UrinaryTract Infections: Cystitis, Prostatitis, and Pyelonephritis¶
Part 5: Infectious Diseases | Chapter 140 – Bacterial Infections of the Urinary Tract · Part 5 – Infectious Diseases: Bacterial · Chapter 140
Key Clinical Points¶
- UTI is defined as a symptomatic infection; asymptomatic bacteriuria (ASB) requires no treatment except in pregnancy or pre-procedural urology.
- E. coli is the primary pathogen (75–90% of cystitis, 80% of pyelonephritis), with >20% resistance to TMP-SMX, fluoroquinolones, and nitrofurantoin in many regions.
- CAUTI requires symptoms + bacteriuria (≥10^5 CFU/mL) and pyuria (>10 leukocytes/HPF); catheter-associated bacteriuria alone is not an infection.
- Pyuria is defined as >10 leukocytes/HPF; dipstick-negative nitrite/leukocyte esterase should prompt non-UTI evaluation.
- Febrile UTI in men requires imaging (CT/ultrasound) to evaluate for obstruction or prostatitis.
- Emphysematous pyelonephritis occurs almost exclusively in poorly controlled diabetes with gas production in renal tissue.
- Xanthogranulomatous pyelonephritis results from chronic obstruction + infection, mimicking renal malignancy on imaging.
- ASB screening/treatment in pregnancy prevents pyelonephritis, preterm delivery, and low birth weight.
- SGLT-2 inhibitors increase UTI risk via glycosuria; an FDA drug-safety warning exists for this association.
- In elderly patients with altered mental status, UTI must be distinguished from delirium; empirical therapy should not be withheld without ruling out sepsis.
1. DEFINITION & OVERVIEW¶
Urinary tract infection (UTI) refers to symptomatic infection along the urinary tract, distinct from asymptomatic bacteriuria (ASB). UTI encompasses cystitis (bladder), prostatitis (prostate), and pyelonephritis (kidneys).
Key Distinctions:
• UTI: Requires treatment to relieve symptoms and prevent progression. • ASB: Defined as bacterial presence in urine without symptoms; typically does not require treatment. • CAUTI (Catheter-associated UTI): Defined as UTI with catheterization, requiring symptoms + bacteriuria ≥10^5 CFU/mL and pyuria (>10 leukocytes/HPF).
1.1 Exceptions to ASB Non-treatment¶
Two specific scenarios require treatment of ASB:
- Pregnancy: Untreated ASB increases risk of pyelonephritis, preterm delivery, and low birth weight.
- Pre-procedural urology: Required before procedures (e.g., lithotripsy) due to the risk of bacterial translocation.
1.2 Classification Systems¶
New classification systems prioritize clinical context over traditional risk-based categorization:
• Uncomplicated UTI: Bladder infection in non-catheterized individuals. • Complicated UTI: Infection extending beyond the bladder (e.g., prostatitis, pyelonephritis, bacteremia) or in catheterized patients (CAUTI).
Management Considerations: 1. Patient stability for outpatient care. 2. Identification of recurring infection sources (e.g., obstructing calculi). 3. Antimicrobial penetration into blood/renal tissue.
2. EPIDEMIOLOGY¶
Incidence patterns:
• Neonatal period: Slightly higher in males due to congenital anomalies. • Post-50 years: UTI rates in men approach those of women due to prostatic hypertrophy. • 1–50 years: Predominantly female, with most male UTIs occurring in catheterized patients or those with anatomic abnormalities.
Prevalence:
• 20–40-year-old women: ~5% ASB; 80% experience at least one UTI (mostly acute cystitis). • Elderly individuals: Up to 40–50% ASB. • Men: Lifetime prevalence of ~14%.
2.1 Risk Factors¶
Key risk factors include:
• Behavioral/sexual: Frequent intercourse, spermicide use, new sexual partners. • Anatomic: Congenital anomalies, pelvic organ prolapse, benign prostatic hypertrophy. • Medical: Diabetes (2–3× higher ASB/UTI risk), SGLT-2 inhibitors (glycosuria increases UTI risk). • Environmental: Urinary instrumentation (catheterization, stents), foreign bodies (stones). • Hormonal: Menopause (vaginal lactobacilli loss), postmenopausal estrogen therapy. • Genetic: Familial history of UTI; specific E. coli colonization patterns.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Etiology:
• Predominant pathogen: Escherichia coli (75–90% of cystitis, 80% of pyelonephritis). • Other pathogens: Staphylococcus saprophyticus, Enterobacterales, Pseudomonas aeruginosa, and Candida in CAUTI.
Resistance trends:
• General resistance: >20% resistance to TMP-SMX, fluoroquinolones, and nitrofurantoin in many regions. • Multidrug resistance: 6–9% are multidrug-resistant (ESBL producers).
Pathogenesis mechanisms:
- Ascending infection: Bacteria ascend from urethra → bladder → kidneys.
- Hematogenous spread (<2% of UTIs): S. aureus, Salmonella.
- Foreign bodies: Catheters, stones provide bacterial colonization sites.
- Host factors: Genetic predisposition (e.g., Toll-like receptor mutations), mucosal defenses (lactobacilli in vagina).
3.1 Pathogenesis Details¶
Key mechanisms:
• Bacterial adhesion: To uroepithelial cells via P fimbriae (pyelonephritis) and type 1 pili. • Biofilm formation: On foreign bodies (catheters, stones). • Intracellular communities: In bladder epithelium (animal models only).
3.2 Virulence Factors¶
- E. coli virulence: P fimbriae (renal adhesion), type 1 pili (colonization), toxins, and iron acquisition systems.
- Candida: Hematogenous spread common in catheterized patients.
3.3 Host & Environmental Factors¶
• Genetic: Familial UTI risk, Toll-like receptor mutations. • Mucosal: Vaginal lactobacilli loss (menopause), urothelial adhesion differences in recurrent UTI patients. • Environmental: E. coli colonization from intestinal flora; spermicide toxicity to lactobacilli. • Postmenopausal changes: Vaginal atrophy → Gram-negative overgrowth; topical estrogen reduces recurrent UTI risk.
4. CLINICAL FEATURES¶
Symptoms:
• Cystitis: Dysuria, urgency, frequency, suprapubic pain, nocturia. • Prostatitis: Dysuria, pelvic/perineal pain, urinary retention; systemic signs in acute bacterial prostatitis (ABP). • Pyelonephritis: Fever (key differentiator), flank pain, nausea/vomiting, rigors. • CAUTI: Systemic symptoms (fever) or localized urinary symptoms despite expected bacteriuria/pyuria.
4.1 Cystitis¶
- Diagnosis: History alone in women; urine dipstick/microscopy/culture if uncertain.
- Red flags: Fever, flank pain → pyelonephritis/prostatitis evaluation.
4.2 Prostatitis¶
- Acute bacterial prostatitis (ABP): Severe dysuria, pelvic/perineal pain, fever, urinary retention.
- Chronic bacterial prostatitis (CBP): Recurrent cystitis with pelvic pain; no systemic signs.
- Evaluation: Urine culture in recurrent cases; imaging for obstruction.
4.3 Pyelonephritis¶
- Mild: Low-grade fever, costovertebral angle tenderness.
- Severe: High fever, rigors, nausea/vomiting, flank pain.
- Complications: Acute papillary necrosis (sickle cell disease, analgesic nephropathy), emphysematous pyelonephritis (diabetes), xanthogranulomatous pyelonephritis (chronic obstruction).
4.4 CAUTI¶
- Diagnosis: Symptoms + bacteriuria ≥ 10^5 CFU/mL and pyuria.
- Challenges: Bacteriuria/pyuria are expected in catheterized patients; systemic symptoms (fever) or localized urinary symptoms required for diagnosis.
5. DIFFERENTIAL DIAGNOSIS¶
Key differentials:
• ASB vs UTI: ASB has no symptoms; UTI requires treatment. • Male UTI vs chronic pelvic pain syndrome (CPPS): CPPS lacks bacteriuria and does not respond to antibiotics. • STI mimics: Gonococcal urethritis, chlamydial infection (dysuria, discharge).
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic criteria:
• Urinalysis: Pyuria (>10 leukocytes/HPF), nitrite/leukocyte esterase. • Culture thresholds: Bacteriuria ≥ 10^5 CFU/mL for UTI; <10^4 CFU/mL in catheterized patients (ASB). • Imaging indications: Febrile UTI in men → CT/ultrasound to evaluate obstruction/prostatitis.
6.1 Urinalysis & Microscopy¶
- Pyuria: >10 leukocytes/HPF.
- Nitrite/leukocyte esterase: Suggests UTI; negative results prompt non-UTI evaluation.
6.2 Culture Thresholds¶
- UTI: ≥ 10^5 CFU/mL.
- ASB: <10^4 CFU/mL (except in pregnancy/procedural settings).
6.3 Imaging Indications¶
- Febrile UTI in men: CT/ultrasound to evaluate obstruction, prostatitis.
- Recurrent UTI: Urologic consultation for anatomical abnormalities.
7. MANAGEMENT & TREATMENT¶
Empiric therapy principles:
• Uncomplicated cystitis: TMP-SMX, nitrofurantoin, fosfomycin. • Complicated UTI/CAUTI: Ciprofloxacin, levofloxacin, piperacillin-tazobactam. • ASB: No treatment except in pregnancy/procedural settings (e.g., ceftriaxone).
Special considerations:
• Pregnancy: Nitrofurantoin (avoid 36–40 weeks), cephalexin. • SGLT-2 inhibitors: Monitor for UTI risk; consider alternative glucose control if recurrent. • Elderly patients: Avoid catheterization if possible; treat ASB in delirium with suspicion of UTI.
7.1 Empiric Therapy Principles¶
- Uncomplicated cystitis (women): TMP-SMX, nitrofurantoin, fosfomycin.
- Complicated UTI/CAUTI: Ciprofloxacin, levofloxacin, piperacillin-tazobactam.
- ASB: No treatment except in pregnancy/procedural settings (e.g., ceftriaxone).
7.2 CAUTI Management¶
- Antibiotics: Ciprofloxacin, levofloxacin, piperacillin-tazobactam.
- Catheter removal: If possible; persistent infection may require catheter change.
7.3 ASB Management¶
- Pregnancy: Cephalexin, nitrofurantoin (avoid 36–40 weeks).
- Pre-procedural urology: Ceftriaxone or ciprofloxacin.
8. PROGNOSIS & COMPLICATIONS¶
Recurrence:
• Frequency: 20–30% of women with first UTI experience recurrence. • Timing: Early recurrence (<2 weeks) may indicate relapse vs. reinfection. • Annual rate: 0.3–7.6 infections/patient/year (avg 2.6).
Severe complications:
• Emphysematous pyelonephritis: Gas in renal tissue; almost exclusively in diabetes. • Xanthogranulomatous pyelonephritis: Chronic obstruction + infection → suppurative destruction of tissue; mimics malignancy. • Intraparenchymal abscesses: Persistent fever/bacteremia despite antibiotics. • Acute papillary necrosis: Obstruction from sloughed papillae (seen in sickle cell disease or analgesic nephropathy).
8.1 Recurrence Details¶
- Early recurrence (<2 weeks): Relapse vs. reinfection.
- Annual rate: 0.3–7.6 infections/patient/year (avg 2.6).
8.2 Severe Complications¶
- Emphysematous pyelonephritis: Gas in renal parenchyma; diabetes is a risk factor.
- Xanthogranulomatous pyelonephritis: Chronic obstruction + infection → granulomatous inflammation.
- Acute papillary necrosis: Obstruction from sloughed papillae; sickle cell disease/analgesic nephropathy.
9. SPECIAL CONSIDERATIONS¶
Key scenarios:
• Pregnancy: ASB screening at 12–16 weeks; treatment to prevent pyelonephritis, preterm delivery, and low birth weight. • Diabetes/SGLT-2 Inhibitors: Glycosuria increases UTI risk; FDA warning issued. Monitor for UTI; consider alternative glucose control if recurrent. • Catheterized patients: CAUTI management; avoid unnecessary catheterization; use aseptic techniques. • Elderly/immunocompromised: Delirium often caused by UTI; treat empirically if sepsis is ruled out. Higher risk of fungal infections (e.g., candiduria) in immunocompromised.
9.1 Pregnancy¶
- Screening: ASB at 12–16 weeks.
- Treatment: Cephalexin, nitrofurantoin (avoid 36–40 weeks).
9.2 Diabetes & SGLT-2 Inhibitors¶
- SGLT-2 inhibitors: Glycosuria increases UTI risk; FDA warning issued.
- Diabetes management: Monitor for UTI; consider alternative glucose control if recurrent.
9.3 Catheterized Patients¶
- CAUTI prevention: Avoid unnecessary catheterization; use aseptic techniques.
- Management: Ciprofloxacin, levofloxacin, piperacillin-tazobactam.
9.4 Elderly & Immunocompromised¶
- Delirium evaluation: UTI is a common cause; treat empirically if sepsis is ruled out.
- Immunocompromised: Higher risk of fungal infections (e.g., candiduria).
10. KEY PEARLS & CLINICAL TRAPS¶
• Pearl 1: ASB in pregnant women requires treatment to prevent pyelonephritis.
• Pearl 2: Emphysematous pyelonephritis is a medical emergency in diabetic patients.
• Trap 1: Bacteriuria alone in catheterized patients does not indicate infection (CAUTI requires symptoms + pyuria).
• Trap 2: Dipstick-negative nitrite/leukocyte esterase should prompt non-UTI evaluation.
11. WHAT TO LOOK FOR — DIAGNOSTIC CLUES¶
• Pyelonephritis: Fever, flank pain, costovertebral angle tenderness. • Emphysematous pyelonephritis: Gas on imaging in diabetic patients. • Xanthogranulomatous pyelonephritis: Chronic obstruction + infection → granulomatous inflammation on biopsy.
12. WHAT EXCLUDES THE DIAGNOSIS¶
• ASB: No symptoms. • Non-UTI mimics: STIs (e.g., gonococcal urethritis), interstitial cystitis, bladder cancer. • Catheter-associated bacteriuria without symptoms: Not CAUTI.
13. DIAGNOSTIC FLOWCHART¶
The following decision tree outlines the diagnostic pathways based on clinical presentation:
Pathway A (Uncomplicated Cystitis): Acute onset of urinary symptoms → Otherwise healthy woman not in poor risk for multidrug resistance → Consider uncomplicated cystitis.
Pathway B (STI Risk): Acute onset of urinary symptoms → Woman with history of risk factors for STI → Consider uncomplicated cystitis or STI.
Pathway C (Prostatitis): Acute onset of urinary symptoms → Male with urethral, pelvic, or prostate pain → Consider acute prostatitis.
Pathway D (CAUTI): Acute onset of urinary symptoms → Patient with indwelling urinary catheter → Consider CAUTI.
Pathway E (Complicated UTI): Acute onset of urinary symptoms → All other patients → Consider complicated UTI.
Pathway F (Pyelonephritis): Acute onset of back pain + UTI symptoms → Otherwise healthy woman not in poor risk → Consider pyelonephritis.
Pathway G (Pyelonephritis/Prostatitis): Acute onset of back pain + UTI symptoms → All other patients → Consider pyelonephritis or acute prostatitis (male).
Pathway H (Systemic Symptoms): Systemic symptoms (Fever, altered mental status) → All other patients → Consider complicated UTI.
Pathway I (Procedure-related): No urinary symptoms → Positive urine culture in patient undergoing invasive urologic procedure → Consider ASB.
Pathway J (General Asymptomatic/Other): No urinary symptoms → Positive urine culture in all other patients → Consider CAUTI.
Pathway K (Catheter-related asymptomatic): No urinary symptoms → Positive urine culture in patient with indwelling catheter → Consider CA-ASB.
Pathway L (Recurrent Cystitis): Recurrent acute urinary symptoms → Otherwise healthy woman not in poor risk → Consider recurrent cystitis.
Pathway M (Male Recurrence): Recurrent acute urinary symptoms → Male patient → Consider complicated UTI.
14. TREATMENT TABLE¶
Table 140-1: Treatment Strategies for Acute Uncomplicated Cystitis
| Drug | Dose | Duration | Common Side Effects |
|---|---|---|---|
| Nitrofurantoin | 100 mg bid (5–7 days) OR 1 DS tablet bid (3 days for women; 7 days for men) | Nausea, headache | |
| Fosfomycin | 3-g sachet (1 day) OR 400 mg bid (3–7 days) | Diarrhea, nausea, headache | |
| Fluoroquinolones | Dose varies by agent; Duration: 3 days (women) or 7 days (men); or 5–7 days for both. | Nausea, vomiting, diarrhea, headache, drowsiness, insomnia | |
| β-Lactams | Dose varies by agent; Duration: 5–7 days for both. | Varies |
Reference Tables¶
TABLE 140-1 Treatment Strategies for Acute Uncomplicated Cystitis DRUG Nitrofurantoin TMP-SMX Fosfomycin Pivmecillinam…¶
Harrison's 22e, p.1093
| DRUG | DOSE | DURATION | COMMON SIDE EFFECTS |
|---|---|---|---|
| Nitrofurantoin | 100 mg bid | Women or men: 5–7 days | Nausea, headache |
| 1 DS tablet bid | Women: 3 days Men: 7 days | ||
| Fosfomycin | 3-g sachet | Women: 1 day Men: qod × 3 doses |
Diarrhea, nausea, headache |
| 400 mg bid | Women: 3–7 days | ||
| Fluoroquinolones | Dose varies by agent | Women: 3 days Men: 7 days |
Nausea, vomiting, diarrhea, headache, drowsiness, insomnia |
| Dose varies by agent | Women or men: 5–7 days |