Pharmacotherapy

Urinary Tract
Infection
Yuani Setiawati, dr., MKed
• A urinary tract infection (UTI) is defined as the
presence of microorganisms in the urine that
cannot be accounted for by contamination. The
organisms have the potential to invade the tissues
of the urinary tract and adjacent structures.
 Site of Infection
• Lower tract infections include cystitis (bladder),
urethritis (urethra), prostatitis (prostate gland),
and epididymitis.

• Upper tract infections (such as pyelonephritis)

involve the kidney and are referred to as
pyelonephritis.
 Stage of Complication
• Uncomplicated UTIs are not associated with
structural or neurologic abnormalities that may
interfere with the normal flow of urine or the voiding
mechanism.

• Complicated UTIs are the result of a predisposing

lesion of the urinary tract such as a congenital
abnormality or distortion of the urinary tract, a
stone, indwelling catheter, prostatic hypertrophy,
obstruction, or neurologic deficit that interferes with
the normal flow of urine and urinary tract defenses
 Definition
• Recurrent UTIs = characterized by multiple symptomatic
episodes with asymptomatic periods occurring between
these episodes.
These infections are either due to reinfection or to relapse.

• Reinfections = caused by a different organism & account for

the majority of recurrent UTIs.
Usually happens > 2 weeks after the last UTI
Treated as a new uncomplicated UTI.

• Relapse = the development of repeated infections caused

by the same initial organism.
Usually happens within 2 weeks of the original infection
A relapse of the original infection
Because of unsuccessful treatment of the original infection,
a resistant organism, or anatomical abnormalities.
 SYMPTOMS
• Lower urinary tract infections: dysuria,
urgency, frequency, nocturia, and
suprapubic heaviness,

• Upper urinary tract infections: more systemic

symptoms such as fever, nausea, vomiting,
and flank pain.
 ETIOLOGY
• The bacteria usually originate from bowel flora of the host.

• Every organism can associated with UTIs but certain organisms

predominate as a result of specific virulence fc.

• Over 95% Uncomplicated urinary tract infections are the result

of a single causative organism :
o E. coli (85 %)
o G(+): S. saprophyticus (5-15%), Enterococcus spp. (5-10%)
o G(-): K. pneumoniae, Proteus spp., P. aeruginosa &
Enterobacter spp
o Because S. epidermidis is frequently isolated from the
urinary tract à considered initially a contaminant.

• Complicated infections are more frequently associated with

gram(-) organisms & Enterococcus faecalis à
• This finding may be related to the extensive use of
third- generation cephalosporin antibiotics, which are
not active against the enterococci.
• Vancomycin-resistant Enterococcus faecalis &
Enterococcus faecium (Vancomycin-resistant
enterococci) have become more widespread,
especially in patients with long-term hospitalizations
or underlying malignancies. Vancomycin-resistant
enterococci are major therapeutic & infection control
issues because the organisms are susceptible to few
antimicrobials.
• S. aureus infections may arise from the urinary tract,
but they are more commonly a result of bacteremia
producing metastatic abscesses in the kidney.
• Candida spp. are common causes of UTI in the
critically ill and chronically catheterized patient.
• Most UTIs are caused by a single organism; however, in
patients with stones, indwelling urinary catheters, or chronic
renal abscesses, multiple organisms may be isolated.

• Organisms isolated from individuals with recurrent UTIs,

particularly complicated infections are more varied &
generally are more resistant
o E. coli is a frequently isolated pathogen (< 50%)
o Other frequently isolated organisms include Proteus spp.,
K. pneumoniae, Enterobacter spp., P. aeruginosa,
Staphylococci & Enterococci
o Enterococci represent the second most frequently
isolated organisms in hospitalized patients.

• It is also more common for organisms other than E. coli to

cause UTIs in the hospitalized population.
• The etiology of UTIs has unchanged over the past
several decades. The frequency of causative
organisms changes depending on whether the setting
is a complicated or uncomplicated UTI.

• There is a lack of consensus regarding the definition

of what makes a UTI complicated, but in general a
complicated UTI refers to a structural or functional
abnormality of the urinary tract.

• Patients with complicated UTIs are typically given

longer treatment durations than uncomplicated. Those
with complicated UTIs by definition are also prone to
more frequent infections.

• It is important to note that an upper UTI does not

necessarily imply complicated UTI, nor does lower UTI
imply uncomplicated UTI.
 PHARMACOTHERAPY

• DESIRED OUTCOME
The goals of treatment for UTIs :
Øprevent or treat systemic consequences of
infection
Øeradicate the invading organism
Øprevent recurrence of infection
• GENERAL PRINCIPLES
o The management of a patient with a UTI :
Øinitial evaluation
Øselection of an antibacterial agent & duration of
therapy
Øfollow-up evaluation

o The initial selection of an antimicrobial agent for

the treatment of UTI is primarily based on:
Øthe severity of the presenting signs & symptoms
Øthe site of infection
Øwhether the infection is determined to be
complicated or uncomplicated
o PHARMACOLOGIC TREATMENT
• The ability to eradicate bacteria from the urinary
tract is directly related to the sensitivity of the
organism & the achievable concentration of the
antimicrobial agent in the urine.
• The therapeutic management of UTIs is best
accomplished by first categorizing the type of
infection: acute uncomplicated cystitis,
symptomatic abacteriuria, asymptomatic
bacteriuria, complicated UTIs, recurrent infections,
or prostatitis.
• Table 76.2 gives the most common agents used in
the treatment of UTIs, along with comments
concerning their general use.
• Antimicrobial therapy is the cornerstone of treatment in
UTIs:
Ø ideally be well tolerated
Ø narrow in antimicrobial spectrum,
Ø lend itself to patient compliance (taken as infrequently as
possible)
Ø have adequate concentrations at the site of the infection
Ø have good oral bioavailability.
• Uncomplicated urinary tract infections can be managed
most effectively with short-course (3 days) therapy with
either trimethoprim-sulfamethoxazole or a fluoroquinolone.
• Complicated infections require longer treatment periods (2
weeks) usually with one of these agents.
• In choosing appropriate antibiotic therapy, practitioners need
to be cognizant of antibiotic resistance patterns, particularly
to E. coli. Trimethoprim-sulfamethoxazole has demonstrated
diminished activity against E. coli in some areas of the
country (resistance up to 20%)
 Uncomplicated Cystitis
• Represents the most common of UTIs.
• Frequently managed in the outpatient setting &
occur in women of childbearing age.
• E. coli is the most frequent (85%) of causal but in a
minority of cases may be caused by S.
saprophyticus, K. pneumoniae, P. mirabilis,
Enterococcus spp., & a small percentage of others.
• Because the causative organisms & their
susceptibilities are generally known, a cost-effective
approach to management & treatment in the
outpatient is recommended that includes a
urinalysis and initiation of empiric therapy without a
urine culture
• One significant benefit of treatment is the duration
can be < 7 days (often 3 days or even 1 day)

• Although treatment duration of 1 day is

advantageous because it strictly limits adverse
events & drug interactions & increases complianceà
practitioners should know that 3-day courses of
fluoroquinolones & trimethoprim-sulfamethoxazole
are superior to single-doses in terms of cure rates in
uncomplicated UTIs.

• Which agent to choose empirically partly hinges on

known resistance rates in the geographic region,
particularly E. coli resistance to trimethoprim-
sulfamethoxazole.
•Although no consensus has been reached on what
percentage of E. coli isolates is resistant to
trimethoprim-sulfamethoxazole should preclude its
use, a model has recently been created that suggests
that this threshold should be 19%- 21% in the empiric
setting.

•Amoxicillin or sulfonamides are not recommended

because of the high incidence of resistant E. coli.

•Patients are subsequently followed-up for resolution

of signs and symptoms. Follow-up urine cultures are
not necessary in patients who respond.
Symptomatic Abacteriuria
• Single-dose or short-course therapy with
trimethoprim–sulfamethoxazole has been used
effectively, and prolonged courses of therapy are
not necessary for the majority of patients.

• If single-dose or short-course therapy is

ineffective, a culture should be obtained.

• If the patient reports recent sexual activity, therapy

for Chlamydia trachomatis should be considered
(azithromycin 1 g as a single dose or doxycycline
100 mg twice daily for 7 days).
 Asymptomatic Bacteriuria
§ The management depends on the age of the patient
and, if female, whether she is pregnant. In children,
treatment should consist of conventional courses of
therapy, as described for symptomatic infections.

§ In the nonpregnant female, therapy is controversial;

however, it appears that treatment has little effect on
the natural course of infections.

§ Most clinicians feel that asymptomatic bacteriuria in

the elderly is a benign disease and may not warrant
treatment. The presence of bacteriuria can be
confirmed by culture if treatment is considered.
 Acute Pyelonephritis
• In contrast to patients with lower tract UTIs,
pyelonephritis will have high-grade fever [ >38.3°C
(100.9°F)] & severe flank pain.

• Patient with mild cases of pyelonephritis (defined as

low-grade fever & a normal to slightly elevated
peripheral white blood cell count, without nausea or
vomiting) may be treated in the outpatient setting

• Patients whose infection is severe enough to cause

vomiting, decreased food intake & dehydration
should be treated in an inpatient hospitalized setting.
These patients will receive intravenous antibiotics at
first before being switched to oral therapy.
• Pyelonephritis are traditionally given 14 days of
therapy; however, there are limited data showing
success in treating acute uncomplicated
pyelonephritis for 7-10 days. More studies need to
be conducted on treating for these shorter durations.

• Patient who are treated in an outpatient setting can

be treated with trimethoprim-sulfamethoxazole,
fluoroquinolones, or even β-lactam/β-lactamase
inhibitors, such as amoxicillin-clavulanate.

• Patients that are admitted to the hospital, antibiotic

therapy is usually broader in nature, especially in
patients suspected of having bacteremia or
urosepsis. These patients will typically receive IV
therapy such as a fluoroquinolone, or a β-lactam plus
an aminoglycoside.
• The presentation of high-grade fever (>38.3°C
[100.9°F]) & severe flank pain should be treated as
acute pyelonephritis & aggressive management is
warranted.

• Severely ill patients with pyelonephritis should be

hospitalized and IV drugs administered initially.
Milder cases may be managed with oral antibiotics
in an outpatient setting.

• At the time of presentation, a Gram stain of the

urine should be performed, along with urinalysis,
culture, and sensitivities.
• In the mild- moderately symptomatic patient for
whom oral therapy is considered, an effective agent
should be administered for at least a 2-week period,
although use of highly active agents for 7 to 10 days
may be sufficient. Oral antibiotics that have shown
efficacy in this setting include trimethoprim–
sulfamethoxazole or fluoroquinolones. If a Gram
stain reveals gram-positive cocci, Streptococcus
faecalis should be considered and treatment directed
against this pathogen (ampicillin).

• In the seriously ill patient, the traditional initial therapy

has included an IV fluoroquinolone, an
aminoglycoside with or without ampicillin, or an
extended-spectrum cephalosporin with or without
an aminoglycoside.
• If the patient has been hospitalized in the last 6
months, has a urinary catheter, or is in a nursing
home, the possibility of P. aeruginosa & enterococci
infection, as well as multiply-resistant organisms,
should be considered. In this setting, ceftazidime,
ticarcillin-clavulanic acid, piperacillin,
aztreonam, meropenem, or imipenem, in
combination with an aminoglycoside, is
recommended. If the patient responds to initial
combination therapy, the aminoglycoside may be
discontinued after 3 days.

• Follow-up urine cultures should be obtained 2 week

after the completion of therapy to ensure a
satisfactory response and to detect possible relapse.
Urinary Tract Infections in Males
• The conventional view is that therapy in males
requires prolonged treatment

• A urine culture should be obtained before

treatment, because the cause of infection in men
is not as predictable as in women.

• If gram-negative bacteria are presumed,

trimethoprim–sulfamethoxazole or a
fluoroquinolone is a preferred agent. Initial
therapy is for 10 to 14 days.

• For recurrent infections in males, cure rates are

much higher with a 6-week regimen of
trimethoprim–sulfamethoxazole.
 Recurrent Infections
• Recurrent episodes of UTI (reinfections & relapses) account
for a significant portion of all UTIs.
• These patients are most commonly women & can be divided
into 2 groups: those with < 2-3 episodes/ year & those who
develop more frequent infections.
• In patients with infrequent infections (i.e., < 3
infections/year), each episode should be treated as a
separately occurring infection. Short-course therapy should
be used in symptomatic female patients with lower tract
infection.
• In patients who have frequent symptomatic infections, long-
term prophylactic antimicrobial therapy may be instituted
(see Table 50-4). Therapy is generally given for 6 months,
with urine cultures followed periodically.
• In women who experience symptomatic
reinfections in association with sexual activity,
voiding after intercourse may help prevent
infection. Also, self-administered, single-dose
prophylactic therapy with trimethoprim–
sulfamethoxazole taken after intercourse has
been found to significantly reduce the incidence of
recurrent infection in these patients.

• Women who relapse after short-course therapy

should receive a 2-week course of therapy. In
patients who relapse after 2 weeks, therapy should
be continued for another 2 to 4 weeks. If relapse
occurs after 6 weeks of treatment, urologic
examination should be performed, and therapy for
6 months or even longer may be considered.
Urinary Tract Infection in Pregnancy
o In patients with significant bacteriuria, symptomatic
or asymptomatic, treatment is recommended in
order to avoid possible complications during the
pregnancy. Therapy should consist of an agent with
a relatively low adverse-effect potential (a
sulfonamide, cephalexin, amoxicillin,
amoxicillin/clavulanate, nitrofurantoin)
administered for 7 days.
o Tetracyclines should be avoided because of
teratogenic effects & sulfonamides should not be
administered during the third trimester because of
the possible development of kernicterus &
hyperbilirubinemia. Also, the fluoroquinolones
should not be given because of their potential to
inhibit cartilage & bone development in the
newborn.
 Catheterized Patients
o When bacteriuria occurs in the asymptomatic, short-
term catheterized patient (< 30 days), the use of
systemic antibiotic therapy should be withheld and the
catheter removed as soon as possible. If the patient
becomes symptomatic, the catheter should again be
removed, and treatment as described for complicated
infections should be started.
o The use of prophylactic systemic antibiotics in patients
with short-term catheterization reduces the incidence
of infection over the first 4 to 7 days.
o In long-term catheterized patients, however, antibiotics
only postpone the development of bacteriuria and lead
to emergence of resistant organisms.
 GONORRHOE
• Neisseria gonorrhoeae is a gram-negative diplococcus
• Humans are the only known host of this intracellular
parasite.
• Infected individuals may be symptomatic or
asymptomatic, have complicated or uncomplicated
infections, and have infections involving several
anatomic sites.
• Approximately 15% of women with gonorrhea develop
pelvic inflammatory disease. Left untreated, pelvic
inflammatory disease can be an indirect cause of
infertility and ectopic pregnancies.
• In 0.5% to 3.0% of patients with gonorrhea, the
gonococci invade the bloodstream and produce
disseminated disease. The usual clinical mani-
festations of disseminated gonococcal infection are
tender necrotic skin lesions, tenosynovitis, and
monoarticular arthritis.
• Diagnosis of gonococcal infections can be
made by gram-stained smears, culture
(the most reliable method), or newer
methods based on the detection of cellular
components of the gonococcus (e.g.,
enzymes, anti- gens, DNA, or
lipopolysaccharide) in clinical specimens.
 TABLE 46-2 Selected Syndromes Associated with Common Sexually Transmitted Pathogens
Syndrome Commonly Implicated Pathogens Common Clinical Manifestationsa
Urethritis Chlamydia trachomatis, herpes simplex virus, Neisseria gonorrhoeae, Trichomonas Urethral discharge, dysuria
vaginalis, Ureaplasma urealyticum
Epididymitis C. trachomatis, N. gonorrhoeae Scrotal pain, inguinal pain, flank pain, urethral discharge
Cervicitis/vulvovaginitis C. trachomatis, Gardnerella vaginalis, herpes simplex virus, human papil omavirus, N. Abnormal vaginal discharge, vulvar itching/irritation, dysuria, dyspareunia
gonorrhoeae, T. vaginalis
Genital ulcers (painful) Haemophilus ducreyi, herpes simplex virus Usually multiple vesicular/pustular (herpes) or papular/pustular (H. ducreyi) lesions that may
coalesce; painful, tender lymphadenopathy b
Genital ulcers (painless) Treponema pallidum Usually single papular lesion
Genital/anal warts Human papil omavirus Multiple lesions ranging in size from small papular warts to large exophytic condylomas
Pharyngitis C. trachomatis (?), herpes simplex virus, N. gonorrhoeae Symptoms of acute pharyngitis, cervical lymphadenopathy, fever c
Proctitis C. trachomatis, herpes simplex virus, N. gonorrhoeae, T. pallidum Constipation, anorectal discomfort, tenesmus, mucopurulent rectal discharge
Salpingitis C. trachomatis, N. gonorrhoeae Lower abdominal pain, purulent cervical or vaginal discharge, adnexal swelling, fever d
aFor some syndromes, clinical manifestations may be minimal or absent.
bRecurrent herpes infection may manifest as a single lesion.
cMost cases of pharyngeal gonococcal infection are asymptomatic.
dSalpingitis increases the risk of subsequent ectopic pregnancy and infertility.
 PHARMACOTHERAPY GO
• All recommended regimens are single-dose with various
oral or parenteral cephalosporins & fluoroquinolones.

• Ceftriaxone is the only parenteral agent recommended

by the CDC as a first-line agent for treatment.

• Coexisting chlamydial infection, which is documented in

up to 50% of women & 20% of men with gonorrhea,
constitutes the major cause of postgonococcal urethritis,
cervicitis & salpingitis in patients treated for gonorrheaà
concomitant treatment with doxycycline or
azithromycin is recommended in all patients treated for
gonorrhea. A single dose of azithromycin (2 g) or
amoxicillin is highly effective against Chlamydia
trachomatis infection.
• Pregnant women with GO should be treated with
either a cephalosporin or spectinomycin,
because fluoroquinolones are contra indication.

• Treatment of gonorrhea during pregnancy is

essential to prevent ophthalmia neonatorum.
The CDC recommends that either tetracycline
(1%) ophthalmic ointment or erythromycin
(0.5%) ophthalmic ointment be instilled in each
conjunctival sac immediately postpartum to
prevent ophthalmia neonatorum.
THANK YOU