ISSUES IN INFECTION
Educational Objectives
The goals of this program are to improve the management of urinary tract infections (UTIs) and sexually transmitted diseases
(STDs), and assess the use of circumcision in the prevention of HIV infection. After hearing and assimilating this program,
the clinician will be better able to:
 | 1. Describe the mechanisms of UTI.
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| 2. Review the treatment of cystitis and pyelonephritis.
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| 3. Manage patients with prostatitis and chronic pelvic pain syndromes.
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| 4. Explain the role of the urologist in the management of STDs.
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| 5. Examine the evidence for use of circumcision in the prevention of HIV infection.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported
nothing to disclose.
Acknowledgements
Dr. Hafez gave his lecture at Updates in Urological Health: Advanced Diagnosis and Treatment of Urological Disorders,
presented November 10, 2007, in Dearborn, MI, by the Urology Center of the University of Michigan Medical
School. Dr. Krieger addressed Urology Update 2007: New Ideas, Approaches, and Techniques, presented October
26-27, 2007, by the University of Toronto, Department of Surgery, Urology Division. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
Urinary Tract Infections: A Management Overview
Khaled S. Hafez, MD, Assistant Professor, Department of Urology, University of Michigan Health System, Ann Arbor
Mechanisms of Urinary Tract Infection (UTI)
| Cystitis: bacteria colonize introitus of vagina and ascend to bladder via urethra; normal vaginal flora (eg, Lactobacillus)
compete with other bacteria (eg, Escherichia coli) that can cause UTI; lactobacilli also maintain acidity of vagina, inhibiting
growth of E coli; vaginal fluid influences bacterial adhesion because of its high level of secretory IgA; eliminating
bacteria from bladder—mechanical clearance by voiding; acid pH of urine; salts and lactoferrin in urine inhibit
and kill bacteria; inhibition of bacterial attachment by Tamm-Horsfall mucoprotein; antibodies, cytokines, and polymorphonuclear
(PMN) cells in bladder; exfoliation of infected epithelial cells; common pathogens—E coli most common
organism causing uncomplicated cystitis (≈80% of cases); Staphylococcus saprophyticus next most common in
young women (≈10%); others, eg, Enterococcus, Klebsiella, Proteus, any gram-negative organism
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| Risk factors: genetics, eg, urothelium of people with certain blood group antigens binds E coli more easily; menopause
and spermicides (change vaginal pH); intercourse; overuse of antibiotics, especially β-lactams (change vaginal flora);
instrumentation or catheterization; voiding dysfunction; immunosuppression; diabetes
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Treatment
| Uncomplicated cystitis: traditional definition of UTI >100 000 colony-forming units (CFU)/mL of urine; trimethoprim-
sulfamethoxazole (TMP-SMZ; eg, Bactrim) first choice; in areas of known resistance, use nitrofurantoin or fluoroquinolone;
ampicillin not used because more likely to disrupt normal flora and has high rate of resistance; treat uncomplicated
cystitis for 3 days; cases in which treatment for 7 days recommended include, if nitrofurantoin used, if symptoms
persist after 3 days, in recurrent UTI, in older patients, and in those who use diaphragms; refer to urologist if patient
has—recurrent UTI with same bacteria; voiding symptoms even without infection; certain organisms, eg, Proteus, which
may indicate stones or complicated anatomic problem in kidney; change from cystitis to pyelonephritis (presence of fever);
suspicion of colovesical fistula; nematuria or fecaluria
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| Recurrent cystitis: determine cause (eg, use of spermicides) and discontinue; topical estrogen for postmenopausal women;
postcoital antibiotics (single pill); continuous low-dose antibiotics, eg, one-half single-strength tablet of nitrofurantoin;
intermittent stop-start therapy—woman initiates self-treatment at first sign of symptom recurrence; nonantibiotic
treatment—eg, methenamine (mandelic acid), cranberry juice
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| Complicated cystitis: fluoroquinolones first-line therapy; use for ≥7 days
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| Pyelonephritis: usually bacteria ascend from infected bladder; hematogenous spread uncommon; risk factors—same as
for cystitis; P pili help bacteria attach to ureter; reflux; ureteral stasis; abnormal peristalsis in ureter; evaluation—
history; physical examination; urinalysis; ultrasonography (US); computed tomography (CT; normal in 75% of patients);
imaging especially indicated in patients with history of stones, genitourinary (GU) abnormality; ureteropelvic
junction obstruction, sepsis, continued fever and symptoms after 72 hr of antibiotic therapy
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| Outpatient treatment: strict criteria include healthy nonpregnant nonseptic women who are compliant and reliable for follow-up;
use oral antibiotics and increased fluid intake; treat with fluoroquinolone for 2 wk (moderate evidence for 7
days and TMP-SMZ); nitrofurantoin not used because of lack of tissue penetration; send specimen for culture, confirm
sensitivity, and complete 14 days of antibiotic
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| Inpatient treatment: IV broad-spectrum antibiotic, eg, fluoroquinolone, ampicillin plus gentamicin, third-generation
cephalosporin with or without aminoglycoside; convert to oral antibiotics once patient afebrile and doing better; treat
for 10 to 14 days; if fever persists or patient has complicated pyelonephritis, treat ≤3 wk
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| Infrequent subtypes: emphysematous pyelonephritis—urologic emergency; acute necrotizing parenchymal and perinephric
infection; usually caused by gas-forming organisms (E coli most common; Klebsiella and Proteus less common);
patients usually diabetic; intravenous pyelography (IVP) contraindicated; CT or US plus kidney-ureter-bladder (KUB)
film; start IV antibiotics and fluids; emergent nephrectomy or emergent percutaneous drainage; xanthogranulomatous
pyelonephritis (XGP)—rare severe chronic infection of kidney, with accumulation of lipid-laden foaming macrophages;
unilateral large kidney seems cancerous but usually not; usually stone in renal pelvis; kidney nonfunctional or poorly
functioning; Proteus most common pathogen, followed by E coli; treat with antibiotics and surgery, usually nephrectomy
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| Asymptomatic bacteriuria: incidence—≈5% in young women, higher in older women; high in patients with catheter,
stone, or other UT obstruction; treatment—no benefit in nonpregnant women, diabetics, elderly patients, or those with
long-term catheter use (treat only if symptomatic); treat pregnant women, and patients with stones, obstruction, GU abnormalities,
and those preparing for procedure; pregnant women—treatment indicated to prevent pyelonephritis (develops
in approximately one-third of patients; can lead to sepsis in mother and prematurity; group B streptococci transmitted
to newborn can cause sepsis, pneumonia, meningitis, and possibly death; diagnosis—clean catch urine at first prenatal
visit; if positive, give 3 to 7 days of antibiotics; reculture 10 days later and throughout pregnancy
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| Cystitis in pregnancy: 3 to 7 days of treatment (ampicillin and aminoglycosides safe in pregnancy); reculture after treatment;
admit if pyelonephritis develops; oral antibiotics for 10 to 14 days once patient improves; suppressive therapy throughout pregnancy
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Prostatitis and Chronic Pelvic Pain Syndromes
| Acute bacterial prostatitis (category 1): usually caused by E coli, Enterococcus, Pseudomonas, Enterobacter, or Klebsiella
; reflux of urine and bacteria into prostatic duct; risk factors—UTI; condom catheter or indwelling catheter; recent
transurethral surgery; symptoms—acute onset of perineal pain associated with urinary symptoms (usually obstructive); if
not detected early, fever, chills, malaise, and nausea; physical examination—boggy hot tender prostate (do not massage);
urinalysis and culture mandatory; unlike chronic prostatitis, most antibiotics enter prostate; ampicillin and gentamicin
first choice, third-generation cephalosporin second choice; fluoroquinolones also used; after acute phase, TMZ-SMZ or
fluoroquinolone for 4 wk; if no improvement, obtain transvesical US to rule out abscess; place small Foley catheter if patient
cannot void (suprapubic catheter also used); patients usually constipated and need stool softeners
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| Chronic prostatitis syndromes: category 2 chronic bacterial prostatitis; category 3 chronic pelvic pain syndromes; symptoms
similar; diagnosis—4-glass test (seldom used); 2-glass test consists of midstream urine before prostatic massage,
and first 10 mL of urine after massage; if both specimens positive, presume prostatitis and treat empirically with nitrofurantoin;
if post-massage specimen negative, diagnosis category 2 chronic bacterial prostatitis; if both specimens negative,
category 3 chronic pelvic pain syndrome; if white blood cells (WBCs) in post-massage specimen, category 3A,
ie, inflammatory; if no WBCs in post-massage fluid, category 3B, ie, noninflammatory
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| Category 2: determine American Urological Association (AUA) symptom score; prostate usually normal size and not
tender; check other potential pain sites (eg, perineum, groin, coccyx); urinalysis, culture, and 2-glass test; uroflow and
postvoid residual measurement recommended; treatment—1 to 3 mo of antibiotics, eg, TMP-SMZ, fluoroquinolone;
no evidence for repeating prostatic massage; for recurrent episodes, perform transurethral US of prostate to look for anatomic
abnormality; transurethral resection of prostate (TURP) does not help
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| Category 3: GU pain in absence of bacteria; evaluation same as for category 2; all drugs used (eg, α-blockers) off-label;
most treatments do not distinguish between categories 3A and 3B (outcomes similar); 3B may be due to bladder neck
obstruction (rule out with urodynamic study); other treatments include physical therapy of pelvic floor, muscle relaxants,
prostatic massage, and psychologic support; surgery if indicated
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| Category 4: asymptomatic patient with WBCs and/or bacteria in prostatic fluid; no treatment unless patient being prepared
for surgery, prostate-specific antigen (PSA) elevated, or infection present and contributing to infertility
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Fungal UTI
| Risk factors: indwelling catheter; abuse of antibiotics; diabetes; malignancy; steroids; anatomic anomaly
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| Treatment: Candida commonest cause; remove catheter; stop antibiotics; improve nutrition; if patient in intensive care
unit (ICU), controversial whether to treat even if asymptomatic (high risk for invasive candidal infection in ICU); treat
skin infections with topical agents or single oral dose of fluconazole; for candidal cystitis, oral or IV fluconazole; in ICU,
irrigation with amphotericin B, 50 mg/L, 42 mL/hr, 1 L/day
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| Upper tract infections: aggressive treatment with amphotericin B; imaging to look for fungus balls; if found, drainage and amphotericin
irrigation of kidney indicated, as is systemic IV amphotericin; digital rectal examination mandatory to look for abscess
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Sexually Transmitted Diseases
| Male urethritis: symptoms dysuria, urethral itch, and discharge; Neisseria gonorrhoeae and Chlamydia most common
causes; diagnostic tests—nucleic acid amplification on urine; older method microscopic examination of urethral swab
for intracellular diplococci (N gonorrhoeae); if WBCs seen without diplococci, diagnosis Chlamydia; evaluate and treat
all partners exposed in previous 60 days; treatment 1 IM dose ceftriaxone 125 mg; add 1 g azithromycin, since 30% of
patients also have Chlamydia; quinolones alternative, except in areas with known resistance; for nongonococcal urethritis,
azithromycin covers Chlamydia and Ureaplasma
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Genital Ulcers
| Herpes simplex virus (HSV) type 2: pain, itching, dysuria, and urethral discharge; vesicles that coalesce to form tender ulcers;
diagnosed by smear showing intranuclear inclusions, by immunofluorescence, or by viral culture (most sensitive);
treatment—IV or oral acyclovir decreases duration of shedding and crusting; 6 to 8 recurrences per year (if more, acyclovir
prophylaxis recommended); counsel patients to—expect recurrences; decrease transmission by abstinence during
symptoms; use condoms
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| Chancroid: painful ulcer caused by Haemophilus ducreyi; deep undermined border, friable and necrotic; associated with
lymphadenopathy in ≈50% of cases; diagnose by Gram stain of ulcer base and culture; treat patient and partner with
azithromycin or ceftriaxone (1 dose) or erythromycin (1 wk)
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| Syphilis: 4-wk incubation period; in primary syphilis, chancre painless and lymph nodes rubbery and painless; diagnosis by
dark-field microscopy of ulcer scrapings; nontreponemal antibody test indicates disease activity; treponemal antibody
tests do not correlate with disease activity and once positive, remain positive; treat with benzathine penicillin G 2.4 million
U IM (one dose; desensitize penicillin-allergic patients); alternatively, doxycycline or tetracycline for 2 wk; Jarisch-
Herxheimer reaction occurs in ≤50% of patients; check for HIV
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| Chlamydia: most common STD in industrialized nations; clinical manifestations urethritis, epididymitis, and balanitis; diagnose
by cytoplasmic inclusions seen with special stains; treat with doxycycline 100 mg bid for 1 wk; single-dose
azithromycin commonly used, also erythromycin 250 mg q6h for 2 wk
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| Trichomonas vaginalis: ≤50% asymptomatic; symptoms burning, itching, discharge, and dyspareunia; discharge frothy
and yellow-to-green, with pH of 6.5 and fishy odor; clue cells seen on microscopy; treat with oral metronidazole (eg,
Flagyl) 2-g single dose (contraindicated in pregnancy; use vaginal suppositories); partner treatment controversial
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Other Sexually Transmitted Infections
| Genital warts (condyloma acuminata): treat by removing lesions (does not eradicate disease); remove external lesions
with podophyllin, cryotherapy, or laser therapy; remove urethral lesions with laser or 5% 5-fluorouracil
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| AIDS: urologic manifestations include opportunistic infections, fungi, HSV, viral cystitis, testis cancer, renal cell cancer,
hypogonadism, neurogenic bladder, nephropathy, and hyponatremia; stones related to treatment (eg, indinavir stones) not
seen on CT; best to stop treatment and hydrate with or without urinary acidification
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Does Circumcision Reduce the Risk for HIV Infection?
John N. Krieger, MD, Professor of Urology, University of Washington School of Medicine, Seattle
Epidemiologic Studies
| Ecologic studies: look at regional prevalence; in 1980, Africa “checkerboard” with widely varying rates of HIV infection;
in general population, proportion of HIV infection goes down as proportion of circumcised men goes up; same pattern in
Asia and North America; countries where fewer than 1 in 5 men circumcised have much higher prevalence of HIV infection
than countries where ≥80% of men circumcised
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| Observational studies: look at prevalence within society; ≈40 studies looking at one point in time or following population
over time; significant protection in 28 studies from 8 countries, and trend in 5 studies; seroprevalence up to 30%
in some areas, as low as 8% in other areas; multivariate analysis found circumcision associated with 400% decrease in
HIV risk
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| Prospective studies: India (1 study)—700 men; only 7% circumcised; risk ratio 3, ie, circumcised men at one-third risk;
United States (3 studies)—consistently showed 350% higher risk for HIV infection in uncircumcised men (after adjustment
for sexual behavior and other variables); Africa (5 studies)—high-risk populations; risk for infection up to
800% higher for uncircumcised men; discordant couples (woman infected)—if man uncircumcised, 40 of 137 seroconverted;
for circumcised men, seroconversion rate zero
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| Combined analysis of 27 studies from 8 countries: circumcised men at 50% risk for HIV infection; after adjustments for
sexual behaviors and other variables, risk 40%; as risk increases, protection afforded by circumcision increases
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| Confounding variables: international health authorities argued that difference could be due to more STDs and inflammation
in uncircumcised men, as well as behavioral, hygienic, and cultural differences; tears during sex more common in
uncircumcised men; 7-fold increase in number of HIV receptors on inner side of foreskin, and more receptors in men
with recent infection
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| Kenyan trial of circumcision in adult men: one of 3 randomized clinical trials in Africa; 25% of general population HIV
positive; 5% of 18-yr-olds, 24% in 25-yr-olds; 7000 men screened and randomized to receive circumcision or no circumcision
and followed every 6 mo for 2 yr; given unlimited condoms, counseling, and testing; results—study
stopped at 90% of completion so that circumcision could be offered to controls; median follow-up 24 mo
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| Summary: seroconversion rate twice as high in controls; 96% adherence to treatment; by intent-to treat analysis, circumcision
reduced HIV infection by 53%; by as-treated analysis, circumcision reduced HIV infection by 60%
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Suggested Reading
Baeten JM et al: Female-to-male infectivity of HIV-1 among circumcised and uncircumcised Kenyan men. J Infect Dis 191:546,
2005; Bailey RC et al: Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet
369:643, 2007; Benway BM et al: Bacterial prostatitis. Urol Clin North Am 35:23, 2008; Frenkl TL et al: Sexually transmitted
infections. Urol Clin North Am 35:33, 2008; Gopal M et al: Clinical symptoms predictive of recurrent urinary tract
infections. Am J Obstet Gynecol 197:74, 2007; e1-4.Gray RH et al: Male circumcision for HIV prevention in men in Rakai,
Uganda: a randomised trial. Lancet 369:657, 2007; Grupper M et al: Emphysematous cystitis: illustrative case report and review
of the literature. Medicine (Baltimore) 86:47, 2007; Gupta K et al: Short-course nitrofurantoin for the treatment of acute uncomplicated
cystitis in women. Arch Intern Med 167:2207, 2007; Hsu CY et al: The clinical impact of bacteremia in complicated acute
pyelonephritis. Am J Med Sci 332:175, 2006; Katchman EA et al: Three-day vs longer duration of antibiotic treatment for cystitis
in women: systematic review and meta-analysis. Am J Med 118:1196, 2005 ; Macejko AM et al: Asymptomatic bacteriuria and
symptomatic urinary tract infections during pregnancy. Urol Clin North Am 34:35, 2007; Nicolle LE: Uncomplicated urinary tract
infection in adults including uncomplicated pyelonephritis. Urol Clin North Am 35:1, 2008; Padian NS et al: Biomedical interventions
to prevent HIV infection: evidence, challenges, and way forward. Lancet 372:585, 2008; Pontari MA: Chronic prostatitis/
chronic pelvic pain syndrome. Urol Clin North Am 35:81, 2008; Reynolds SJ et al: Male circumcision and risk of HIV-1 and
other sexually transmitted infections in India. Lancet 363:1039, 2004; Soto SM et al: Biofilm formation in uropathogenic Escherichia
coli strains: relationship with prostatitis, urovirulence factors and antimicrobial resistance. J Urol 177:365, 2007; Stapleton A:
Urinary tract infections in patients with diabetes. Am J Med 113 Suppl 1A:80S, 2002.
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