Genitourinary Tract Infections (UTI) - Comprehensive Chapter

1. DEFINITIONS

• Harrison's Principles 22E, p. 1130
• Comprehensive Clinical Nephrology 7E, p. 530
• Bailey & Love's Surgery 28E, p. 1532

2. EPIDEMIOLOGY

• UTI is one of the leading reasons antibiotics are prescribed worldwide.
• Half of all women experience a UTI in their lifetime; up to 50% will have recurrent infection within 6 months.
• The highest incidence of pyelonephritis is in women aged 20-30 years.
• Pyelonephritis requires hospitalization in up to 20% of non-pregnant women.
• ASB affects 2-9% of all pregnant women and up to 30% may develop pyelonephritis if untreated.
• The ratio of pyelonephritis to cystitis episodes is approximately 1:18 to 1:29.
• Cystitis in men is uncommon except with catheterization, instrumentation, or prostatic hypertrophy.
• In spinal cord injury (SCI) patients, UTI occurred in 100% of patients in one 40-50 year follow-up study.
• Brenner & Rector's The Kidney, p. 4483
• Comprehensive Clinical Nephrology 7E, p. 4250
• Campbell-Walsh-Wein Urology, p. 3437

3. CLASSIFICATION

• Uncomplicated - healthy patient, structurally/functionally normal urinary tract
• Complicated - anatomical or functional abnormality, immunocompromised host, more virulent/resistant bacteria

4. PATHOGENESIS

4a. Routes of Infection

1. Ascending (most common): Uropathogenic organisms from the GI tract contaminate the vaginal/periurethral area, adhere, and migrate into the urethra and bladder.
2. Haematogenous (less common): Seen with Staphylococcus aureus and fungal infections (particularly candiduria).
3. Direct spread: From retroperitoneal abscess or inflammatory bowel disease (rare).

• Bailey & Love 28E, p. 1532

4b. Environmental Factors (Harrison's 22E, p. 1131)

• Vaginal ecology: Colonization of vaginal introitus with intestinal flora (usually E. coli) is the critical initial step. Sexual intercourse increases this risk.
• Spermicide (nonoxynol-9): Toxic to vaginal lactobacilli, increases risk of E. coli bacteriuria.
• Postmenopausal: Lactobacilli replaced by Gram-negative bacteria due to vaginal atrophy; topical estrogens reduce recurrent UTI frequency.
• Anatomic/functional abnormalities: Urinary stasis or obstruction (stones, catheters, prostatic hypertrophy, neurogenic bladder, vesicoureteral reflux) all increase risk.

4c. Host (Genetic) Factors

• Familial disposition to UTI is well documented in women.
• First UTI before age 15 and maternal history of UTI are strong predictors.
• Women with recurrent UTI bind uropathogenic bacteria 3-fold more than women without - partly from not expressing certain blood group antigens.
• Mutations in Toll-like receptors and IL-8 receptor genes linked to recurrent UTI and pyelonephritis.

4d. Bacterial Virulence Factors

• Bailey & Love 28E, p. 1532
• P fimbria (Pap): Produce adhesin Gal(alpha1-4)Gal beta disaccharide (galobiosse) - directly induces mucosal inflammation and plays key role in pyelonephritis pathogenesis.
• Type 1 fimbriae (FimH): Mediate attachment to uroplakin receptors on urothelial cells.

5. MICROBIOLOGY / CAUSATIVE ORGANISMS

Uncomplicated UTI:

• E. coli - 85% of infections (dominant pathogen)
• Staphylococcus saprophyticus (particularly in young sexually active women)
• Enterococcus faecalis
• Proteus mirabilis
• Klebsiella pneumoniae

Complicated UTI:

• E. coli - 50%
• Enterococci
• Staphylococcus aureus
• Pseudomonas aeruginosa
• (Plus Klebsiella, Proteus, Enterobacter)

Organisms in Pregnancy (Comprehensive Clinical Nephrology 7E, Box 44.1):

• E. coli (>70%)
• Klebsiella spp.
• Proteus spp. (particularly in diabetics or urinary obstruction)
• Enterococci
• Staphylococci, especially S. saprophyticus
• Pseudomonas

Special notes:

• Candida: Haematogenous route more common; candiduria in catheterized patients usually follows antimicrobial therapy.
• Pseudomonas UTI: Almost always complicated; associated with catheters, stents, or stones.

6. CLINICAL FEATURES

Cystitis:

• Dysuria, suprapubic pain, urinary frequency and urgency
• Haematuria (present in ~30% on microscopy)
• Strangury
• No systemic features

Pyelonephritis:

• Fever (key distinguishing feature from cystitis), rigors
• Flank/loin pain, costovertebral angle tenderness
• Nausea, vomiting
• Lower urinary tract symptoms may or may not precede

Prostatitis (Harrison's 22E, p. 1132):

• Acute bacterial prostatitis (ABP): Dysuria, frequency, perineal/pelvic pain; can be severe with fever, rigors, bladder outlet obstruction.
• Chronic bacterial prostatitis (CBP): Recurrent cystitis episodes, pelvic/perineal pain; no systemic signs; often evaluated as outpatient.

Cystitis in Men:

• Similar symptoms to women.
• Approach with caution; exclude ABP, CBP, pyelonephritis before diagnosing cystitis.
• Urine cultures mandatory in all male UTI cases.
• Features of febrile UTI in men predictive of surgically correctable disorders: urinary retention, early recurrence, hematuria at follow-up, voiding difficulties.

7. DIAGNOSIS

Urinalysis & Dipstick:

• Nitrite: Only Enterobacterales convert nitrate to nitrite. False-negative if non-Enterobacterales, or if frequent voiding prevents nitrite accumulation.
• Leukocyte esterase: Surrogate for pyuria; detects enzyme in neutrophils (intact or lysed).
• A dipstick negative for both nitrite and leukocyte esterase should prompt consideration of alternative diagnoses.
• Negative dipstick does NOT rule out bacteriuria in pregnant women - culture is mandatory.

Urine Microscopy:

• Pyuria: classically >10 WBC/HPF; however modern data suggest >250 WBC/HPF may better correlate with symptoms in older women.
• Haematuria in ~30% of cystitis.

Urine Culture:

• Colony count threshold: >10^2 bacteria/mL is more sensitive (95%) for acute cystitis in women than the traditional >10^5/mL.
• Traditional >10^5/mL used for ASB definition.
• Culture results take 24h; susceptibilities an additional 24-48h.
• Contamination with distal urethral/vaginal/skin flora is common.
• In catheterized patients: pyuria + bacteriuria alone without symptoms does NOT diagnose UTI.

Imaging (in pyelonephritis/complicated cases):

• CT scan or ultrasound recommended in men with febrile UTI (even first episode) to evaluate for abnormalities/obstruction.
• Emphysematous pyelonephritis - severe form with gas in renal/perinephric tissue; almost exclusively in poorly controlled diabetes.
• Xanthogranulomatous pyelonephritis - chronic urinary obstruction (often by staghorn calculi) with chronic infection leading to suppurative destruction of renal tissue.
• Harrison's Principles 22E, p. 1133-1135

In Recurrent UTI:

• Renal tract ultrasound to exclude anatomical pathology.
• Cystoscopy reserved for atypical symptoms, haematuria, suspected underlying pathology (bladder cancer, stones, fistula).

8. TREATMENT

8a. Uncomplicated Cystitis in Women (Harrison's 22E, p. 1131)

• Fluoroquinolones - highly effective but FDA advises AGAINST use for uncomplicated cystitis in women unless no alternatives (collateral damage, tendon rupture, aortic aneurysm risk).
• Beta-lactams - require longer duration (5-7 days); higher clinical failure rates vs TMP-SMX/fluoroquinolones.
• Important: Fluoroquinolones and TMP-SMX preferred over beta-lactams for men with suspected prostate involvement (superior prostate penetration).

8b. Uncomplicated Cystitis in Men

• True uncomplicated cystitis in afebrile men: 7 days of antimicrobial therapy.
• Durations <7 days used in women have NOT been adequately studied in men.

8c. Pyelonephritis Treatment (Harrison's 22E + Goldman-Cecil)

• Oral fluoroquinolone x 7 days (ciprofloxacin or levofloxacin) - preferred if local resistance <10%.
• Oral TMP-SMX x 14 days if susceptibility known.

• IV cephalosporin (e.g., ceftriaxone 1g IV daily)
• IV fluoroquinolone
• IV aminoglycoside
• Duration: 7-10 days (up to 14 days for severe).

• Remove catheters, stents, stones if possible.
• Ciprofloxacin 400 mg IV q8-12h OR levofloxacin 750 mg IV once daily.
• Aminoglycosides: amikacin 15 mg/kg/24h.
• Antipseudomonal beta-lactam/BLIs: piperacillin-tazobactam 4.5g q8h.
• Carbapenems: doripenem 500 mg IV q8h (infused over 1h) x10 days.
• For difficult-to-treat Pseudomonas: ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, cefiderocol (first-line).

• Drain if ≥3 cm.
• Prolonged antibiotics: 4-6 weeks.

8d. UTI in Pregnancy (Rosen's EM, p. 303-307; Tintinalli, p. 667-668)

• Screen with urine culture at 12-16 weeks or first prenatal visit (USPSTF Grade A).
• Treat for 7-10 days (safe antibiotics): cephalexin 500 mg BD-QID x 3-7 days, amoxicillin 500 mg TID x 7 days, nitrofurantoin 100 mg BD x 3-7 days (avoid in 1st trimester - possible birth defects).
• TMP-SMX: avoid in 3rd trimester (kernicterus risk); trimethoprim (folate antagonist) usable after 1st trimester.
• Avoid: fluoroquinolones (fetal malformations in animals), tetracyclines (impair bone/tooth calcification), sulfonamides in 3rd trimester.

• Usually requires hospital admission for IV antibiotics.
• IV ceftriaxone 1g daily (preferred; ampicillin resistance to E. coli is considerable).
• IV hydration + obstetric consultation + urine cultures.
• Carries risk of maternal sepsis, permanent renal injury, premature labour.
• Premature labour can be prevented by aggressive early treatment.

8e. Spinal Cord Injury UTI Management (Campbell-Walsh-Wein, p. 795-811)

• Treat bacteriuria ONLY if symptomatic (National Institute on Disability and Rehabilitation Research Group).
• Use antibiotics with minimal impact on normal flora.
• Duration: at least 5 days; 7-14 days for reinfection/relapse.
• Repair structural and functional risk factors.
• Prophylaxis only in recurrent UTI when no underlying cause found, especially with dilated upper tracts.
• Do NOT use antibiotics to prevent UTI in patients with indwelling catheter or intermittent catheterization.
• Hydrophilic catheters preferred (evidence supporting lower infection risk).

9. PREVENTION OF RECURRENT UTI

Non-antibiotic approaches:

• D-mannose: Blocks bacterial FimH adhesion to urothelium.
• Cranberry products: Mechanism involves proanthocyanidins inhibiting fimbriae-mediated adherence.
• Vaginal lactobacilli restoration / Probiotics: Reinstate normal vaginal flora; evidence from recent RCT (Gupta et al., Clin Infect Dis 78:1154, 2024).
• Topical vaginal oestrogen: Demonstrated to reduce recurrent UTI frequency in postmenopausal women without altering systemic hormone levels.
• Glucosaminoglycan layer restoration (e.g., hyaluronic acid instillation): Under investigation.
• Vaccination (FimH or iron receptors): Under investigation.
• Immune stimulation (OM-89): Recent trial showed no benefit.
• Vitamin D: Proposed to enhance antimicrobial peptide production; under investigation.

Antibiotic prophylaxis:

• Post-coital prophylaxis for women with sex-related recurrent UTI.
• Continuous low-dose prophylaxis (e.g., nitrofurantoin, TMP-SMX, fosfomycin) in highly selected patients.
• Brenner & Rector's The Kidney, p. 4477-4478
• Harrison's Principles 22E, p. 1133

10. SPECIAL CLINICAL SCENARIOS

Emphysematous Pyelonephritis

• Gas in renal and perinephric tissues.
• Occurs almost exclusively in poorly controlled diabetes.
• Severe, life-threatening; requires aggressive management including drainage.

Xanthogranulomatous Pyelonephritis

• Chronic urinary obstruction (often staghorn calculi) + chronic infection.
• Leads to suppurative destruction of renal tissue.
• Treatment: surgical (nephrectomy often required).

Papillary Necrosis

• Obstructive uropathy from sloughed papillae obstructing the ureter can complicate pyelonephritis.
• Also occurs in sickle cell disease and analgesic nephropathy.
• Bilateral papillary necrosis: rapid rise in serum creatinine may be first sign.

Renal Scarring from Pyelonephritis

• Renal scars detected in 29-46% of women requiring hospitalization for pyelonephritis.
• However, scars not associated with hypertension or renal impairment in follow-up.
• Brenner & Rector's The Kidney, p. 4488-4489

UTI in Paediatrics / Prenatal Hydronephrosis (Campbell-Walsh-Wein, p. 1179)

• UTI in 8-22% of patients with prenatal urinary tract dilation (UTD).
• Grade of hydronephrosis is predictive of UTI risk: 4%, 14%, 33%, 40% for grades 1-4 respectively (Lee et al. meta-analysis).
• Risk factors: female gender, high-grade dilation, intact foreskin, ureteral dilation, VUR.

CAUTI (Catheter-Associated UTI)

• Catheterized patients almost always have pyuria AND bacteriuria - do NOT diagnose UTI without symptoms.
• Strategies to prevent CAUTI (2022 update: Infect Control Hosp Epidemiol 44:1209, 2023): limit catheter use, sterile insertion, closed drainage systems, early removal.

11. STERILE PYURIA (Differential Diagnosis)

• Fastidious organisms (TB, gonorrhea)
• Carcinoma in situ of the bladder
• Bladder stones
• Other inflammatory conditions
• Chlamydial urethral infection (differential for dysuria with negative culture)
• Herpes genitalis, vaginitis (external dysuria)
• Bailey & Love 28E, p. 1532

12. PROSTATITIS - CLASSIFICATION (Harrison's 22E)

KEY CLINICAL PEARLS

1. ASB vs UTI - ASB should NOT be treated except in pregnancy or pre-urologic procedure.
2. Nitrofurantoin - cannot treat pyelonephritis (insufficient tissue levels); contraindicated if CrCl <30 mL/min.
3. Fluoroquinolones - FDA advises against for uncomplicated cystitis in women; preferred for male UTI with prostate involvement.
4. Negative dipstick (both nitrite AND leukocyte esterase) - should prompt alternative diagnoses; BUT does NOT rule out bacteriuria in pregnancy.
5. Pyelonephritis in pregnancy - early aggressive treatment prevents premature labour.
6. Treat bacteriuria only if symptomatic in SCI/catheterized patients.
7. Right-sided predominance in pregnancy - physiologic right ureteral dilation > left; 75% vs 33% hydronephrosis after mid-pregnancy.
8. Biofilm formation (IBCs/QIRs) - explains why recurrent UTI is difficult to eradicate with standard antibiotic courses.
9. Fosfomycin / Pivmecillinam - preferred alternatives for MDR E. coli cystitis including ESBL-producers.
10. Male febrile UTI - always image (CT/US) even at first episode to exclude obstruction/structural abnormality.