs and symptoms
of pyelonephritis or sepsis should be admitted and started on
intravenous (IV) antibiotics. Treatment should be given for 14
days. When the results of urine culture are available, the IV
antibiotics can be shifted to their oral equivalent (if available and
clinically feasible) to complete the treatment duration.
1.3 Late cystitis (i.e., occurring after six months post-transplant) can
be treated for seven days, while late pyelonephritis requires 14
days of antimicrobial therapy.
1.4 Patients with recurrent and relapsing UTI should be worked up for
any functional or anatomic abnormalities and treated with a longer
course of antibiotic.
Table 17. Recommended empiric antibiotics for early post–kidney transplant UTI
Gram-Negative Organism Gram-Positive Organism
meropenem vancomycin
ertapenem linezolid
imipenem nitrofurantoin*
doripenem tetracycline*
amikacin
nitrofurantoin*
* Reserved for asymptomatic bacteriuria or cystitis only
Summary of Evidence
The various syndromes of UTI may occur in the setting of kidney
transplantation. Cystitis presents with lower urinary tract symptoms such as frequency,
urgency, dysuria, and hematuria or suprapubic pain. Pyelonephritis, on the other hand,
presents with upper urinary tract symptoms such as rigors and pyrexia, hematuria, loin
109
pain in native kidney and pain over the graft. It is important to take note, however, that
because the innervation of the transplanted kidney is already severed, pain over the
graft may not be present, or it may be difficult to localize. Recurrent UTI is defined as
three or more UTI episodes in a 12-month period, including asymptomatic episodes.
These infections are believed to be caused by different strains of infecting organisms.
Relapsing UTI, on the other hand, results from the inability to eradicate the original
infection. Pyuria is defined as the presence of at least 10 wbc/hpf of unspun midstream
urine.1
UTI in the setting of kidney transplantation is complicated by several factors such as

urologic instrumentation1 and altered anatomy post-transplantation (e.g.,
ureteral anastomosis complications, etc.);2
immunosuppression, which may mask the classical signs and symptoms of
infection;1 and
significant drug interactions (e.g., trimethoprim-sulfamethoxazole [TMP-SMX]
and aminoglycosides may interact with tacrolimus or cyclosporine). 3
As of 2011, the most common organisms isolated from renal transplant patients at
the National Kidney and Transplant Institute (NKTI) were Escherichia coli (46%),
Klebsiella (20.6%) and coagulase-negative Staphylococcus (10.3%). The rate of
extended-spectrum beta-lactamase (ESBL)–producing E. coli was around 12.4% (9%
confirmed, 3.4% probable) while ESBL-producing Klebsiella was 30% (25% confirmed,
5% probable).
Timing of the UTI is the most important factor that determines morbidity from the
infection. Early UTI is defined as UTI occurring within the first six months post-
transplantation, while late UTI is defined as UTI occurring more than six months after
kidney transplantation.4,5 UTI is often associated with acute pyelonephritis and rapidly
develops to bacteremia during the early post-transplant period. In the study by Chuang,
post-transplant UTI was significantly associated with increased mortality (OR 3.5 95%
CI 1.68-7.23).6 Acute pyelonephritis has been shown to be an independent risk factor
for decline in renal function; patients with this disorder get a 3.4-fold increase in their
risk, compared to those who did not develop UTI or those who developed cystitis only.
However, acute pyelonephritis was not associated with increased risk for graft loss; 7-9
neither does it affect patient survival.10
Patients with early UTI post-transplant presenting with acute pyelonephritis should
be admitted and started on empiric IV antibiotics that cover for both gram-positive and
gram-negative organisms. Urine culture and sensitivity should be performed before
initiating empiric antibiotics; however, these should not delay antibiotics administration.
Infection with an ESBL-producing organism should be considered in patients presenting
with urosepsis.
There are currently no randomized trials on the duration of antibiotics for the
treatment for UTI in transplant patients. Previously, it was recommended that
pyelonephritis during the early post-transplant period be treated with antibiotics for six
weeks, based on its treatment success in 13 out of a series of 14 patients. 2 More recent
international guidelines recommend giving antibiotics for at least two weeks, based on
low-quality evidence and as an extension of results from studies among non-transplant
patients.3,11,12
110
Recurrent and relapsing UTI should be worked up for any functional or anatomic
abnormality; the most common causes include ureteral reflux, stricture at the
ureterovesical junction and neurogenic bladder. 3,11,12 There are currently no trials on
the duration of antimicrobial therapy for relapsing or recurrent UTI, but it is
recommended that antimicrobial therapy be given for a longer period of time.
Late UTI was previously considered to be of less clinical significance; however, a
recent study from the United States Renal Data System showed that late UTI was an
independent risk factor for increased mortality (adjusted hazard ratio [AHR] 2.93 95%
CI 2.22–3.85 p<0.001) and graft loss (AHR 1.85 95% CI 1.29–2.64) even after
consideration of cardiac and other complications.13 This highlights the importance of
clinically addressing UTI, whether early or late, in the course of kidney transplantation.
In addition, an increased number of UTIs over time may also be associated with chronic
rejection and renal scarring.14,15
2. What is the effective antibiotic prophylaxis for post–kidney transplant

patients to reduce the risk for UTI?
Oral TMP-SMX (160 mg/800 mg) taken twice daily immediately post-
transplant, then once daily as soon as the catheter is removed or the
patient is discharged, continued until six months post-transplantation,
reduces the risk of bacteriuria and bacteremia in post–renal transplant
recipients.
Summary of Evidence
A meta-analysis by Green et al. in 2011, which included six randomized
controlled trials (n=545) comparing antibiotic prophylaxis with other interventions
beginning postoperatively and continued for at least one month during the first six
months post-transplantation, showed that antibiotic prophylaxis decreased the risk of
developing bacteriuria (RR 0.41 95% CI 0.31–0.56; three trials) and bacteremia (RR
0.13 95% CI 0.02–0.7); however, it did not affect graft function or patient mortality. 16
Two studies included in the meta-analysis by Green et al. compared the
effects of high-dose and low-dose TMP-SMX. One study was a prospective randomized
double-blind study involving 132 patients, and it confirmed that TMP-SMX 320 mg/1600
mg every day during hospitalization was highly effective in preventing UTI, but a dose
of 160 mg/800 mg was effective only if the foley catheter was removed. Prophylaxis did
not prevent catheter-associated UTI in the early post-transplant period, but it decreased
the probability of UTI threefold (p<0.001) after catheter removal.17 The other study was
double-blinded, but the allocation generation and concealment processes were less
clearly described. High-dose TMP-SMX seems to be consistently more favorable than
low dose, with bacteriuria occurring less frequently in the former than in the latter (25%
vs. 50%, respectively).18
A recent retrospective cross-sectional study looked into the benefit of adding
one month of daily 250 mg ciprofloxacin (taken twice a day) after a six-month course of
TMP-SMX (taken daily for the first month then three times weekly for the next 5 months).
At one year follow-up, the ciprofloxacin group showed fewer UTI occurrences (23.6%
vs. 10.8%, p=0.01) and a shorter mean time to the first UTI (96.6±79.5 vs. 168±89.7
111
days, p=0.01).19 This study, however, is limited by several issues, including the
following:
There are recall, selection and other biases inherent to the nature of the study
design.
The (low) dose of TMP-SMX used in the study has been found to be inferior
compared to the standard recommended dose (160 mg/800 mg twice daily)
based on previous randomized trials of sound methodologic quality.
While the resistance patterns of the uropathogens isolated from those who
developed UTI within the one-year post-transplant period were similar
between the two treatment groups, there is no similar information for those
that occur beyond the follow-up period (after one year).
The effectiveness of this regimen needs to be confirmed in a randomized
controlled trial. As monotherapies, one randomized study compared the use of
ciprofloxacin 250 mg daily vs. TMP-SMX 80 mg/400 mg, both taken for six months, as
prophylaxis for post-transplant UTI.20 Ciprofloxacin has been shown to be more
effective than TMP-SMX in the prevention of UTI (RR 0.89), and with fewer adverse
events.20 However, the use of ciprofloxacin as prophylaxis is not recommended for
several reasons: First, because ciprofloxacin has no activity against Pneumocystis sp.,
prophylactic monotherapy with ciprofloxacin resulted in a higher incidence of
Pneumocystis pneumonia (14% vs. 0%).20 Second, fluoroquinolone use has been
associated with collateral damage such as the development of drug resistance (ESBL-
production). Third, in a country where tuberculosis is highly endemic, it is prudent to
reserve ciprofloxacin as a second-line drug for multidrug-resistant tuberculosis.
The optimal duration of antimicrobial prophylaxis for post-transplant UTI has not
been well studied. Different trials have reported antimicrobial prophylaxis durations
ranging from four21,22 to six20,23 to eight-and-a-half months.17 The American Society of
Transplantation (AST) recommends that antimicrobial prophylaxis be given for three to
six months,12 while the Kidney Disease Improving Global Outcomes (KDIGO) and the
European Association of Urology (EAU) recommend prophylaxis for at least six
months.3,11 Currently, there are concerns on the increasing resistance to TMP-SMX. At
the NKTI, the incidences of TMP-SMX–resistant E. coli were as follows: 78% in 2009,
79% in 2010, and 85% in 2011. The incidences of ciprofloxacin-resistant E. coli were
as follows: 67.7% in 2009, 71.4% in 2010, and 70.8% in 2011. Despite its high
resistance rates, antibiotic prophylaxis with TMP-SMX is still recommended.
Newer interventions, such as perioperative intravesical application of antibiotic
solution after renal transplantation, have been looked into in one study. The intervention
seems to be beneficial (RR 0.51 95% CI 0.34–0.76), but the allocation generation,
concealment and blinding of the study were not clearly reported. More studies are
needed before a recommendation regarding this intervention can be made. 24
References
1. De Souza RM, Olsburgh J. Urinary tract infection in the renal transplant patient. Nat Clin Pract
Nephrol. 2008 May;4(5):252-64.
2. Muñoz P. Management of urinary tract infections and lymphocele in renal transplant recipients.
Clin Infect Dis. 2001 Jul 1;33 Suppl 1:S53-7.
3. Grabe M, Bjerklund-Johansen TE, Botto H, Çek M, Naber KG, Pickard RS, Tenke P,
Wagenlehner F, Wullt B. Guidelines on urological infections. European Association of Urology
website. 2013.
112
4. Cuvelier R, Pirson Y, Alexandre G, van Ypersele de Strihou C. Late urinary tract infection after
transplantation: prevalence, predisposition and morbidity. Nephron. 1985;40(1):76-8.
5. Hamshere RJ, Chisholm GD, Shackman R. Late urinary-tract infection after renal transplantation.
Lancet. 1974;2(7884):793-4.
6. Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a
retrospective review at two US transplant centers. Clin Transplant. 2005 Apr;19(2):230-5.
7. Pellé G, Vimont S, Levy PP, Hertig A, Ouali N, Chassin C, Arlet G, Rondeau E, Vandewalle A.
Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. Am J
Transplant. 2007 Apr;7(4):899-907.
8. Iqbal T, Naqvi R, Akhter SF. Frequency of urinary tract infection in renal transplant recipients and
effect on graft function. J Pak Med Assoc. 2010;60(10):826-9.
9. Giral M, Pascuariello G, Karam G, Hourmant M, Cantarovich D, Dantal J, Blancho G, Coupel S,
Josien R, Daguin P, Méchineau S, Soulillou JP. Acute graft pyelonephritis and long-term kidney
allograft outcome. Kidney Int. 2002 May;61(5):1880-6.
10. Kamath NS, John GT, Neelakantan N, Kirubakaran MG, Jacob CK. Acute graft pyelonephritis
following renal transplantation. Transpl Infect Dis. 2006 Sep;8(3):140-7.
11. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical
practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl
3:S1-155.
12. Rice JC, Safdar N; AST Infectious Diseases Community of Practice. Urinary tract infections in
solid organ transplant recipients. Am J Transplant. 2009 Dec;9 Suppl 4:S267-72.
13. Abbott KC, Swanson SJ, Richter ER, Bohen EM, Agodoa LY, Peters TG, Barbour G, Lipnick
R, Cruess DF. Late urinary tract infection after renal transplantation in the United States. Am J
Kidney Dis. 2004 Aug;44(2):353-62.
14. Müller V, Becker G, Delfs M, Albrecht KH, Philipp T, Heemann U. Do urinary tract infections
trigger chronic kidney transplant rejection in man? J Urol. 1998 Jun;159(6):1826-9.
15. Dupont PJ, Psimenou E, Lord R, Buscombe JR, Hilson AJ, Sweny P. Late recurrent urinary
tract infections may produce renal allograft scarring even in the absence of symptoms or
vesicoureteric reflux. Transplantation. 2007 Aug;84:351-5.
16. Green H, Rahamimov R, Gafter U, Leibovitci L, Paul M. Antibiotic prophylaxis for urinary tract
infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect
Dis. 2011 Oct;13(5):441-7.
17. Fox BC, Sollinger HW, Belzer FO, Maki DG. A prospective, randomized, double-blind study of
trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical
efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-
benefit of prophylaxis. Am J Med. 1990 Sep;89(3):255-74.
18. Khosroshahi HT, Mogaddam AN, Shoja MM. Efficacy of high-dose trimethoprim-
sulfamethoxazol prophylaxis on early urinary tract infection after renal transplantation. Transplant
Proc. 2006 Sep;38(7):2062-4.
19. Wojciechowski D, Chandran S. Effect of ciprofloxacin combined with sulfamethoxazole-
trimethoprim prophylaxis on the incidence of urinary tract infections after kidney transplantation.
Transplantation. 2013 Aug 27;96(4):400-5.
20. Hibberd PL, Tolkoff-Rubin NE, Doran M, Delvecchio A, Cosimi AB, Delmonico FL, Auchincloss
H Jr, Rubin RH. Trimethoprim-sulfamethoxazole compared with ciproloxacin for the prevention
of urinary tract infection in renal transplant recipients. A double-blind, randomized controlled trial.
Online J Curr Clin Trials. 1992;Doc No 15.
21. Tolkoff-Rubin NE, Cosimi AB, Russell PS, Rubin RH. A controlled study of trimethoprim-
sulfamethoxazole prophylaxis of urinary tract infection in renal transplant recipients. Rev Infect
Dis. 1982;4(2):614-8.
22. Maddux MS, Veremis SA, Bauma WD, Pollak R, Mozes MF. Effective prophylaxis of early post-
transplant urinary tract infections (UTI) in the cyclosporine (CSA) era [Abstract]. Transplant Proc.
1989;21(1 Pt 2):2108-9.
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23. Moysés Neto M, Costa RS, Reis MA, Ferraz AS, Saber LT, Batista ME, Muglia V, Garcia TM,
Figueiredo JF. Use of ciprofloxacin as a prophylactic agent in urinary tract infections in renal
transplant recipients. Clin Transplant. 1997;11(5 Pt 1):446-52.
24. Salehipour M, Salahi H, Fathikalajahi A, Mohammadian R, Emadmarvasti V, Bahador A,
Nikeghbalian S, Kazemi K, Dehghani M, Malek-Hosseini SA. Is perioperative intravesically
applied antibiotic solution effective in the prophylaxis of urinary tract infections after renal
transplantation? Urol Int. 2010;85(1):66-9.
114
UTI prophylaxis for urologic procedures
Perioperative Antibiotic Prophylaxis for Patients Who Will Undergo Urologic

Procedures
1. Should patients who will undergo urologic procedures receive
perioperative prophylactic antibiotics?
Selected patients should receive perioperative prophylactic antibiotics

to prevent the occurrence of healthcare-associated infections arising
from diagnostic and therapeutic urologic procedures. These patients
include the following:
Patient Group Strength of Quality of

Men who will undergo transrectal or transperineal Strong High
prostate biopsy
Men who will undergo transurethral resection of Strong High
the prostate (TURP)
Patients who will undergo clean, contaminated, Strong Low
open or laparoscopic urological surgeries such as
pelvioureteric junction repair, nephron-sparing
tumor resection, total prostatectomy, bladder
surgery, partial cystectomy, urine diversion,
orthotopic bladder replacement or ileal conduit
Patients who will undergo complicated Strong Low
endourological surgery and shockwave
lithotripsy, nephrostomy tube insertion,
ureteroscopy of proximal or impacted stone, or
percutaneous stone extraction
For other procedures, the decision to give perioperative prophylactic

antibiotics will depend on the presence of risk factors for infectious
complications, such as old age, deficient nutritional status, impaired
immune response, diabetes mellitus, smoking, extreme weight,
coexisting infection at a remote site, lack of control of risk factors, long
preoperative hospital stay or recent hospitalization, history of recurrent
urogenital infections, surgery involving bowel segment, colonization of
microorganisms, long-term drainage, urinary obstruction or urinary
stone.
2. What is the approach to giving perioperative antibiotic prophylaxis in a

patient who will undergo a urologic procedure?
2.1 For patients who will undergo emergency urologic procedures, a

single dose of intravenous (IV) amikacin or ertapenem one hour
prior to the procedure is recommended.
115
2.2 Urine for Gram stain/culture and sensitivity (GS/CS) and blood
sample for serum creatinine should ideally be obtained prior to the
procedure and before the administration of amikacin.
2.3 For elective cases, do urine GS/CS prior to the procedure. If culture
is positive, then treat as asymptomatic bacteriuria (ASB; see
chapter on ASB) and start antibiotic therapy based on sensitivity
results. If culture is negative, start prophylactic antibiotics if the
patient will undergo TURP or transrectal or transperineal biopsy of
the prostate, or if there are risk factors for infectious complications
after the urologic procedure.
2.4 The duration of perioperative prophylaxis should be kept to a

minimum. The decision on whether to continue or shift antibiotics
and the duration after the procedure will depend on the best clinical
judgment of the physician.
3. What antibiotics can be used for perioperative prophylaxis for patients

who will undergo urologic procedures?
3.1 Amikacin 15 mg/kg or ceftriaxone 2 g IV single dose, one hour

before the procedure, are the recommended antibiotics for
perioperative prophylaxis prior to a urologic procedure.
In settings where resistance rates to cephalosporins and

quinolones are high, aztreonam 1 gram IV may be given one hour
before the procedure.
3.2 For patients who will undergo transrectal or transperineal prostate

biopsy, ciprofloxacin 500 mg administered orally (PO) 12 hours
prior to biopsy and repeated 12 hours after the first dose or
ciprofloxacin 400 mg IV via one-hour infusion two hours prior to the
procedure are acceptable options, provided resistance is not a
concern.
3.3 Metronidazole 500 mg IV single dose one hour prior to the

procedure is added for patients who will undergo urologic
procedures with manipulation of the bowel segments.
116
DISCUSSION
1. Should patients who will undergo urologic procedures receive
perioperative prophylactic antibiotics?
Selected patients should receive perioperative prophylactic antibiotics

to prevent the occurrence of healthcare-associated infections arising
from diagnostic and therapeutic urologic procedures. These patients
include the following:
Patient Group Strength of Quality of

Men who will undergo transrectal or transperineal Strong High
prostate biopsy
Men who will undergo transurethral resection of the Strong High
prostate (TURP)
Patients who will undergo clean, contaminated, open Strong Low
or laparoscopic urological surgeries such as
pelvioureteric junction repair, nephron-sparing tumor
resection, total prostatectomy, bladder surgery,
partial cystectomy, urine diversion, orthotopic
bladder replacement or ileal conduit
Patients who will undergo complicated Strong Low
endourological surgery and shockwave lithotripsy,
nephrostomy tube insertion, ureteroscopy of
proximal or impacted stone, or percutaneous stone
extraction
For other procedures, the decision to give perioperative prophylactic

antibiotics will depend on the presence of risk factors for infectious
complications, such as old age, deficient nutritional status, impaired immune
response, diabetes mellitus, smoking, extreme weight, coexisting infection at a
remote site, lack of control of risk factors, long preoperative hospital stay or
recent hospitalization, history of recurrent urogenital infections, surgery
involving bowel segment, colonization of microorganisms, long-term drainage,
urinary obstruction or urinary stone.
Summary of Evidence
The goal of perioperative antibiotic prophylaxis is to prevent healthcare-
associated infections arising from diagnostic and therapeutic procedures. Perioperative
antibiotic prophylaxis has been controversial especially with the lack of good studies to
support its use.1,2 Among the various urologic procedures, the use of perioperative
antibiotic prophylaxis is well documented only in transurethral resection of prostate and
prostate biopsy.
Three systematic reviews have consistently reported the benefit of
prophylaxis—the short course (<72 hours) regimen, in particular—in decreasing the
incidence of postoperative bacteriuria (from 26% to 9%) and other related complications
(e.g., fever, sepsis).3-5 On the other hand, at least six randomized trials included in a
systematic review have shown the benefit of prophylaxis in decreasing the incidence of
117
post-transrectal or transperineal core biopsy bacteriuria, although there has been no

conclusive evidence on its effect on the development of subsequent symptomatic
urinary tract infections (UTI).5 Table 18 summarizes the evidence in the use of
prophylaxis after various urological procedures. In coming up with the
recommendations on the use of prophylaxis for each of these procedures, it is very
important to consider three factors, keeping in mind that not all procedures are alike:
(1) the level of invasiveness of the procedure, (2) the risk for infectious complication of
the procedure (incidence of post-treatment bacteriuria or symptomatic UTI) and (3) the
overall clinical status of the patient. 1
Most of the trials have failed to consider the presence of risk factors that might
render patients more prone to developing postoperative complications. The presence
of these factors is a reason to administer antibiotic prophylaxis or prolong its duration
in an otherwise low-risk urological procedure due to the vulnerability of this set of
patients.
2. What is the approach to giving perioperative antibiotic prophylaxis in a

patient who will undergo a urologic procedure?
2.1 For patients who will undergo emergency urologic procedures, a

single dose of intravenous (IV) amikacin or ertapenem one hour
prior to the procedure is recommended.
2.2 Urine for Gram stain/culture and sensitivity (GS/CS) and blood
sample for serum creatinine should ideally be obtained prior to the
procedure and before the administration of antibiotic.
2.3 For elective cases, do urine GS/CS prior to the procedure. If culture
is positive, then treat as asymptomatic bacteriuria (ASB; see
chapter on ASB) and start antibiotic therapy based on sensitivity
results. If culture is negative, start prophylactic antibiotics if the
patient will undergo TURP or transrectal or transperineal biopsy of
the prostate, or if there are risk factors for infectious complications
after the urologic procedure (Table 19).
2.4 The duration of perioperative prophylaxis should be kept to a

minimum. The decision on whether to continue or shift antibiotics
and the duration after the procedure will depend on the best clinical
judgment of the physician.
118
Table 18. Summary of evidence on the use of prophylaxis in urologic procedures

Procedure Recommendation Evidence
Cystoscopy Low quality A systematic review of four randomized
evidence for the controlled trials (RCT) had conflicting
use of prophylaxis results—two showed a decrease in the
incidence of bacteriuria and symptomatic UTI
with antibiotic prophylaxis, while the other
two showed no decrease5
There is low incidence of bacteriuria and
symptomatic UTI after cystoscopy6,7
Urodynamic Low quality Five studies with poor methodologic quality5
investigation evidence for the There is low incidence of bacteriuria and
use of prophylaxis symptomatic UTI after urodynamic studies1
Transurethral Moderate quality Two RCTs, which compared antibiotic
resection of bladder evidence against prophylaxis with either placebo or no
tumor (TURB) the use of treatment, reported no significant difference
prophylaxis in the rates of post-TURB bacteriuria
between treatment groups8,9
No incidence of post-TURB symptomatic UTI
in either group9
Extracorporeal Moderate quality Only one of 4 RCTs showed significant
shockwave evidence against benefit with antibiotic prophylaxis.10
lithotripsy (ESWL) the use of Antibiotics used were ciprofloxacin,
prophylaxis ofloxacin, ceftriaxone, and
amoxicillin/clavulanic acid5
Post-ESWL symptomatic UTI rates were
similarly low between treatment groups5
A meta-analysis of nine RCTs showed no
benefit with the use of prophylaxis in terms of
fever (RR 0.36, 95% CI 0.07 to 2.36), urine
culture positivity (RR 0.77, 95% CI 0.54 to
1.11), and incidence of UTI (RR 0.54, 95%
CI 0.29 to 1.01)11
Endoscopic removal Moderate quality For therapeutic ureterorenoscopy such as
of stones (via evidence for the endoscopic removal of stones, two RCTs12,13
ureterorenoscopy) use of prophylaxis reported reductions in bacteriuria
postoperatively with prophylaxis, but results
reached significance only in one RCT (12.5%
to 1.8%, n=113)12
No studies on diagnostic ureterorenoscopy
alone
Percutaneous Low quality Small observational studies reported a
nephrolithotomy evidence for the reduction in postoperative fever and
use of prophylaxis symptomatic UTI
One RCT included in the review by Bootsma
et al reported a reduction in bacteriuria with
antibiotic prophylaxis (bacteriuria: 12% in the
placebo group, 5% in the prophylaxis group)
but this was not statistically significant13
Clean, contaminated Low quality No direct studies available
or open/laparoscopic evidence for the Clean-contaminated procedures (opening of
urologic use of prophylaxis the urinary tract) may warrant prophylaxis1
interventions such
119
as pelvioureteric Based on general surgery studies, clean

junction repair, wounds do not warrant prophylaxis, while
nephron-sparing contaminated and dirty urological surgeries
tumor resection, should receive therapeutic antibiotics and not
total prostatectomy, prophylactic antibiotics1,5
bladder surgery,
partial cystectomy,
urine diversion,
orthotopic bladder
replacement, ileal
conduit
Table 19. Generally accepted risk factors for infectious complication

General risk factors Special risk factors associated with an increased
bacterial load
Older age Long preoperative hospital stay or recent
hospitalization, complicated
Deficient nutritional status History of recurrent urogenital infections
Impaired immune response Surgery involving bowel segment
Diabetes mellitus Colonization with microorganisms
Smoking Long-term drainage
Extreme weight Urinary obstruction
Coexisting infection at a remote site Urinary stone
Lack of control of risk factors
Adapted from Grabe et al.
Summary of Evidence
The goal of antibiotic prophylaxis is to prevent procedure-related infections.
However, this should not be done at the expense of promoting bacterial resistance,
increasing the risk for Clostridium difficile–associated diarrhea or incurring unnecessary
cost for the patient.14 A careful assessment of the patient and the individual clinical
context is necessary to come up with the optimal prophylactic regimen. Timing of
administration is very important in allowing the antibiotic to reach effective
concentrations at the time of highest risk during the procedure. 1 The antibiotic
prophylaxis should be given within one hour of the surgical incision (except
fluoroquinolones and vancomycin, which may require 120 minutes) 1,14
In emergency situations where a patient has to undergo immediate urologic
procedures, a single dose of IV amikacin or ertapenem one hour prior to the procedure
is recommended. Urine for GS/CS and blood sample for serum creatinine (for dose
adjustment) should ideally be obtained prior to the procedure and before the
administration of antibiotic. If this is not possible, a sample should be obtained during
the procedure. Tailor the antibiotics once the culture results are available.
For elective cases, a urine sample should be sent for GS/CS prior to the
procedure. If the pre-procedure culture is positive, then treat the patient as ASB if the
patient will undergo urological procedures (see chapter on ASB) and start antibiotic
treatment based on sensitivity results. It is recommended that urine culture be repeated
48–72 hours after the initial antibiotic dose. If the urine has been rendered sterile, one
may proceed with the contemplated procedure. However, if the culture remains positive,
one may proceed with the procedure but shift the antibiotic regimen to one that the
isolate is susceptible to.
120
If the pre-procedure culture is negative, start prophylactic antibiotics for

selected patients whose situations were discussed in the preceding section (i.e.,
undergoing TURP or transrectal or transperineal biopsy of the prostate, or with risk
factors for infectious complications after the urologic procedure).
The decision to continue or shift antibiotics and the duration after the
procedure will depend on the best clinical judgment of the physician. Perioperative
prophylaxis should be kept to a minimum; it can be given as a single dose in most
cases, or at least discontinued within 24 hours after the procedure. 14 Previously
published guidelines suggest that antimicrobial prophylaxis is unnecessary after wound
closure or upon termination of an endoscopic procedure, but these are based on low-
quality evidence, i.e., expert opinion or extension of recommendations from general
surgery studies.14-16 A longer duration of antibiotic prophylaxis is frequently considered
when there are significant risk factors for infectious complications; the presence of
prosthetic material; in the presence of infection, for which a therapeutic regimen rather
than prophylaxis is needed; and when an indwelling tube is manipulated. 1,14
3. What antibiotics can be used for perioperative prophylaxis for patients

who will undergo urologic procedures?
3.1 Amikacin 15 mg/kg or ceftriaxone 2 g IV single dose, one hour
before the procedure, are the recommended antibiotics for
perioperative prophylaxis prior to a urologic procedure.
In settings where resistance to cephalosporins and quinolone
is high, aztreonam one gram IV may be given one hour before the
procedure.
3.2 For patients who will undergo transrectal or transperineal prostate
biopsy, ciprofloxacin 500 mg administered orally (PO) 12 hours
prior to biopsy and repeated 12 hours after the first dose or
ciprofloxacin 400 mg IV via one-hour infusion two hours prior to the
procedure are acceptable options, provided resistance is not a
concern.
3.3 Metronidazole 500 mg IV single dose one hour prior to the
procedure is added for patients who will undergo urologic
procedures with manipulation of the bowel segments.
Summary of Evidence
There are general guidelines in choosing the most appropriate prophylactic
antibiotic for urological procedures, taking into account both the surgical site and the
properties of the antimicrobial agent. The agent to be used should be effective against
the most common pathogens that cause disease in the operative site. The most
common pathogens that cause postoperative infections include the
Enterobacteriaceae, Enterococci and Staphylococci. 1 A local prospective surveillance
study conducted at the Philippine General Hospital reported that among 116 patients
with prolonged indwelling urinary catheters, the most common isolates were E. coli
(30%), Enterobacter spp. (22%) and Pseudomonas aeruginosa (9.7%).17 There were
overall high resistance rates to ampicillin (92.14%), ciprofloxacin (80.7%) and
121
cotrimoxazole (80%). Resistance rate to meropenem was low at 6.43%. These

resistance patterns are consistent with the Philippine Antimicrobial Resistance
Surveillance Program (ARSP) 2015 Data Summary Report. According to the ARSP,
urinary E. coli isolated from inpatients had the lowest resistance rates to the non-anti-
Pseudomonal carbapenem ertapenem (5.7%, n=1241) and amikacin (4.2%, n=2105).
Resistance rates to cotrimoxazole (68%) and ampicillin (84%) remain very high.
Resistance rates to ceftriaxone (40%, n=1973) and ciprofloxacin (43%, n=2096)
continue to increase.18 The resistance rates of Klebsiella pneumoniae are similar with
E. coli.18 Another prospective cohort study of patients diagnosed with complicated UTI
(with catheter-associated UTI as the most common underlying condition, 80%) in two
training hospitals in Metro Manila reports similar trends. 19 Sensitivity to meropenem,
ertapenem and amikacin remained high at 87%, 76% and 82%, respectively.
Certain drug characteristics should be considered when choosing a
prophylactic antibiotic. The drug should be able to reach therapeutic concentrations at
the operative site and have adequately long half-life to maintain sufficient serum and
tissue concentrations for the entire length of the procedure, thus minimizing the need
for another dose. Cephalosporins (such as ceftriaxone), fluoroquinolones (such as
ciprofloxacin) and aminoglycosides (amikacin) achieve good concentrations in the
urinary tract, are generally efficacious, have long half-lives, and are relatively
inexpensive.1,20 Lastly, the antibiotic should be safe, cost-effective and cause no
collateral damage to the patient and the environmental flora. 14
Amikacin (15 mg/kg) or ceftriaxone (2 g IV single dose) one hour before the
procedure is the recommended antibiotics for perioperative prophylaxis, considering
these two drugs’ good concentrations at the urogenital tract, adequate coverage for
the most common uropathogens and long half-lives. Caution should always be taken
when giving aminoglycosides to patients with renal insufficiency. Baseline and
subsequent serum creatinine determinations may be prudent for monitoring kidney
function.
For patients who will undergo transrectal or transperineal prostate biopsy,
ciprofloxacin 500 mg PO 12 hours prior to biopsy and repeated 12 hours after the first
dose or ciprofloxacin 400 mg IV one-hour infusion two hours prior to the procedure are
acceptable options because fluoroquinolones achieve high levels of concentration in
the prostate,21 and with their good oral bioavailability, they can be conveniently given
per orem on an outpatient basis.
Metronidazole 500 mg IV single dose one hour prior to the procedure is added
for patients who will undergo urologic procedures with manipulation of the bowel
segments because anaerobes are possible pathogens that may cause subsequent
infections. Although they have the least resistance rates, carbapenems (e.g.,
meropenem, ertapenem) are reserved for high-risk patients with clear evidence of
infection, to avoid selection pressure and the emergence of resistance against these
broad-spectrum agents.
References
1. Grabe M, Bjerklund-Johansen TE, Botto H, Çek M, Naber KG, Pickard RS, Tenke P, Wagenlehner
F, Wullt B. Guidelines on urological infections. Limited update March 2013. European Association
of Urology; 2013.
122
2. Çek M, Tandoğdu Z, Naber K, Tenke P, Wagenlehner F, van Oostrum E, Kristensen B, Bjerklund

Johansen TE; Global Prevalence Study of Infections in Urology Investigators. Antibiotic prophylaxis
in urology departments, 2005-2010. Eur Urol. 2013 Feb;63(2):386-94.
3. Berry A, Barratt A. Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis. J
Urol. 2002;167(2 Pt 1):571-7.
4. Qiang W, Jianchen W, MacDonald R, Monga M, Wilt TJ. Antibiotic prophylaxis for transurethral
prostatic resection in men with preoperative urine containing less than 100,000 bacteria per ml: a
systematic review. J Urol. 2005;173(4):1175-81.
5. Bootsma AM, Laguna Pes MP, Geerlings SE, Goossens A. Antibiotic prophylaxis in urologic
procedures: a systematic review. Eur Urol. 2008 Dec;54(6):1270-86.
6. Almallah YZ, Rennie CD, Stone J, Lancashire MJ. Urinary tract infection and patient satisfaction
after flexible cystoscopy and urodynamic evaluation. Urology. 2000;56(1):37-9.
7. Clark KR, Higgs MJ. Urinary infection following out-patient flexible cystoscopy. Br J Urol.
1990;66(5):503-5.
8. Delavierre D, Huiban B, Fournier G, Le Gall G, Tande D, Mangin P. The value of antibiotic
prophylaxis in transurethral resection of bladder tumors. Apropos of 61 cases. Prog Urol.
1993;3(4):577-82.
9. McDermott JP, Ewing RE, Somerville JF, Gray BK. Cephradine prophylaxis in transurethral
procedures for carcinoma of the bladder. Br J Urol. 1988;62(2):136-9.
10. Claes H, Vandeursen R, Baert L. Amoxycillin/clavulanate prophylaxis for extracorporeal shock wave
lithotripsy—a comparative study. J Antimicrob Chemother. 1989;24 Suppl B:217-20.
11. Lu Y, Tianyong F, Ping H, Liangren L, Haichao Y, Qiang W. Antibiotic prophylaxis for shock wave
lithotripsy in patients with sterile urine before treatment may be unnecessary: a systematic review
and meta-analysis. J Urol. 2012;188(2):441-8.
12. Knopf HJ, Graff HJ, Schulze H. Perioperative antibiotic prophylaxis in ureteroscopic stone removal.
Eur Urol. 2003;44(1):115-8.
13. Fourcade RO. Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract
stones: a randomized study. The Cefotaxime Cooperative Group. J Antimicrob Chemother. 1990;26
Suppl A:77-83.
14. Wolf JS, Bennett CJ, Dmochowski RR, Hollenbeck BK, Pearle MS, Schaeffer AJ; Urologic Surgery
Antimicrobial Prophylaxis Best Practice Policy Panel. Best practice policy statement on urologic
surgery antimicrobial prophylaxis. Sep 2008 ed. American Urological Association Education and
Research Inc.; 2008.
15. Bratzler DW, Houck PM; Surgical Infection Prevention Guideline Writers Workgroup. Antimicrobial
prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention
Project. Am J Surg. 2005;189(4):395-404.
16. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site
infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp
Epidemiol. 1999;20(4):250-78.
17. Matias PJ, Lapitan MC. The bacteriology of urine in urologic patients with prolonged indwelling
urinary catheters in the Philippine General Hospital. Phil J Urol. 2012;22(2):51-7.
18. Antimicrobial Resistance Surveillance Reference Laboratory. Antimicrobial resistance surveillance
program 2012 data summary report. Manila: Department of Health, Research Institute for Tropical
Medicine, Antimicrobial Resistance Surveillance Program; 2012.
19. Henson K, Gamponia K, Zamora R, Alejandria M, Saniel M, Destura R. Prevalence and risk factors
for extended spectrum beta-lactamase producing organisms among patients with complicated
urinary tract infections.
20. Amsden GW, Ballow CH, Bertinojr JS, Kashuba AD. Pharmacokinetics and pharmacodynamics on
anti-infective agents. In: Mandell GL, Bennett JC, Dolin R, eds. Mandell, Douglas, and Bennett’s
principles and practice of infectious diseases. Vol. 1. 7th ed. Philadelphia, PA: Elsevier; 2005.
21. Wagenlehner FM, Naber KG. Fluoroquinolone antimicrobial agents in the treatment of prostatitis
and recurrent urinary tract infections in men. Curr Prostate Rep. 2004;2(2):96-103.
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Urinary candidiasis
SPECIFIC ISSUES OF CONCERN IN COMPLICATED URINARY TRACT

INFECTION
URINARY CANDIDIASIS
1. What is candiduria, and what is its clinical significance?
Candiduria is defined as the presence of Candida species regardless of colony

count in properly collected urine specimens taken on two separate occasions at
least two days apart. The presence of candiduria may represent a whole
spectrum of pathologic states, from invasive renal parenchymal disease, fungal
balls in obstructed ureters and lower urinary tract infection (UTI), to benign
conditions such as colonization.
2. What is the significance of yeast cells or hyphae on urine microscopy?

What is the role of pyuria in the diagnosis of urinary candidiasis?
The presence of yeast cells or hyphae on microscopy, especially when

there is pyuria, may be a clue that a fungal infection is present. However,
these findings should be correlated clinically.
3. If antimicrobial therapy is deemed necessary for a patient with candiduria,

what antifungal agents are effective for treatment?
3.1 The first line of treatment is fluconazole 400 mg loading dose, and
then 200 mg/day for 7–14 days. The route of administration depends on
patient status and oral tolerability.
3.2 In certain clinical situations such as prior azole use, refractory

infection or suspicion of drug resistance to fluconazole (e.g., patients
with suspected C. glabrata infection), IV amphotericin B deoxycholate
(AmBd) at a dose of 0.3–1.0 mg/kg per day can be given.
3.3 For patients who will undergo urologic procedures and in whom
candiduria was found to be present, fluconazole 200–400 mg (3–6
mg/kg) daily or AmBd 0.3–0.6 mg/kg daily for several days before and
after the procedure is recommended.
124
Urinary candidiasis
4. What is the value of bladder irrigation in the management of urinary

candidiasis?
Bladder irrigation with amphotericin B can be used as an adjunct therapy

to systemic antifungal agents in the treatment of refractory cystitis (e.g.,
infections from Candida with either acquired or inherent resistance to
azoles). When used, a continuous irrigation of amphotericin B at a
concentration of 50 mg per liter of sterile water for a period of five days is
recommended.
125
Urinary candidiasis
DISCUSSION
1. What is candiduria, and what is its clinical significance?
Candiduria is defined as the presence of Candida species regardless of

colony count in properly collected urine specimens taken on two separate
occasions at least two days apart. The presence of candiduria may
represent a whole spectrum of pathologic states, from invasive renal
parenchymal disease, fungal balls in obstructed ureters and lower urinary
tract infection (UTI), to benign conditions such as colonization.
Summary of Evidence
There is no consensus on the definition of significant candiduria. Colony
counts of >104 cfu/ml of Candida species have been associated with infection in patients
without indwelling urinary catheters. 1 In other studies, clinically significant renal
candidiasis has been reported with lower colony counts of 10 3/ml of urine.2,3 Indeed,
colony counts were not predictive of significant infection or upper tract involvement as
reported in a prospective case-control study conducted in a local tertiary hospital
involving 55 patients with positive urine cultures for Candida spp. The study was not
able to find a level of colony count that could be associated with the presence or
absence of fever, candidemia, relapse of candiduria and death (using Fisher's exact
test).4 The level of colony count was also not predictive of disease severity. Candidemia
and sepsis can occur even in low colony counts, and high colony counts will not
necessarily mean a more severe disease. 4
Significant candiduria should also be differentiated from contamination and
colonization. Contamination may result from the improper collection of urine specimens,
especially in catheterized patients or in women with Candida in the perineum.
Colonization, on the other hand, may involve the presence of Candida spp. on drainage
catheters or other foreign bodies in the urinary tract. Both contamination and
colonization can lead to increased colony counts in urine cultures. A second sterile urine
examination, taken either after changing the urinary catheter or via clean catch, would
be needed to better identify whether the increased colony count is due to infection or
simply due to colonization or contamination. 5
Candida albicans remains the most common species isolated, followed by C. tropicalis
and C. glabrata, with prevalences ranging from 36–70%, 5–53% and 7–9%,
respectively.3,6-8 In a prospective multicenter surveillance study of funguria in
hospitalized patients, C. albicans was found in 52% of 861 patients with funguria,
followed by C. glabrata in 16%.9 In a retrospective study conducted in four tertiary
hospitals in Metro Manila from 1992–1993, the prevalence rate of candiduria was 6.4%,
with C. albicans accounting for 73% of the cases.7
2. What is the significance of yeast cells or hyphae on urine microscopy? What

is the role of pyuria in the diagnosis of urinary candidiasis?
The presence of yeast cells or hyphae on microscopy, especially when there

is pyuria, may be a clue that a fungal infection is present. However, these
findings should be correlated clinically.
126
Urinary candidiasis
Summary of Evidence
A gram stain of centrifuged urine showing yeasts may suggest fungal
infection. C. albicans, as well as other Candida species which are less common such
as C. parapsilosis and C. tropicalis may be seen as budding yeasts, 4–10 µm in
diameter and possibly with hyphal elements, under microscopy. 10
The absence of hyphae on microscopy, however, does not rule out Candida
infection. C. glabrata, which presents on microscopy as smaller budding yeasts (2–4
µm in diameter) without hyphal elements, can cause UTI.10 Additionally, it was noted in
an experimental murine model that some non-hyphae-forming C. albicans variants can
also cause UTI.11
Most patients with urinary catheters have pyuria in the urine as a nonspecific
findin caused by the mechanical sloughing of the bladder mucosa by the catheter. 12 In
patients without a urinary catheter, pyuria and the presence of yeasts, as well as the
absence of bacterial growth, may point towards a Candida infection.10
On the other hand, the absence of pyuria on urine microscopy and low colony
counts on urine culture may help rule out a Candida infection.12 It is always prudent,
however, to interpret these results in the proper clinical context, given their low
diagnostic sensitivities and the absence of correlation with disease severity. 4,12
3. What are the clinical presentations of candiduria, and when is treatment

required?
See Table 19.
Summary of Evidence
Candiduria may have various clinical manifestations. Some patients may
present with no symptoms, while others may be desperately ill. Fisher et al 13 put forward
a classification scheme that may be useful in identifying which patients would require
treatment. Fisher et al suggested that patients with candiduria be classified into five
groups: (1) patients with asymptomatic candiduria who were previously healthy; (2)
patients with asymptomatic candiduria who have predisposing factors and are being
treated as outpatients; (3) patients with asymptomatic candiduria with predisposing
factors who are being treated as inpatients; (4) patients with symptomatic candiduria
(this includes patients with cystitis, pyelonephritis, urinary tract fungus balls, etc.); and
(5) clinically unstable patients with candiduria.
Asymptomatic candiduria in previously healthy patients

Because contamination is not unusual, especially among female patients,
whose vaginal area is normally inhabited by many organisms, a repeat urine culture
should be performed to verify the presence of candiduria.8,13,14 Once candiduria is
confirmed, possible predisposing factors (Table 20) should be investigated through
careful history-taking, physical examination and screening laboratory tests. It is also
important to check for the possibility of a fungal genital mucositis in the glans or
vagina.12 In a previously healthy patient in whom no explanation for candiduria is found,
careful observation is generally all that is necessary. 8,13,14 In most individuals without
predisposing factors, candiduria is expected to resolve spontaneously in a matter of
weeks or months.13
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Urinary candidiasis
Table 19. Clinical presentations of candiduria

Clinical Patient Removal of Predisposing Strength of
Presentation of Characteristic Factor Recommendation,
Candiduria Level of Evidence
Asymptomatic No explanation for Careful observation Strong
candiduria candiduria found If repeat exam still grows recommendation,
(previously after extensive fungi, check for possible low quality of
healthy patient) clinical investigation fungal genital mucositis evidence
(vagina or glans)
Asymptomatic Predisposing factors No antifungal treatment Strong
and minimally that lead to the recommended recommendation,
symptomatic development of Modification of risk factors moderate quality of
patients candiduria are is the first-line approach evidence
(outpatients) present* (e.g., control of diabetes,
discontinuation of
antibiotics, or removal of
indwelling catheters and
other urinary tract
instruments**)
Asymptomatic Predisposing factors Consider the possibility of Weak
candiduria and for infectious disseminated candidiasis recommendation,
minimally complications are Modification of risk factors low quality of
symptomatic present* Give antifungal treatment evidence
patients for patients who will
(inpatients) undergo urologic
procedures
If necessary, do imaging
studies of the kidneys and
the urinary system to rule
out abscess, fungus ball or
other urologic
abnormalities
Symptomatic Candida cystitis or Modification of risk factors Strong
candiduria pyelonephritis, Start antifungal treatment recommendation,
fungus ball, those Surgical intervention, when low quality of
with solid evidence of necessary evidence
infection of the
kidney or collecting
system
Candiduria in ICU patients, Modification of risk factors Strong
clinically unstable suspected Start antifungal treatment recommendation,
patients disseminated low quality of
disease, neutropenic evidence
patients, septic
patients
*Predisposing factors include DM, renal transplantation, extremes of age, broad-spectrum antibiotic use,
instrumentation of the urinary tract, congenital or other structural abnormalities of the genitourinary tract,
urinary stasis and interruption of the flow of urine, chronic renal failure and hemodialysis, bladder
distension, nephrolithiasis, female sex, concomitant bacteriuria or genitourinary tuberculosis, prolonged
hospitalization, intensive care unit (ICU) admission, indwelling urinary tract devices, malignancy,
neutropenia and other immunosuppressed conditions, immunosuppressive therapy, prior surgery
(urological and non-urological)
** If complete removal of these instruments is not possible, replacement of the device with new ones is
still beneficial.
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Urinary candidiasis
Table 20. Predisposing factors for candiduria and Candida UTIs3,7,9,13,15-18

Diabetes mellitus
Extreme age
Broad-spectrum antibiotic use†
Instrumentation of the urinary tract
Chronic renal failure and hemodialysis
Female sex
Concomitant bacteriuria or genitourinary tuberculosis
Prolonged hospitalization
Congenital or other structural abnormalities of the genitourinary tract
ICU admission
Indwelling urinary tract devices
Malignancy
Neutropenia and other immunosuppressed conditions
Immunosuppressive therapy
Prior surgery (urological and non-urological)
Bladder distention
Urinary stasis and interruption of the flow of urine
Nephrolithiasis
† The strongest correlation is with the use of meropenem (r=0.79, p<0.001) and ceftazidime
(r=0.66, p=0.001).20
Asymptomatic candiduria in predisposed outpatients

Several studies have looked into the association of the most common risk
factors for candiduria and Candida UTI with the development of infectious
complications. In a case-control study, Harris19 analyzed the risk factors associated with
catheter-associated candiduria due to C. glabrata (40 cases) and C. albicans (289
cases). Multivariate analysis showed that female gender [RR 2.93 (1.23–6.99) p=0.12
for C. glabrata; RR 2.54(1.67–3.89) p<0.001 for C. albicans], diabetes [RR 3.50 (1.57–
7.83) p<0.01 for C. glabrata only], ICU admission [RR 3.14 (1.39–7.08) p<0.01 for C.
glabrata; RR 3.57 (2.32–5.48) p<0.001 for C. albicans] and previous antibiotic use [RR
10.64 (2.36–47.97) p<0.001 for C. glabrata; RR 3.87 (2.24–6.68) p<0.001 for C.
albicans] were strongly associated with candiduria from both species. It is interesting to
note that prior use of fluconazole [RR 4.37 (1.32–14.43) p<0.01] and quinolone [RR
3.16 (1.14–8.80) p<0.01] were specifically associated with candiduria due to C. glabrata
but not C. albicans.19
A similar prospective single-center case-control study involving 145 subjects
with candiduria was done in India. C. albicans was isolated in 23% of cases, while non-
albicans species were isolated in 71%, with C. tropicalis and C. glabrata as the
predominant species.15 Previous use of antibiotics (cephalosporin the most common)
was noted in 91–92% of patients with candiduria. Univariate logistic regression analysis
revealed the following factors to be associated with candiduria: hospital stay >10 days,
ICU stay >5 days prior to culture, concomitant or recent urinary bladder catheterization,
infections and antimicrobial use in the past, most recent plasma glucose >180 mg/dl
and serum albumin <3 g/L. After multivariate analysis, the following factors retained
significance of association (p≤0.05): recent antimicrobial use and plasma glucose >180
mg/dl. Significant association with death in candiduria (p≤0.05) was seen in the
following factors using univariate logistic regression analysis: the use of urinary
129
Urinary candidiasis
diversion devices, the use of more than two classes of antimicrobials, stay in the ICU,
and renal failure.15
Admission to the ICU was studied more closely in a prospective study that
identified possible predisposing factors to Candida UTI.3 The study reported that the
isolation rate of Candida spp. increased with the number of days a patient was admitted
at the ICU. Similar to earlier studies, statistically significant (p=0.001) higher Candida
isolation rates were observed among patients who have stayed in the ICU for over a
week than among those who have just been admitted. 3,21
The use of indwelling urinary catheters has been notoriously associated with
the development of catheter-associated UTI, with as much as 67% of candiduria
patients having indwelling foley catheters at the time of the event.3,18 One surveillance
study of nosocomial infections in medical ICUs further reported that C. albicans was
more commonly isolated in catheter-associated nosocomial UTIs than in non-catheter-
associated nosocomial infections (21% vs. 13%, p=0.009).22 UTI from all fungal
pathogens occurred more frequently in patients with catheters than in those without
(40% vs. 22%, p<0.001).22
Treatment of asymptomatic and minimally symptomatic candiduria is not
recommended because it does not provide clear clinical benefits such as long-term (i.e.,
more than two weeks) eradication of the fungi. A randomized multicenter placebo-
controlled study compared fungal eradication rates among 316 consecutive
asymptomatic/minimally symptomatic candiduria patients whose risk factors for
candiduria have been resolved and who had been given either fluconazole or placebo
for 14 days.23
Short-term rates of eradication of Candida species from the urine were higher
in patients who had received fluconazole therapy than those who did not (RR 1.7 95%
CI 1.27–2.26 p<0.001). However, sub-analysis for those patients who were able to
complete the recommended duration in both treatment groups showed that rates of
candiduria two weeks after discontinuation of therapy were similar in the fluconazole
and placebo groups (RR1.04 95% CI 0.84–1.23 p=0.7), and relapse rates were similar
as well (9% vs. 4%, p=0.6).23
Long- term eradication rates were not associated with clear clinical benefits
in the asymptomatic or minimally symptomatic population of predominantly elderly,
debilitated patients in this study. This trend is also seen in another study that compared
short-course antifungal regimens (fluconazole, IV amphotericin B and bladder irrigation
with amphotericin B) with just the removal of the predisposing factors.24
The rates of spontaneous clearance were significantly lower in the treatment
groups at day 1 post-treatment (40% vs. 58.6% vs. 55.2 vs. 82% for no treatment,
fluconazole, IV amphotericin B and bladder irrigation with amphotericin B, respectively)
but the rates tended to decrease at day 7. 24
In an observational study of 55 patients in a tertiary hospital in Manila, clinical
improvement was notably more common in cases where the catheter was removed.
Clinical improvement was significantly more common in patients whose catheters were
removed whether or not treatment was given (p<0.05). 4 The same study reported that
fatal infections were significantly more common in patients whose catheters were
retained compared with those whose catheters were removed (p<0.05). Clearly, for
patients with asymptomatic or minimally symptomatic candiduria in whom predisposing
factors are present, modification of these risk factors is the first-line approach and by
itself generally results in the spontaneous resolution of the candiduria. If complete
130
Urinary candidiasis
removal of these instruments is not possible, replacement of the device with a new one
is still beneficial.
Asymptomatic candiduria in predisposed inpatients

Despite candidemia being reported in <5% of patients in most ICUs, the
possibility of disseminated candidiasis should be considered in all hospitalized patients
with candiduria, especially among critically ill patients. 13 Candiduria is seen in as many
as 46%–80% of persons with candidemia and may be the first and the only
manifestation of disseminated or invasive candidiasis. 3,21,25,26
The modification of risk factors that predispose to Candida UTI is still the
recommended first-line strategy for this subset of patients. Changing or removing the
catheter is recommended. Discontinuing antibiotics that are no longer necessary and
treating other predisposing conditions simultaneously should also be done. In one
cross-sectional study involving chart review of 188 patients with candiduria, patients
were divided into two groups: group 1, patients who received any antifungal treatment;
and group 2, patients who never received any antifungal treatment. 6 It was surprising
to note that patients who received antifungal treatment were significantly more likely to
have positive follow-up cultures (average follow-up time of 18 months) compared to
those who did not (group 1: 23%, n=273; group 2: 7%, n=150; p<0.01). One limitation
of this study is that more cultures were likely to be obtained from treated patients,
thereby increasing the likelihood of positive follow-up cultures.6 Several randomized
control studies, despite having low- to moderate-quality assessments due to
imprecision, inadequate description of randomization and allocation procedures, and
indirectness (i.e., the included patients were not divided into clinical presentation
groups, e.g., asymptomatic in previously healthy, asymptomatic among inpatients, and
outpatients with risk factors and symptomatic candiduria), generally showed results
towards not initiating antifungal therapy.18,24,27 Based on these, it is recommended that
antifungal treatment of candiduria in a hospitalized inpatient should be reserved only
for those who have solid evidence of infection of the kidney or collecting system or
disseminated candidiasis.
If, after the removal of the predisposing factors, the candiduria still persists,
investigation for a more deep-seated infection should be done. Imaging studies of the
kidneys and collecting system may reveal renal abscess, fungus ball, or other urologic
abnormalities that may be responsible for the persistent funguria. 13,14
Treatment should also be considered as a prophylactic measure for patients
who are about to undergo invasive urologic procedures, to avoid the risk of developing
invasive candidiasis and candidemia.12,28
Symptomatic candiduria
Symptomatic candiduria can present as any of the following syndromes:
1. Cystitis
Candida cystitis may present with lower urinary signs and symptoms
such as dysuria, hematuria, urgency and suprapubic tenderness.5
2. Candida pyelonephritis
Candida pyelonephritis has a similar presentation to bacterial
pyelonephritis. It may also be associated with candidemia, sepsis and septic
shock.5 The infection usually occurs via the hematogenous route but can also
131
Urinary candidiasis
occur through ascending infection in cases of obstruction, concomitant

bacteriuria or immunosuppression.13
3. Fungus balls (bezoars and mycetomas) of the urinary tract

Reports of cases of fungus balls in the urinary tract are mostly from
the pediatric population, especially in neonates. 29-37 This was also found in
some reports of diabetic patients.38,39 However, there has been a case report
of two immunocompetent women with no known predisposing factors who
presented with Candida mycetomas in the renal pelvis, causing urinary tract
obstruction.40
On radiologic imaging, fungus balls may present as an intraluminal
filling defect of the drainage system, which may lead to obstruction. It is
important to note, however, that blood clots, radiolucent urinary calculi, air
bubbles, inflammatory debris and transitional cell carcinoma can present
similarly. On ultrasound, fungus balls commonly present as hyperechoic
lesions of the collecting system, but in some instances, they can also be
hypoechoic.40
Candiduria should be treated with appropriate antifungal agents in

symptomatic patients.8,12,14 Management of predisposing conditions should also be a
part of the therapeutic regimen. Patients may require surgical interventions such as
drainage or debridement in the case of abscesses; however, the decision to perform
these interventions will depend on individual patient contexts and scenarios. In the case
of Candida fungus ball, the location will determine the approach to therapy. 14 Systemic
treatment with amphotericin B or fluconazole has been used. The use of systemic
therapy is justifiable because fungus balls may have developed from systemic infection
or from deep seated parenchymal infection. However, aside from systemic therapy,
invasive procedures are also often necessary to remove the bulk of the mass and
relieve obstruction.8,13,14
Candiduria in clinically unstable patients

Candiduria should be treated with appropriate antifungal agents in critically ill
patients such as those admitted in the ICU, septic patients, those with neutropenia and
those with suspected disseminated disease. 8,13,14 Decreasing the burden of infection for
these patients at the earliest possible time may be lifesaving. At least two randomized
controlled studies, although limited by their methodologic quality and indirectness, have
demonstrated significantly higher short-term fungal clearance rates with antifungal
administration as early as day 1 post-treatment.23,24
For critically ill patients, candiduria, whether symptomatic or not, should
initially be regarded as a harbinger of disseminated candidiasis. 13 Since candiduria may
be a manifestation of life-threatening disseminated infection in critically ill patients in
some instances, it may require aggressive systemic antifungal treatment.3,26,41 In a
study involving 47 surgical ICU patients, the group treated with systemic fluconazole
with APACHE Score II at the time of candiduria did not develop disseminated
candidiasis.25 If the candiduric patient’s clinical condition is too unstable to permit an
incremental approach to determine its cause, or if clinical evidence for disseminated
candidiasis is compelling, systemic antifungal chemotherapy should be given
immediately with fluconazole.
132
Urinary candidiasis
Persistent candiduria in immunocompromised or non-catheterized patients

warrants ultrasound or CT scan of the kidney to exclude clinically silent hematogenous
renal candidiasis or upper tract obstruction and stasis. 28,42
4. If antimicrobial therapy is deemed necessary for a patient with candiduria,

what antifungal agents are effective for treatment?
4.1 The first line of treatment is fluconazole 400 mg loading dose, and then
200 mg/day for 7–14 days. The route of administration depends on patient
status and oral tolerability.
4.2 In certain clinical situations such as prior azole use, refractory

infection or suspicion of drug resistance to fluconazole (e.g., patients with
suspected C. glabrata infection), IV amphotericin B deoxycholate (AmBd)
at a dose of 0.3–1.0 mg/kg per day can be given.
4.3 For patients who will undergo urologic procedures and in whom
candiduria was found to be present, fluconazole 200–400 mg (3–6 mg/kg)
daily or AmBd 0.3–0.6 mg/kg daily for several days before and after the
procedure is recommended.
Summary of Evidence
Studies on the optimal drug for symptomatic candiduria are limited by their
sample sizes, indirectness, study design and quality. One local observational study,4
which included a limited number of patients with candiduria, reported that among the
azoles, fluconazole showed the highest cure rate at 8 out of 9 patients, compared to 7
out of 10 on ketoconazole and 5 out of 8 on itraconazole. The same study showed
higher relapse rates with ketoconazole (30%) and itraconazole (38%) compared to
fluconazole (11%). No failures were seen with 10- to 14-day courses of amphotericin B
in six patients. One randomized multicenter placebo-controlled study involving 316
consecutive asymptomatic/minimally symptomatic candiduria patients showed that
short-term fungal-eradication rates were higher compared with placebo in patients who
received fluconazole at a loading dose of 400 mg followed by 200 mg the next 13 days
for a total of 14 days.23
Fluconazole is the drug of choice for Candida cystitis caused by most species
of Candida (exceptions include infections caused by resistant species such as C.
glabrata and C. krusei). The drug’s in vitro activity and pharmacokinetics make it a good
choice for Candida cystitis as it is highly water soluble and is primarily excreted in the
urine. Fluconazole can be given at a dose of 200–400 mg orally daily for two weeks.13,14
Other azoles are not as useful for cystitis because their active compound is minimally
excreted in the urine: itraconazole <1%, voriconazole <5%, posaconazole <1%. 13
Although the antifungal flucytosine may be useful in fluconazole-resistant Candida
infections, it is not available in the Philippines.
133
Urinary candidiasis
In certain clinical situations such as prior azole use, refractory infection or

suspicion of drug resistance to fluconazole (e.g., patients with suspected C. glabrata
infection), IV AmBd at a dose of 0.3–1.0 mg/kg per day can be given.8
Ascending pyelonephritis due to Candida infection is often seen in
hospitalized patients with the following conditions: diabetes and renal insufficiency,
variable papillary necrosis and obstructive uropathy. 43 Systemic antifungal therapy with
fluconazole 200–400 mg (up to 6 mg/kg) daily for two weeks or AmBd 0.5–0.7 mg/kg
daily for one to seven days, together with adequate drainage of the upper urinary tract,
is essential.14 Relief of obstruction and Investigation of possible local complications
through imaging are of utmost importance.43
Patients who will undergo urologic procedures and in whom candiduria was
found to be present should receive short-course prophylactic therapy with an antifungal
agent.12,28 Unfortunately, the optimal regimen for this indication is yet to be
determined.12 In a case series of four patients, a single-dose IV amphotericin B (0.3
mg/kg) has been shown to be efficacious in the treatment of lower urinary tract
candidiasis, with therapeutic concentrations being observed for considerable periods
after administration.44 A study by Leu et al24 showed a success rate of 72% in
eradicating yeast from the urine with a single IV dose of amphotericin B. The Clinical
Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious
Disease Society of America (IDSA) suggests fluconazole 200–400 mg (3–6 mg/kg)
daily or AmBd 0.3–0.6 mg/kg daily for several days before and after the procedure,
based on low-quality evidence.14
Most cases of fungus balls will require surgical debridement. Successful
usage of IV fluconazole or AmBd has been reported in case series. 30,45 Based on low
quality-evidence, the IDSA guidelines suggest fluconazole 200–400 mg (3–6 mg/kg)
daily, or as an alternative, AmBd 0.5–0.7 mg/kg (with or without flucytosine), to be given
until there is resolution of symptoms or until urine fungal cultures are negative. If there
is access to the renal collecting system, such as the presence of a nephrostomy tube,
AmBd irrigation at a concentration of 50 mg for every liter of sterile water can be given
as adjunctive therapy.14
In renal candidiasis where there is hematogenous renal involvement, high-
dose systemic amphotericin B (>0.6 mg/kg per day) or parenteral fluconazole (6 mg/kg
per day) is recommended in accordance with guidelines for candidemia from the
Mycoses Study Group42 or the more recent IDSA guidelines.14 Duration of treatment is
4–6 weeks.
Echinocandins are extensively metabolized, and very little drug can be
recovered in the urine. However, in a retrospective review of data from the caspofungin
database, this agent was found to be efficacious in three patients who had Candida
pyelonephritis of ascending origin and in whom other antifungal therapies had failed. 46
4. What is the value of bladder irrigation in the management of urinary

candidiasis?
Bladder irrigation with amphotericin B can be used as an adjunct therapy

to systemic antifungal agents in the treatment of refractory cystitis (e.g.,
infections from Candida with either acquired or inherent resistance to
azoles). When used, a continuous irrigation of amphotericin B at a
134
Urinary candidiasis
concentration of 50 mg per liter of sterile water for a period of five days is

recommended.
Summary of Evidence
The use of bladder irrigation with antifungal agents, most commonly amphotericin B, is
not unusual in clinical practice, particularly in other countries. It has been used for the
past several decades despite the absence of high-quality studies to support it.47,48 Three
randomized controlled trials comparing the rate of clearance of candiduria with
fluconazole versus amphotericin B bladder irrigation have been analyzed in one meta-
analysis.24,48-50 All three studies were randomized, but the randomization processes and
allocation generation and concealment processes were not clearly described. All point
estimates of the OR (clearance of candiduria) for the three studies showed trends
towards the use of amphotericin B bladder irrigation at day 1 post-treatment (pooled
OR 0.57 95% CI 0.32–1.0). However, at day 5 post-treatment, both therapies already
showed similar responses (pooled OR 1.51 95% CI 0.81–2.80).50 In two of the three
studies, the use of systemic fluconazole demonstrated prolonged beneficial effects that
were not observed initially.24,48 In fact, in the study by Jacobs et al, at one month after
study enrollment, the all-cause mortality rate was greater among patients treated with
amphotericin B bladder irrigation alone than among those who received oral fluconazole
(41% vs. 22%, respectively; p<0.05).48 The IDSA guidelines have, in fact, discouraged
the use of this strategy due to a high relapse rate. 14 Thus, bladder irrigation with
amphotericin B can be used only as an adjunct therapy to systemic antifungal agents
in the treatment of refractory cystitis (e.g., infections from Candida with either acquired
or inherent resistance to azoles). When used, a continuous irrigation of amphotericin B
at a concentration of 50 mg per liter of sterile water for a period of five days is
recommended over intermittent irrigation.50
135
Urinary candidiasis
Table 21. Summary of Treatment for Urinary Candidiasis

Patient Subset First Line Remarks
Candiduria with It is best to follow
confirmed or suspected treatment guidelines for
disseminated candidemia.‡
candidiasis/candidemia Fluconazole 400–800mg
Clinically unstable (6 mg/kg) IV daily or
patient with candiduria amphotericin B (>0.6
mg/kg per day)§
For patients undergoing Fluconazole 200–400 mg Several studies report
urologic procedures (3–6 mg/kg) daily or AmBd equivalent results with
0.3–0.6 mg/kg daily for the use of bladder
several days before and irrigation with
after the procedure amphotericin B.
However, its cost,
difficulty in
administration and high
relapse rate limit its
use.
Candida cystitis Fluconazole 400 mg loading For non-albicans
dose, and then 200 mg daily species, consider
to complete two weeks amphotericin§
Alternative: AmBd 0.3–0.6
mg/kg daily for one to seven
days§
Candida pyelonephritis Fluconazole 200–400 mg Consider surgical
daily for two weeks interventions, especially
Alternative: AmBd 0.5–0.7 to relieve obstruction if
mg/kg daily for 1-7 days§ there is any; identify
local complications
through imaging.
Urinary fungus ball Surgical removal, plus: If there is access to the
First line: Fluconazole 200– renal collecting system,
400 mg (3–6 mg/kg) daily to such as the presence of
be given until there is a nephrostomy tube,
resolution of symptoms or AmBd irrigation at a
until urine fungal cultures are concentration of 50 mg
negative per liter of sterile water
Alternative: AmBd 0.5–0.7 can be given as
mg/kg adjunctive therapy.
‡ Treatment for candidemia or disseminated candidiasis is beyond the scope of this
guideline. The reader is referred to other relevant documents such as the Clinical
Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious
Disease Society of America, available for download at the IDSA website,
www.idsociety.org.
§ For patients with prior azole use, refractory infection or when there is suspicion of
drug resistance to fluconazole (e.g., patients with suspected C. glabrata infection)
136
Urinary candidiasis
Figure 3. Algorithm for the management of candiduria
137
Urinary candidiasis
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Philippine Clinical Practice

Guidelines on the Diagnosis and

Task Force on UTI 2013, Philippine Practice Guidelines Group in

Uncomplicated Urinary Tract Infections

Organizations: PSMID, POGS, PSN, PUA, PAFP

Uncomplicated Urinary Tract Infection Cluster

Urinary Tract Infection in Pregnancy and Asymptomatic Bacteriuria in

Research Associates: Richelle G. Duque

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1 i

ii Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

The oc s o the idelines as on dia nosis t eatment and

In formulating optimal approaches to the care of both outpatients

The idelines e e not intended to s pe sede a healthca e p o ide s

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Table 1. Strength of Recommendation and Quality of Evidence1,2

Weak Desirable and undesirable effects closely balanced; or uncertain, new

No recommendation Further research is required before any recommendation can be made

High Consistent evidence from well-performed RCTs or strong evidence

Moderate Evidence from RCTs with important limitations or moderately strong

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

se ies o ace to ace meetin s o the tas o ce ith ep esentati es

e ments o the idelines e e p esented in a io s o a incl din

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Woman with ≥1 *dysuria, frequency, urgency, hematuria,

es See Section on UTI in pregnancy

With clear history of

High probability of AUC (~80%)

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Ampicillin or amoxicillin should NOT be used for empirical

T imethop im s l ametho a ole m I o th ee

it o antoin monoh d ate mac oc stals m I o fi e

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1 7

os om cin in a sin le dose is also a ecommended

i mecillinam m I o th ee to se en da s can e sed

inolones sho ld T e sed as a fi st line d despite thei

Duration of treatment for elderly women

Course of action for patients who do not respond to treatment

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

ost t eatment la o ato tests

Recommendations and Summary of Evidence

Table 2. Conditions that define complicated UTI1–7

Presence of an indwelling urinary catheter or intermittent catheterization

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

n ea lie s stematic e ie ent et al also assessed the

The findin s o iesen et al e e simila to the findin s o ent

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Signs/Symptoms Summary Positive Summary Negative Summary Positive Summary

2. What is the best approach in the management of a patient

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

ince the CT on the fi e mana ement app oaches sho ed no

3. Which antibiotics are effective for acute uncomplicated cystitis?

Comment: Collateral damage is the “ecological adverse effects” of

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Ampicillin or amoxicillin should NOT be used for

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Table 5. Percent Resistance of Urinary E. coli (outpatient urine specimens)

T imethop im s l ametho a ole m I o th ee

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Nitrofurantoin monohydrate/macrocrystals (100 mg

Guidelines on Diagnosis and Management of UTI in Adults 2013 Update Part 1

Fosfomycin (3 g in a single dose) is also a recommended

Pivmecillinam (400 mg BID for three to seven days) can