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NOTES ON URINARY TRACT INFECTIONS

Dr. Saleh Mohammad Shoaib, Assistant Surgeon, Fakirhat UHC, Bagerhat

DMC (K – 67), MD resident (Phase – A, Neurology, NINS), Mob: 01757370094

CONTENTS

1. INTRODUCTION TO UTI 9.2. PYELONEPHRITIS IN PREGNANCY

2. ACUTE CYSTITIS OR LOWER UTI 9.3. RECURRENT UTIS IN PREGNANCY

3. COMPLICATED LOWER UTI 10. RENAL ADJUSTMENT OF UTI DRUGS

4. ACUTE PYELONEPHRITIS OR UPPER UTI 10.1. AMINOGLYCOSIDES IN RENAL IMPAIRMENT

5. ASYMPTOMATIC BACTERIURIA 10.2. A REAL LIFE STORY

6. RECURRENT UTI 11. DRUGS FOR OVERACTIVE BLADDER/DETRUSOR


HYPERREFLEXIA
7. RELAPSE UTI
12. INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME
8. CATHER – RELATED UTI
13. EXAMPLES OF PRESCRIBING IN UTI
9. UTI IN PREGNANCY
ST
14. 1 LINE DRUG TREATMENT FOR DIFFERENT UTIs
9.1. ASYMPTOMATIC BACTERIURIA OR CYSTITIS IN PREGNANCY

1. INTRODUCTION TO UTI

DEFINITIONS

Asymptomatic bacteriuria: Isolation of a significant bacterial count in


an asymptomatic patient.

Uncomplicated UTI: Symptomatic bladder infection (cystitis) in a


female with a normal urinary tract.

Complicated UTI: Symptomatic infection of any part of the urinary


tract in a female with a functional or structural urinary abnormality.

Re – infection: Recurrent UTI with the same or different organism,


following clearance of the original UTI.

Relapse: Recurrent UTI with the same organism that has not been
adequately cleared.

EPIDEMIOLOGY

• UTI (acute and recurrent): more common in women (usually cystitis


HOST FACTORS PREDISPOSING TO UTI
occurring in a normal urinary tract). In men and children, UTI is rare
and almost always associated with urinary tract abnormalities (so do
• Female sex***
imaging!).
• Sexual intercourse***
PATHOGENESIS
• Urinary catheter***
• In female, UTI usually caused by ascending colonic flora, i.e. after
perivaginal, perineal, and transurethral colonization, often triggered • Spermicides
by intercourse.
• Urinary stasis/incomplete bladder emptying
• Lactobacillus, a vaginal commensal, prevents uropathogens from
colonizing the perineum — changes in the vaginal pH (menopause/old • Comorbidities (esp. Diabetes mellitus)
age), use of spermicides, or antibiotic treatment may lead to failure of
this defense mechanism. • Institutionalized patient
• Increasing age (reduced estrogen + change in vaginal pH) • Known abnormal urinary tract, stones, indwelling catheter or
ureteric stent.
• Eradication of vaginal commensals
2. ACUTE CYSTITIS OR LOWER UTI
• Urinary tract stone
BACTERIOLOGY
• Highly concentrated urine or failed urinary acidification
E. coli (70 – 90%), S. saprophyticus (5 – 20%), Klebsiella (1 – 2%),
INVESTIGATIONS
Enterococci (1 – 2%), Proteus mirabilis (1 – 2%), Citrobacter,
Enterobacter, Pseudomonas aeruginosa, Staphylococcus aureus,
• Urine dipstick: positive leucocyte esterase + nitrite reductase.
Group B streptococci (all <1% each).
Positive predictive value of 66% and a negative predictive value of
90%. May be modest haematuria or proteinuria.
CLINICAL FEATURES
4
• Clean–catch mid – stream urine (MSU) microscopy: pus cells (>10
• Abrupt onset of frequency*** of micturition and urgency***,
WCC/mL urine) + organisms. WCC casts strongly suggest
nocturia***
pyelonephritis.
• Burning pain in the urethra during micturition*** (dysuria)

• Urine culture: within 2h of collection. If not possible, store at 4 (for
• Suprapubic pain*** (+ tenderness***) during and after voiding
<48h).

• Bacteriuria without pyuria almost always represents contamination. • Intense desire to pass more urine after micturition***, due to
spasm of the inflamed bladder wall (strangury)
• Suspected pyelonephritis:  WCC,  CRP, S. Creatinine, S. Urea, S.
• Cloudy** urine, having an unpleasant odour**
Electrolytes.
• Non – visible or visible haematuria*
• Pregnancy test* if appropriate.
• Patient usually afebrile***
• Imaging: in complicated cases, e.g. fever persists >48h despite
therapy, clinical deterioration, poorly controlled diabetes,
In the elderly, UTI may present as confusion** + incontinence*** (+
immunocompromised, systemic sepsis, recurrent episodes, stone
sepsis!)
former.
ASK ABOUT
 CT – KUB with contrast: investigation of choice (superseded IVU).
• All symptoms described above***
 USG KUB: doesn’t involve radiation or contrast, will exclude
obstruction with hydronephrosis. A negative USG doesn’t exclude • Marital status*** (esp. newly married)
pyelonephritis, and ureteric abnormalities will be missed. Pre– and
post–micturition imaging of the bladder (USG with post – voidal • sexual activity and its relation to symptoms***
residue/PVR) should be performed.
• Previous episodes of UTI***
• Urodynamic flow studies: In male, assess prostate size and bladder
emptying if needed. • Pregnant or not**? amenorrhoea? Having been trying to conceive?

• Cystoscopy: in select cases. • Menstruating or post – menopausal?

WHO NEEDS CLOSER ATTENTION? • Pre–existing bladder irritative (urgency, frequency, stranguary) or
obstructive (poor flow, dribbling, feeling of incomplete evacuation,
• Symptoms > 14 days bladder fullness, incontinence) symptoms**

• Recurrent UTI • H/o urinary tract instrumentation**, stone**, surgery

• Male sex • Any known anatomic/functional abnormality*

• Children • Any anxiety/tension**? Increased symptoms with stress**?

• Pregnant women • Any vaginal discharge/pain on intercourse**? (Suspect vaginitis, UTI


less likely).
• Diabetic patients
• Recent antibiotic use, h/o drug allergy
• Immunocompromised
UTI SUSPECTED গ ক ক
• Proteus UTI? – associated stones
• ক ছ ?ক ই ? PREVENTION

• Drink Plenty of fluid.


• ক ? ঘ ঘ ? ক ঘ ?
• Empty the bladder frequently and completely.
• চ খ ?
• Void before and after intercourse.
• ক ক ?
• Post – coital single dose of antibiotic (who tend to develop UTI
• ক ক ক ই ? following coitus).

• Postmenopausal women with recurrent UTI may benefit from a


• ঙ ক ? গ ? ? ছ?
topical estrogen cream.

• ক ছ ?ক ছ গ? • Daily cranberry juice/tablets may reduce risk of cystitis.

• ? ক ক ? UTI গ জ

• গ কখ ও ছ? গ কখ ও ক
• ২ ও খ ক ।
– ক , ক ,
ক ক ছ ? • চ খ ।চ ক ।
গ ক ।
• ছ? ক ছ ?
• ক ক ক ক জ ক ।
• ক ক গ ছ? ক গ?
• ক ।
• কখ ও ক কছ ক ছ ?
• গও ক । জ
• কখ ও ক ক ছ ?
ক জ ক ক ।
কখ ও ক ক ছ ?
TREATMENT
• ক ক ? ক ? ক ক ঘ
• Encourage high fluid intake, e.g. >2L/day.
ঘ ?
• Symptomatic relief: Hot sitz baths or urinary analgesics (Potassium
• ক ? ক citrate syrup).
ক ?
• Anti – microbial therapy: Avoid broad–spectrum agents, e.g: co–
amoxiclav, quinolones and cephalosporins. They increase the risk of
• ক ক ঔষ ক ছ ?
antibiotic resistance (as well as Clostridium difficile). Amoxicillin less
effective at eradicating vaginal and peri–urethral colonization.
• ক ঔষ জ ছ? গ ক ঔষ ক ক
ছ ? PROGNOSIS

DIFFERENTIAL DIAGNOSIS Typically respond rapidly to therapy. Failure to respond suggests


antibiotic resistance or anatomic abnormalities (do further
Women: Vulvovaginitis, PID. Men: urethritis (presence of urethral investigations!).
discharge), prostatitis (presence of prostatic tenderness).

Noninfectious causes of cystitis–like symptoms include bladder


carcinoma, interstitial cystitis, voiding dysfunction disorders, and
psychosomatic disorders (anxiety disorder***).
EMPIRICAL ORAL THERAPY FOR ACUTE CYSTITIS
Duration
Name Dose Cost Comment
Female Male
First line
Trimethoprim– 1 DS tablet 3 days 7 – 14 days 480 mg tab = • Increasing resistance noted.
Sulfamethoxaz BD 1.5 tk • A/E: megaloblastic anemia, leukopenia, granulocytopenia,
ole (Cotrim + 960 mg (DS) tab nausea, vomiting, fever, vasculitis, skin rashes, exfoliative
DS) = 2 tk dermatitis, photosensitivity, urticaria, diarrhea, Stevens–Johnson
syndrome (uncommon, <1% of treatment courses), stomatitis,
conjunctivitis, arthritis, hepatitis, polyarteritis nodosa, psychosis.
Nitrofurantoin 100 mg SR 5–7 7 – 14 days 50 mg tab = 4 tk • Resistance emerges slowly.
(Nintoin + SR) BD or 50 – days 100 mg tab = 6 • Contraindicated in significant renal insufficiency.
100 mg 6 tk • Should not be used to treat upper UTI.
hrly 100 mg SR cap = • A/E: Anorexia, nausea, vomiting.
20 tk • Avoid at term pregnancy.
Fosfomycin 3 g sachet single 3-g dose 3 g sachet = 350 • Males with Prostatitis: 3–g dose every 3 days for 21 days
(Fosamin) dose every 3 days tk • Do not use to treat pyelonephritis.
for 9 days • Pregnancy safe.
nd
2 line
Ciprofloxacin 250 mg BD 3 days 7 – 14 days 250 mg tab = 8.5 tk • Avoid fluoroquinolone use for uncomplicated UTI.
(Cipro – A, 500 mg tab = 14 tk • Drug of choice for complicated UTI.
Ciprocin) 750 mg tab = 18 tk • Avoid during pregnancy.
Levofloxacin 250 – 500 3 days 7 – 14 days 250 mg tab = 8 tk • A/E: Nausea, vomiting, diarrhea, damage of growing
st
(Levoxin) mg daily 500 mg tab = 15 tk cartilage > arthropathy (so, not 1 line for < 18 y), tendinitis
750 mg tab = 20 tk (in adults, risk of tendon rupture! Risk factors for tendinitis:
advanced age, CKD, concurrent steroid use).
Alternatives (Try to avoid in uncomplicated cystitis)
Cephalexin 500 mg 3-7 7 – 14 days 250 mg cap = 7 tk • Pregnancy safe
(Cefalex) every 6 – days 500 mg cap = 8.5 tk
12 hours
Co – Amoxiclav 500/125 3 days 7 – 14 days 375 mg tab = 16 tk • Pregnancy safe
(Demoxiclave, mg BD 625 mg tab = 24 tk • Well tolerated
Moxaclav) • A/E: Hypersensitivity
Cefpodoxime 100 mg BD 3 days 7 – 14 days 100 mg tab = 17 tk • Pregnancy safe
(Ximeprox) 200 mg tab = 28 tk
BD = every 12 hours

N.B: Don’t prescribe Moxifloxacin for UTI, it does not achieve adequate urinary levels.

Fig: Empirical therapy for acute cystitis in women


3. COMPLICATED LOWER UTI Urinalysis: pyuria, bacteriuria, varying degrees of hematuria. White
cell casts may be seen.
• At–risk patients: Male sex, recent urinary tract instrumentation,
recent antibiotics, diabetes mellitus, immunosuppressed, Urine culture: heavy growth of the offending organism
obstruction, structural abnormalities, functional abnormality (e.g.
Blood culture: may be positive
neurogenic bladder, reflux), foreign body, renal failure.
IMAGING
• Empirical therapy should be started immediately (e.g.
fluoroquinolones for 7 – 10 days), but antibiotic therapy should
Renal USG: may show hydronephrosis from a stone or other source
always be tailored against urine culture and sensitivity results.
of obstruction.

• In the immunocompromised, consider additional single–dose


CT – KUB (with contrast): may demonstrate decreased perfusion of
aminoglycoside (e.g. gentamicin 3 – 5mg/kg IV or IM) [Caution!
the kidney or focal areas within the kidney and nonspecific
Exclude pre – existing renal impairment]
perinephric fat stranding.

4. ACUTE PYELONEPHRITIS OR UPPER UTI DIFFERENTIAL DIAGNOSIS

• Infectious inflammatory disease involving the kidney parenchyma • Acute intra – abdominal disease such as appendicitis,
and renal pelvis. cholecystitis, pancreatitis or diverticulitis – must be excluded.

Causative agents: • A normal urinalysis is usually seen in GIT disorders; however,


inflammation from adjacent bowel (appendicitis or diverticulitis) may
• Most common: Gram – negative bacteria e.g: E coli, Proteus, result in hematuria or sterile pyuria.
Klebsiella, Enterobacter, Pseudomonas
• Abnormal liver biochemical tests or elevated amylase levels may
• Less common: Gram – positive bacteria e.g: Enterococcus faecalis, assist in the differentiation.
Staphylococcus aureus.
• Lower lobe pneumonia is distinguishable by the abnormal Chest X
PATHOGENESIS – ray.

Infection usually ascends from the lower urinary tract— with the • Exclude acute cystitis.
exception of S. aureus, which usually is spread by a hematogenous
route. • In males, the main differential diagnosis for acute pyelonephritis
also includes acute epididymitis (painful enlargement of
SYMPTOMS epididymis) and acute prostatitis (prostate tenderness).

• Fever TREATMENT

• Flank pain • Fluoroquinolones (e.g. Ciprofloxacin 250 – 500 mg BD PO) or


Levofloxacin 250 mg OD for 14 days.
• Shaking chills, rigors
rd
• Alternatives include Co – Amoxiclav IV, then PO, or a 3
• Night sweats
generation cephalosporin IV, then PO for 14 days.
• Irritative voiding symptoms (urgency, frequency, dysuria)
• Consider additional single–dose gentamicin 3 – 5mg/kg IV.
• Associated nausea, vomiting and diarrhea are common
• Rehydration with 0.9% NaCl.
SIGNS
• Appropriate analgesia and anti – emetics.
• Costovertebral/renal angle tenderness – usually pronounced

• Fever

• Tachycardia

May be systemically unwell, with progression to sepsis and shock a


possibility. In immunocompromised (and children), all of the listed
symptoms/signs may be absent — so maintain a high index of
suspicion, esp. if unexplained fever.

LAB FINDINGS

CBC: WBC, left shift.


• In women, recurrent infections are common and investigation is
justified only if infections are frequent (> 3 per year) or unusually
severe.

• Identify underlying risk factors and causes and treat any


remediable cause accordingly***.

Fig: Treatment of acute pyelonephritis • If an underlying cause cannot be identified and/or treated, give
suppressive antibiotic therapy to prevent recurrence and reduce
TREATMENT RESPONSE
risk of sepsis and renal damage.
• Fevers may persist for up to 72 hours even with appropriate
antibiotics.

• Failure to respond within 48 hours warrants imaging (CT or USG) to


exclude complicating factors that may require intervention.

• Catheter drainage may be necessary in the face of urinary


retention and nephrostomy drainage if there is ureteral obstruction.

• In inpatients, IV antibiotics are continued for 24 hours after the


fever resolves, and oral antibiotics are then given to complete a 14–
day course of therapy.

PROGNOSIS

• With prompt diagnosis and appropriate treatment, acute


pyelonephritis carries a good prognosis.

• Complicating factors, underlying kidney disease, and increasing


patient age may lead to a less favorable outcome.

COMPLICATIONS • Urine should be cultured at regular intervals.

• Sepsis + shock. • Regimen: 2 or 3 antibiotics in sequence, rotating every 6 months


(to prevent emergence of resistance).
• Emphysematous pyelonephritis in diabetic patients.
PROPHYLAXIS
• Scarring or chronic pyelonephritis (if coexistent kidney disease
present) • Efficacy: Can reduce recurrence rates by 95%.

• Abscess formation (if inadequate therapy) • Indication: If no remediable underlying cause is identified, for
cystitis > 3 episodes per year.
5. ASYMPTOMATIC BACTERIURIA
• Pre – requisites: Ensure any current infection is successfully
5
• Definition (♀): isolation of the same organism (≥ 10 cfu/mL) in eradicated first. Exclude any anatomic abnormality (e.g: stones,
two consecutive urine samples. reflux, fistula etc.) by imaging (including bladder emptying),
cystoscopy etc.
• Common.
• Caution: Risk of developing resistance.
• Patient has no symptoms attributable to the urinary tract.
• Duration: Initially, 6 to 12 months.
• Associated with: sexual activity, diabetes, institutionalization,
impaired urinary voiding, indwelling device (e.g. catheter or stent). • Regimen:

• Treatment is required in infants, pregnant women and those with If UTI related to sexual activity (give each dose after intercourse):
urinary tract abnormalities.
Trimethoprim 200 mg or
6. RECURRENT UTI
Co – trimoxazole 480 mg or
• Definition: > 4 culture–proven UTIs in a year. Re - infection with
the same or different organism, following clearance of the original Nitrofurantoin 50 mg
UTI.
 For others, give nightly dose in a monthly rotation as:

Trimethoprim 100 mg for 1 month


then Nitrofurantoin 50 mg for 1 month • ক ক গছ

then Cefalexin 250 mg for 1 month. ক estrogen cream ক ।

Alternatives include Co – trimoxazole 480 mg or Amoxicillin 250 mg. 7. RELAPSE OF UTI

• These may be adapted, according to previous culture results. DEFINITION

Return of symptoms following an initial UTI with a culture of the


same organism that has not been adequately cleared.

PATHOGENESIS
Fig: Prophylactic therapy against recurrent UTI
Offending organism not adequately cleared due to –
• Counsel about the potential development of oral/vaginal
candidiasis and its treatment. • Inappropriate therapy with resistant drug

• Postmenopausal women with recurrent cystitis: Treat with • Inadequate duration of therapy
vaginal estrogen cream 0.5 g nightly for 2 weeks, then twice weekly
thereafter. • Urinary tract abnormality impending adequate clearance e.g:
prostatic enlargement, stone, atonic bladder etc.
ADVICE TO PREVENT RECURRENT UTI***
TREATMENT
• Fluid intake of at least 2 L/day
Prolonged (2 – 4 weeks) course of antibiotics effective against
• Regular complete emptying of bladder offending pathogen.

• Double voiding may help bladder emptying


8. CATHETER – RELATED UTI
• Good personal hygiene
• Bacteriuria occurs in 3 – 10% of patients with an indwelling
• Establish whether related to intercourse catheter/per day catheterized.

• Emptying of bladder before and after sexual intercourse • No role for screening asymptomatic patients.

• Cranberry juice/tablets may be effective DIAGNOSIS

5
• Spermicides or spermicide – coated condoms should be  Cultures positive for >10 cfu/mL and
discouraged
 Heavy pyuria (although pyuria is not always a reliable marker of
• Vaginal estrogen creams in post – menopausal women infection in this context).

N.B: Factors NOT predisposing to UTI: voiding after intercourse, TREATMENT


showering, hot baths/saunas, tights/synthetic fabrics.
 Only required if significant local symptoms/systemic upset.

RECURRENT UTI গ জ  If required, continue antimicrobials for at least 7 days.

• ২ ও খ ক ।  Remove the catheter as soon as possible, as a surface biofilm acts


as a reservoir of infection.
• চ খ ।চ ক ।
PREVENTION IS BEST***
গ ক ।
• Use catheters only when necessary
• ক ক ক ক জ ক ।
• Remove catheters when no longer needed
• ক ।
• Use antimicrobial catheters in high – risk patients

• গও ক । জ • Use external collection devices (e.g: condom catheter) in select


ক জ ক ক । men

• Cranberry juice ক (Cran – B). • Identifying significant post - void residuals by USG

• Maintaining proper insertion techniques


•ক ক ক ।
• Utilizing alternatives such as intermittent catheterization
9. UTI IN PREGNANCY DRUGS CONTRAINDICATED/TO BE AVOIDED

rd
RISK FACTORS  Sulfonamides: Avoid in the 3 trimester > may interfere with
bilirubin binding > risk of neonatal jaundice and kernicterus.
• The urinary tract is especially vulnerable to infections during
pregnancy because:  Fluoroquinolones: potential teratogenic effects on fetal cartilage
and bone.
 Altered secretions of steroid sex hormones

 Pressure exerted by the gravid uterus on the ureters and bladder


> hypotonia and congestion > urinary stasis.

 Labor, delivery and urinary retention postpartum also may initiate


or aggravate infection.

BACTERIOLOGY Fig: Treatment of cystitis in pregnancy

• E. coli (80 – 90%), Proteus, Klebsiella, or Gram +ve organisms may FOLLOW UP
also be implicated.
• Repeat Urine microscopy and culture & sensitivity monthly to
• Group B Streptococcus (GBS) infection near delivery may lead to confirm eradication.
vaginal colonization and serious neonatal sepsis, so penicillin
prophylaxis should be given during labour. 9.2. PYELONEPHRITIS IN PREGNANCY
SCREENING • Hospitalize.

Evaluation for asymptomatic bacteriuria at the first prenatal visit is • Rehydration with 0.9% NaCl as required.
recommended for all pregnant women. (Urine microscopy, culture)
• Ceftriaxone 1g IV daily or Cefotaxime 1 – 2 g IV 6 hourly.
UTI DRUGS IN PREGNANCY
• Alternative: Ampicillin 1g IV 6 hourly + Gentamicin 1.5mg/kg 8
Safe in pregnancy Unsafe in pregnancy hourly.
st
• Penicillins • Sulfonamides (1 trimester:
rd
• Cephalosporins teratogenic. 3 trimester: • Continue IV antibiotics for 24 - 48 hours after the fever resolves,
• Nitrofurantoin (Avoid at term.  may interfere with bilirubin
and oral antibiotics are then given to complete a 14–day course of
risk of neonatal jaundice if used binding > risk of neonatal
within 30 days of delivery). jaundice and kernicterus) therapy.
• Fosfomycin • Fluoroquinolones (potential
• Trimethoprim (safe after 1st teratogenic effects on fetal • If the patient is immunocompromised and/or has incomplete
trimester). cartilage and bone) urinary drainage, then seek urgent microbiological advice.

N.B: Fluoroquinolones (e.g: ciprofloxacin): should be avoided,


9.1. ASYMPTOMATIC BACTERIURIA OR CYSTITIS IN unless resistant organisms are cultured.

PREGNANCY Co – trimoxazole: needs to be used with caution (sulfonamides


should not be used in the 3rd trimester).
FIRST LINE ORAL OPTIONS (PRIOR TO CULTURE)

 Nitrofurantoin*: 100 mg SR twice daily (or 50 mg 6 hourly) for 7


9.3. RECURRENT UTIS IN PREGNANCY
days or
PROPHYLAXIS
 Cefalexin*: 500 mg twice daily (or 250 mg 6 hourly) for 7 days
• Indication: > 1 episode of UTI in normal urinary tract or 1 episode
with an abnormal urinary tract during pregnancy
OTHER DRUG CHOICES

• Duration: For the remainder of the pregnancy


 Amoxicillin: 250 mg 6 hourly for 7 days (often first choice if
sensitivities known)
• Safe and effective regimen: Post – coital Cefalexin 500 mg PO stat
and/or Cefalexin 500 mg every night for 1 month, alternating with
 Ampicillin: 500 mg 6 hourly for 7 – 10 days for group B
Nitrofurantoin 100 mg every night.
Streptococcus infections — and inform the patient's antenatal
service, as prophylactic antibiotics may be indicated during labour
and delivery.
10. RENAL ADJUSTMENT OF UTI DRUGS

250 – 500 mg 250 – 500 mg 250 – 500 mg


stat then 125 stat then 125 stat then
Oral: 250 – 500 mg 12 – 24 mg 12 – 48 125 mg 12 – 48
500 mg stat
mg 12 – 24 hourly. hourly. hourly. hourly. Dose as in GFR Dose as in GFR <
Levofloxacin IV: 250 – 750 mg < 10 mL/min. 10 mL/min.
then 250
Alternative: 500
Alternative: 500 – 750 mg stat mg daily.
12 – 24 hourly mg stat then
then 250 – 750 mg every 24 – 48
250 – 500 mg
hours.
every 48 hours.
250 mg 6 hourly 250 – 500 mg 250 – 500 mg Dose as in
Dose as in GFR Dose as in GFR <
Cefalexin or 500 mg every No change every 8 – 12 every 8 – 12
< 10 mL/min. 10 mL/min.
GFR = 10 –
8 – 12 hours hours hours 20 mL/min.
Dose as in
Dose as in GFR Dose as in GFR <
Fosfomycin 3 g sachet stat No change No change Contraindicated
< 10 mL/min. 10 mL/min.
GFR = 10 –
20 mL/min.
10 – 30: 100 – Dose as in
100 – 200 mg 12 30 -50: No 100 – 200 mg Dose as in GFR Dose as in GFR <
Cefpodoxime hourly change
200 mg 24
24 hourly < 10 mL/min. 10 mL/min.
GFR = 10 –
hourly 30 mL/min.
No change Dose as in GFR Dose as in GFR < 2 g every 12
Ceftriaxone IV: 1 – 4 g daily No change No change
(max. 2 g/d) < 10 mL/min. 10 mL/min. – 24 hours.
Oral: 250 mg – 1 g
6 hourly Dose as in
250 mg – 2 g 6 250 mg – 2 g 6 Dose as in GFR Dose as in GFR <
Ampicillin IM/IV: 500 mg – 2 No change
hourly hourly < 10 mL/min. 10 mL/min.
GFR = 10 –
g every 4 – 6 20 mL/min.
hours
HD = hemodialysis, CAPD = continuous ambulatory peritoneal dialysis, CVVH: continuous venovenous haemofiltration

10.1. AMINOGLYCOSIDES IN RENAL IMPAIRMENT which didn’t heal. O/E there was tenderness over Lt. ankle joint
proper but no significant swelling or fever. Pt. was diabetic but it
• They must always be used with caution in renal impairment, as was well controlled according to last reports few days back. S.
they undergo renal clearance, have a narrow therapeutic window, creatinine was 1.0. My provisional diagnosis was Septic arthritis of
and are nephrotoxic. Lt. ankle with cellulitis over Lt. leg and foot. D/D was only cellulitis,
not septic arthritis (as there was no significant swelling over Lt.
• A vicious cycle of rising drug levels and worsening renal function ankle or fever). So, I requested them to be admitted here and get
often results! treatment.

• They are freely filtered by the glomerulus (so, dose is adjusted I started IV Flucloxacillin 2g 6 hrly, IV Gentamicin 80 mg 3 vial once
according to GFR) and then partially taken up by tubular cells. This daily (wt. = appx. 50 kg), IV Ceftriaxone 2g 12 hrly, IV
can cause tubular cell injury > Acute tubular necrosis (ATN). Metronidazole 500 mg 8 hrly. For pain I gave IM Diclofenac 75 mg
12 hrly, IM Tramadol 100 mg 8 hrly. Fluids, anti – ulcerants, anti -
• Factors increasing risk of both nephrotoxicity and ototoxicity:
emetics were also given.
prolonged treatment, dehydration, concomitant diuretic use,
obstructive jaundice, hypokalaemia, and hypomagnesaemia. I was at a loss whether to aspirate Lt. ankle joint or not. Because if
it was only cellulitis and not septic arthritis, an attempt to aspirate
• Adjust dose to achieve peak plasma levels that are bactericidal
will introduce pathogen into joint and result in iatrogenic septic
whilst permitting low trough levels that avoid toxicity.
arthritis! Later on after initiating treatment, I gathered the courage
to aspirate the joint and yes! scanty but purulent-looking whitish
• Always, always and always consult an expert medicine
material came out!
specialist/nephrologist before prescribing aminoglycosides in renal
impairment or for prolonged duration***.
Treatment continued for 2 - 3 days. Pain subsided and pt. was
feeling better. Then something happened.
• Measure renal function (e.g: S. creatinine and electrolytes)
repeatedly or on daily basis while continuing aminoglycoside***. th
On 4 day, at Fazr, pt. party met me as masjid and told that
something was wrong. I went to see the pt. after Fazr. She was
10.2. A REAL LIFE STORY
drowsy, disoriented. No focal neurological signs. BP was around
120/70. Pt. was catherised and urine output was low. I thought it
Few months ago, mother of one of my close acquaintances here in
was because the pt. was not taking adequate fluids due to sickness
Fakirhat was presented with the complaints of severe pain over Lt.
and the drowsiness was due to tramadol accumulation. I didn’t
ankle. Firstly, it started as an ulcer over lateral aspect of Lt. ankle
have my Littman cardiac IV with me and govt. supply stethos
weren’t much good, so I didn’t check lung bases. Instant CBG was 12. INTERSTITIAL CYSTITIS/PAINFUL BLADDER
normal. I ordered 1 L Normal saline in an attempt to dilute
SYNDROME
intravascular tramadol and improve urine output.
• Diagnosis of exclusion.
Coming back to my room, I studied tramadol accumulation from
different books and prayed to Allah jalla jalaluhu for a good • Affects both sexes (F > M). Mean age of onset = 40 y.
outcome. During morning follow up, pt. didn’t improve. Now BP
was around 180/100. Lung bases had definite creps! Urine output • Likely to report bladder problems in childhood (F > M).
was scanty (appx. 30 ml in last 24 hours).
• Etiology unknown.
Then it all came clear as a cloudless sky at an autumn afternoon.
• Most likely not a single disease rather several diseases with similar
With help from my colleague (ex - FCPS part 2 trainee in Medicine), symptoms.
oliguria, acutely high BP, features of pulmonary edema and
drowsiness meant one and only one thing – AKI! (Another • About half of patients may have spontaneous remission with avg.
possibility was Sepsis with organ failure – suggested by my 8 months without treatment.
Abbajan over phone so it was a good differential)
• Associated diseases: Severe allergies, irritable bowel syndrome or
There were 2 probable culprits. Number 1, Gentamicin. Number 2, inflammatory bowel disease.
Diclofenac.
• Ask about exposure to pelvic radiation or cyclophosphamide
Then we referred her to Khulna medical college hospital (As therapy.
electrolytes aren’t available here and creatinine wasn’t up to the
• Patients must have a negative urine culture and cytology and no
mark and we didn’t want to waste any more time).
other obvious cause such as radiation cystitis, chemical cystitis
Pt. party kept contact with me and updated me time to time. She (cyclophosphamide), vaginitis, urethral diverticulum, or genital
was admitted and treatment was started. She didn’t regain herpes.
consciousness. After some days doctors said that she had
SYMPTOMS
developed stroke.
• Pain, pressure or discomfort with bladder filling that is relieved
And days later, the news came as a sneaking cold viper.
with urination.
The pt. passed away from this life to the life hereafter, after living
• Urgency, frequency, nocturia: commonest symptoms with a
life of a religious, pious woman, leaving behind husband, son,
dramatic exaggeration of normal sensations.
daughter – in – law and others thunderstruck, crying.
Signs
I was invited to the janaja (which was to be performed during my
office time), so I gently refused, as I was busy serving just another
• Examination should exclude genital herpes, vaginitis or a urethral
woman, or man, having some pain, or Diabetes, or high blood
diverticulum.
pressure, or something else.
LAB FINDINGS
So, my dear readers, be cautious when prescribing
aminoglycosides – do renal function before and during therapy Urinalysis, urine C/S, urine for malignant cell: normal.
repeatedly, I repeat, repeatedly.]
Urodynamic study: can be done to assess bladder sensation and
11. DRUGS FOR OVERACTIVE BLADDER/DETRUSOR compliance and to exclude detrusor instability.
HYPERREFLEXIA
CYSTOSCOPY
Firstly, exclude and treat any treatable cause (e.g: UTI, BPH), restrict
Hydrodistention: Distend the bladder with fluid to detect
evening fluid and voluntarily void frequently. If these fail, try
submucosal hemorrhage (glomerulations) or ulcers (may or may
following drugs.
not be present). Measure bladder capacity [pt. with very small
Dose bladder capacities (< 200 mL): unlikely to respond to medical
Name Cost Comment therapy].
(mg/d)
Propantheline (Tab. 10 – 15 15 mg/8 tk • Anti –
Prokind) cholinergic Biopsy: to exclude carcinoma, eosinophilic cystitis, TB cystitis etc.
Tolterodine (Tab. 2–4 2 mg/3 tk effects.
Ucol 2) • Predisposes DIFFERENTIAL DIAGNOSIS
Solifenacin (Tab. 5 – 10 5 mg/15 tk to UTI and
Solider, Utrobin) 10 mg/30 tk acute urinary Radiation cystitis/cyclophosphamide cystitis: take history.
Mirabegron (Tab. 25 – 50 25 mg/30 tk retention.
Mirabeg, M - beg) 50 mg ER/55 tk Bacterial cystitis, genital herpes and vaginitis: exclude by urinalysis,
culture, and physical examination.
Urethral diverticulum: indurated mass on urethral palpation that Symptomatic relief: hydrodistention (appx. 20–30% patients
st
causes expression of pus from urethral meatus. improve), Amitriptyline 10 - 75 mg/d (1 line), Nifedipine 30 - 60
mg/d, transcutaneous electric nerve stimulation (TENS),
Urethral carcinoma: firm mass on palpation. acupuncture, stress reduction, exercise, biofeedback, massage,
pelvic floor relaxation.
TREATMENT
Surgical therapy: only a last resort and may require cysto -
No cure.
urethrectomy with urinary diversion.

13. EXAMPLES OF PRESCRIBING IN UTI

Example 1 – Acute uncomplicated cystitis in non – pregnant Fosamin 3 g – 1 packet with ½ glass water – one dose every 3 days
menstruating female: A 28 y old sexually active female presented for 9 days or
with abrupt onset of urgency, frequency of micturition and dysuria.
Urine is foul smelling. She had one such episode in her teens, which Cap. Nintoin SR 100 1 + 0 + 1 for 7 - 14 days.
was succesfully treated with some oral medications. O/E there is
Example 4 – Recurrent UTI in non – pregnant female: A 39 y old non
suprapubic tenderness but renal angle tenderness is absent.
– pregnant female presented with culture proven cystitis. She had 3
Pregnancy test negative.
more similar episodes in the current year, culture was positive for
Management different organisms each time.

Ask necessary questions and give advice*** Management

Diet: Plenty of fluid (>2 L/day). Ask necessary questions and give advice***

Drugs: Cap. Nintoin SR 100 1 + 0 + 1 for 7 days or Identify underlying risk factors and causes and treat any remediable
cause***
Fosamin 3 g – 1 packet with ½ glass water – single dose or
Diet: Plenty of fluid (>2 L/day)
Tab. Cotrim DS 1 + 0 + 1 for 3 days
Firstly, eradicate current infection. Give drug according to culture
Example 2 – Acute uncomplicated cystitis in pregnant female: A 32 sensitivity reports for minimum 7 days.
y old 31 wks pregnant female presented with features of cystitis.
Drugs: Cap. Nintoin SR 100 1 + 0 + 1 for 7 days or
Management
Tab. Cotrim DS 1 + 0 + 1 for 7 days or
Ask necessary questions and give advice***
Fosamin 3 g – 1 packet with ½ glass water – single dose (or multiple
Diet: Plenty of fluid (>2 L/day). doses if needed) or

Drugs: Cap. Nintoin SR 100 1 + 0 + 1 for 7 days or Tab. Ciprocin 500 1 + 0 + 1 for 7 days or

Cap. Cefalex 500 1 + 0 + 1 for 7 days or Tab. Levoxin 250/500 0 + 0 + 1 for 7 days

Cap. Moxacil 250 1 + 1 + 1 + 1 for 7 days or Next, give prophylaxis for 6 to 12 months.

Fosamin 3 g – 1 packet with ½ glass water – single dose (or multiple If UTI is related to sexual activity, give post – coital prophylaxis:
doses if needed)
Drugs: Tab. Cotrim 480 each dose after intercourse or
Example 3 – Acute cystitis in male: A 36 y old male presented with
features of cystitis. Urine microscopy and culture confirms cystitis. Tab. Nintoin 50 mg each dose after intercourse
There is no tenderness on prostate palpation during DRE.
For others, give continuous prophylaxis (nightly dose in a monthly
Management rotation. Use 2/3 antibiotics by rotation every 6 months).

Ask necessary questions and give advice*** Drugs: Tab. Nintoin 50 mg 0 + 0 + 1 for 1 month then

Diet: Plenty of fluid (>2 L/day). Cap. Cefalex 250 mg 0 + 0 + 1 for 1 month then

Drugs: Tab. Ciprocin 500 1 + 0 + 1 for 7 – 14 days or Tab. Nintoin 50 mg 0 + 0 + 1 for 1 month then

Tab. Levoxin 250/500 0 + 0 + 1 for 7 – 14 days or Cap. Cefalex 250 mg 0 + 0 + 1 for 1 month then

Tab. Cotrim DS 1 + 0 + 1 for 7 – 14 days or Tab. Nintoin 50 mg 0 + 0 + 1 for 1 month then


Cap. Cefalex 250 mg 0 + 0 + 1 for 1 month. Example 7 – Acute pyelonephritis: A 39 y old female presents with
high grade fever, shaking chills and rigor, irritative voiding
Tab. Cotrim 480 mg 0 + 0 + 1 for 1 month then symptoms. She has severe renal angle tenderness in Lt. side.

Cap. Moxacil 250 mg 0 + 0 + 1 for 1 month then Management

Tab. Cotrim 480 mg 0 + 0 + 1 for 1 month then Ask necessary questions and give advice***

Cap. Moxacil 250 mg 0 + 0 + 1 for 1 month then Identify underlying risk factors and causes and treat any remediable
cause***
Tab. Cotrim 480 mg 0 + 0 + 1 for 1 month then
Do Urine C/S (and other tests) immediately***
Cap. Moxacil 250 mg 0 + 0 + 1 for 1 month.
Decide whether to hospitalize or not.
[N.B: Do urine C/S regularly. Antibiotics may be adapted, according
to culture results.] Non – hospitalized:

Example 5 – Recurrent UTI in pregnant female: A 35 y old 24 wks Diet: Plenty of fluid (>2 L/day).
pregnant female presented with features of cystitis. Urine R/E shows
pyuria and bacteriuria. She had 1 similar episode 1 month back, Drugs: Tab. Ciprocin 500 1 + 0 + 1 for 14 days or
which was treated with 7 days of oral Nitrofurantoin.
Tab. Levoxin 750 0 + 0 + 1 for 14 days or
Management
Tab. Cotrim DS 1 + 0 + 1 for 14 days.
Ask necessary questions and give advice***
(Give drug according to C/S)
Identify underlying risk factors and causes and treat any remediable
cause*** Hospitalized:

Diet: Plenty of fluid (>2 L/day) Diet: Plenty of fluid (>2 L/day).

Either, give only post – coital prophylaxis. 1. Inf. 0.9% Normal saline as needed to rehydrate

Drugs: Cap. Cefalex 500 mg each dose after intercourse alternating 2. Inj. Anadol 100 mg 1 amp. IM 8 hrly and SOS
with Tab. Nintoin 100 mg each dose after intercourse for the
3. Inj. Emistat 8 mg 1 vial IV 8 hrly and SOS
remainder of the pregnancy
4. Inj. Gentin 80 mg 5 mg/kg single dose IV stat
Or, give continuous antepartum prophylaxis.
5. Inj. Ceftron 1g 1 vial IV stat and BD or Inj. Augment 1.2 g 1 vial IV
Drugs: Cap. Cefalex 500 mg 0 + 0 + 1 for 1 month then
stat and 8 hrly for 24 hrs after fever resolves (max. 14 days)
Tab. Nintoin 50 mg 0 + 0 + 1 for 1 month (thus alternate these 2 followed by one of
drugs every month for the remainder of the pregnancy)
6. Tab. Ciprocin 500 1 + 0 + 1 for rest of 14 days or
Example 6 – Acute complicated cystitis in female: A 26 y old female
Tab. Levoxin 750 0 + 0 + 1 for rest of 14 days.
has h/o trauma to lower back. Since then she has features of atonic
bladder for which she needs intermittent catheterization. Now she
(Give drug according to C/S)
presents with features of cystitis.
Example 8 – Asymptomatic bacteriuria: A 32 y old female came to
Management
you with her urine C/S report showing growth of E. coli. She has no
features of cystitis e.g: frequency of micturition, urgency, dysuria
Ask necessary questions and give advice***
etc. Repeat urine C/S gives same result. Still she has no features
Identify underlying risk factors and causes and treat any remediable attributable to UTI. Pregnancy test negative. She has no known
cause*** urinary tract abnormalities.

Do Urine C/S (and other tests) immediately***. Management

Diet: Plenty of fluid (>2 L/day). No treatment required.

st
• Start empirical therapy (1 line: Fluoroquinolones) immediately. Example 9 – Overactive bladder/detrusor hyperreflexia: A 28 y
Later, give antibiotic according to urine C/S. female presents with the complaints of unilateral loss of vision and
urgency of micturition which she can’t control. 2 years back, she
Drugs: Tab. Ciprocin 500 1 + 0 + 1 for 7 – 10 days or developed ataxia and MRI brain showed demyelinating plaque in
cerebellum. She is investigated thoroughly and ultimately diagnosed
Tab. Levoxin 250/500 0 + 0 + 1 for 7 – 10 days. as a case of Multiple sclerosis. She is now on steroids. There is no
pyuria. Urine C/S reveals no organism. How to control urgency of Hospitalize if required.
micturition?
Diet: CKD diet. Restrict fluid, protein and potassium.
Management
Drugs: Tab. Levoxin 250/500 mg 1 tab stat then 250 mg ½ + 0 + ½ for
Drugs: Tab. Ucol 2 1 + 0 + 1 – cont. or 7 - 10 days or

Tab. Solider 5 1 + 0 + 1 – cont. or Tab. Ciprocin 500 1 + 0 + 1 for 7 – 10 days or

Tab. M – beg 0 + 0 + 1 – cont. or Fosamin 3 g – 1 packet with ½ glass water – single dose or

Tab. Prokind 15 0 + 0 + 1 – cont. Tab. Cotrim DS 1 + 0 + 1 for 7 – 10 days.

Example 10 – Catheter – related UTI: A 63 y old female is (Give drug according to C/S)
catheterized after an event of hemorrhagic stroke. She has no
features of cystitis. There is pyuria and bacteriuria. A decision to Example 13 – Acute pyelonephritis in male with renal impairment:
treat has to be made. A 65 y old male with CKD stage V (eGFR = 8 mL/min) presents with
high grade fever, chills and rigor. O/E there is Rt. renal angle
Management tenderness. Pt. can’t be referred to a higher center with dialysis
facilities due to some reasons.
Do not treat unless significant local symptoms/systemic upset.
Management
Remove the catheter as soon as possible.
Hospitalize immediately.
Example 11 – Relapse UTI: A 29 y old female was diagnosed as a
case of uncomplicated cystitis. She was prescribed Nitrofurantoin 50 Consult the most senior nephrologist/ Medicine specialist urgently.
mg twice daily for 7 days. After 3 days of treatment, pt. felt better
and discontinued further treatment deliberately. Few days later, she Counsel about referral, your limitations and bad prognosis.
again developed urgency, frequency of micturition and dysuria.
Do Urine C/S, renal function and other tests.
Urine C/S revealed same organism (sensitive to Nitrofurantoin).
Diet: CKD diet. Restrict fluid, protein and potassium.
Management
Drugs: 1. Either: Inj. Ceftron 1g 1 vial IV stat and BD until afebrile for
Ask necessary questions and give advice***
24 - 48 hrs (max. 14 days) followed by one of
Diet: Plenty of fluid (>2 L/day).
Tab. Levoxin 250 mg 1 tab stat then 250 mg ½ + 0 + 0 for rest of 14
Drugs: Cap. Nintoin SR 100 1 + 0 + 1 for 4 weeks days or

Example 12 – Acute cystitis in female with renal impairment: A 57 y Tab. Ciprocin 250 1 + 0 + 1 for rest of 14 days
old menopausal female with CKD stage IIIB (eGFR = 40 mL/min)
Or: Inj. Ceftron 1g 1 vial IV stat and BD for 14 days plus
presents with features of cystitis.
Inj. Levoxin 250 mg 1 bottle IV stat, then ½ bottle daily for 14 days.
Management
2. Inj. Anadol 100 mg ½ amp. IM 12 hrly and SOS
Ask necessary questions and give advice***
3. Inj. Emistat 8 mg 1 vial IV 8 hrly and SOS
Do Urine C/S (and other tests).
(Give drug according to C/S)
14. 1ST LINE DRUG TREATMENT FOR DIFFERENT UTIs

*Choose any 1 from drug treatment column until otherwise stated, drugs are oral until otherwise stated.

Duration
Name of the condition Drug treatment* Comments
Female Male
Acute uncomplicated Co – trimoxazole 960 mg 3 days 7 – 14 days Frequency, urgency,
cystitis (DS) BD dysuria, suprapubic pain,
Nitrofurantoin 100 mg SR 5 – 7 days 7 – 14 days stranguary, cloudy urine
BD
Fosfomycin 3 g Once every 3 days for 9 days
Complicated cystitis Levofloxacin 500 mg OD 7 – 10 days 7 – 14 days
Ciprofloxacin 250 mg BD 7 – 10 days 7 – 14 days
Acute pyelonephritis Ciprofloxacin 500 mg BD 14 days Fever, Flank pain, chills,
(Non – hospitalised) Levofloxacin 750 mg OD 7 – 14 days rigors, renal angle
Pyelonephritis Ceftriaxone IV 1 g BD 14 days tenderness
(hospitalised)
Recurrent UTI (related to Co – trimoxazole 480 mg each dose after intercourse Give advice. Find out cause.
sexual activity) Nitrofurantoin 50 mg
Recurrent UTI (unrelated Nitrofurantoin 50 mg 1 drug 1 dose every night for 1 month, then Give advice
to sexual activity) Cefalexin 250 mg another drug 1 dose each night for next month. Drugs rotate to prevent
Co – trimoxazole 480 mg (2/3 drugs in sequence, rotating every 6 months) resistance.
Amoxicillin 250 mg
Relapse UTI sensitive drug 2 – 4 weeks Pathogen not eradicated
before
Catheter – related UTI sensitive drug 7 – 10 days Prevention is best, don’t
treat all.
Asymptomatic sensitive drug 7 – 10 days Don’t treat all.
bacteriuria
Asymptomatic Nitrofurantoin 100 mg SR 7 days Avoid sulfonamides,
bacteriuria or cystitis in BD fluoroquinolones in
pregnancy Cefalexin 500 mg BD 7 days pregnancy
Pyelonephritis in Ceftriaxone 1g IV daily IV : up to 24 – 48 hours after fever subsides, then
pregnancy FOLLOWED BY oral = total 14 days
sensitive oral drug
Recurrent UTI in Cefalexin 500 mg after each remainder of the pregnancy
pregnancy intercourse AND/OR
Cefalexin 500 mg 1 drug 1 dose every night for 1 month, then next
Nitrofurantoin 100 mg drug 1 dose every night for next month. Alternate
between the 2 drugs monthly for remainder of the
pregnancy.
Overactive bladder/ Tolterodine 2 mg BD As needed Exclude UTI
detrusor hyperreflexia Solifenacin 10 mg OD
Mirabegron 25 – 50 mg OD up to 8 weeks/as needed
DS = double strength, BD = twice daily, OD = once daily, SR = sustained release, IV = intravenous

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