Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis

Harrison's Principles of Internal Medicine, 22nd Edition (2025)

Historical Context

Definitions

Key distinction: UTI requires symptoms. Bacteria alone (even with pyuria) in an asymptomatic patient = ASB, NOT UTI. This has major clinical implications.

1. Pregnant patients (untreated ASB → pyelonephritis, preterm delivery, low birth weight)
2. Patients about to undergo urologic procedures with mucosal injury (lithotripsy, TURP)

Epidemiology and Risk Factors

• UTI is extremely common, one of the leading reasons for antibiotic use in all healthcare settings.
• Far more prevalent in women than men; most research has focused on healthy young women.

• Anatomical: Congenital urinary tract abnormalities, cystoceles, pelvic organ prolapse, urinary obstruction or retention, urolithiasis
• Behavioral: Sexual activity (especially new/multiple partners), spermicide use
• Hormonal/physiologic: Postmenopausal status (reduced estrogen → mucosal changes)
• Urinary catheters: Indwelling or intermittent catheterization
• Functional/structural: Urinary retention, neurogenic bladder, diabetes mellitus, immunosuppression

Microbiology / Causative Organisms

• Uropathogenic Escherichia coli (UPEC) is the most common causative organism, responsible for ~80% of uncomplicated cystitis.
• Other common pathogens: Staphylococcus saprophyticus (especially in young sexually active women), Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis
• Complicated UTIs may involve a broader spectrum including Pseudomonas aeruginosa, Enterobacter, and resistant organisms (ESBL-producers, carbapenem-resistant organisms)
• Mixed cultures usually represent contamination (except in long-term catheterization, chronic urinary retention, or urinary-GI/genital fistulae)

Pathogenesis

1. Uropathogens colonize the periurethral area (especially in women, whose short urethra facilitates ascent).
2. Bacteria ascend into the bladder.
3. In pyelonephritis, bacteria ascend further via ureters to the renal pelvis and parenchyma.
4. UPEC expresses multiple virulence factors: type 1 fimbriae (bladder adhesion), P fimbriae (upper tract invasion), flagella (motility/ascent), iron acquisition systems, toxins (e.g., hemolysin).

Asymptomatic Bacteriuria (ASB)

• Both UTI and ASB feature bacteria in the urine, usually accompanied by pyuria.
• ASB = bacteria without symptoms; usually does NOT require treatment.
• Treating ASB without symptoms → no benefit, potential harm (promotes resistance, disrupts normal flora).
• Screen and treat ASB in: pregnant women, and pre-urologic procedure patients.

Clinical Manifestations

Cystitis

Pyelonephritis

• Emphysematous pyelonephritis: Gas-forming infection of the renal parenchyma; predominantly in diabetics; high mortality; often requires urgent nephrectomy or percutaneous drainage.
• Renal abscess: Focal suppurative infection; may require drainage.
• Xanthogranulomatous pyelonephritis: Chronic destructive infection, often with Proteus or E. coli, associated with staghorn calculi.

Prostatitis

• Acute bacterial prostatitis: Sudden fever, chills, dysuria, pelvic/perineal pain, tender/boggy prostate on DRE. Can progress to prostatic abscess.
• Chronic bacterial prostatitis: Recurrent UTI with same organism; more subtle symptoms; important reservoir for recurrent UTI in men.

Diagnosis

Urinalysis

• Pyuria (>10 WBCs/HPF by traditional cutoff): Present in nearly all cases of cystitis. Note - modern data suggest this cutoff has poor specificity (~36%) particularly in older women. A cutoff closer to 250 WBCs/HPF may better correlate with symptoms.
• Nitrite test: Positive when nitrate-reducing bacteria (Enterobacteriaceae) are present.
• Leukocyte esterase: Proxy for pyuria; moderate sensitivity/specificity.
• Hematuria: Present in ~30% of cystitis cases.

Urine Culture

• Colony count >10² bacteria/mL is more sensitive (95%) than the traditional 10⁵/mL threshold for diagnosis of acute cystitis in women.
• Cultures take 24h for growth; susceptibilities another 24-48h.
• A positive culture alone (without symptoms) = ASB, not UTI.
• Mixed bacterial species typically = contamination.

When to Culture

• Not needed for routine uncomplicated cystitis in otherwise healthy women (treat empirically).
• Indicated for: men with UTI, pregnant women, complicated UTI, pyelonephritis, recurrent UTI, treatment failure, hospitalized patients, unusual/atypical presentations.

Imaging

• Not needed for uncomplicated cystitis.
• Renal ultrasound or CT: Indicated for pyelonephritis with treatment failure, suspected renal abscess, emphysematous changes, obstruction, or renal calculi.
• CT urogram: Gold standard for structural evaluation.

Treatment

General Principles

• Antibiotic treatment is warranted for any true (symptomatic) UTI.
• NSAID-only treatment: Delays clinical response and predisposes to more invasive infections - not recommended.
• "Delayed prescribing" (fill only if no improvement): Has potential to reduce unnecessary antibiotic use but risks prolonging discomfort and small increased risk of progression to pyelonephritis.
• Antimicrobial stewardship priorities: Avoid treating ASB, avoid ordering urine cultures in patients without UTI symptoms, avoid overly long antibiotic durations.
• Local resistance patterns must guide empirical antibiotic choice. TMP-SMX was first IDSA choice in 1999 but local resistance now limits this as a universal recommendation.

Uncomplicated Cystitis (Women)

Complicated UTI / Pyelonephritis

• Fluoroquinolone (ciprofloxacin 500 mg BID x 7 days, or levofloxacin 750 mg x 5 days) - if local fluoroquinolone resistance <10%.
• TMP-SMX (DS BID x 14 days) if susceptibility confirmed.
• Oral beta-lactams (less effective).

• Parenteral therapy required: IV ceftriaxone, IV fluoroquinolone, IV piperacillin-tazobactam, or carbapenems (ertapenem, meropenem) for MDR organisms.
• Empirically cover for ESBL-producing organisms in patients with prior MDR infection, recent healthcare exposure, travel to high-resistance regions.
• Step-down to oral once clinical improvement and susceptibilities known.
• Duration: 7-14 days depending on severity.

UTI in Men (Cystitis / Prostatitis)

• Cystitis in men is considered complicated (by definition) given the presence of prostate tissue that may harbor infection.
• Fluoroquinolones and TMP-SMX have good prostatic penetration → preferred for suspected prostatitis.
• Acute bacterial prostatitis: IV antibiotics initially if severe (ciprofloxacin or ceftriaxone); step down to oral fluoroquinolone for 4-6 weeks total (or TMP-SMX if susceptible).
• Chronic bacterial prostatitis: Oral fluoroquinolone or TMP-SMX for 4-6 weeks minimum. Difficult to eradicate due to biofilm and poor drug penetration into prostatic tissue.
• Urological evaluation needed for men with recurrent UTI.

UTI in Pregnant Patients

• Drugs of choice: Aminopenicillins (ampicillin, amoxicillin) and cephalosporins (but aminopenicillin resistance is widespread - do not use empirically without culture).
• Nitrofurantoin: Usable all trimesters if beta-lactams unavailable (ACOG 2023 guidance); one retrospective study suggested first-trimester teratogenicity, but not confirmed.
• TMP-SMX (sulfonamides): Avoid first trimester (teratogenicity concern) and near term (neonatal kernicterus); ACOG allows use if no alternatives.
• Fluoroquinolones: Avoid (fetal cartilage development concerns).
• Duration of treatment:
  • ASB/cystitis in pregnancy: 5-7 days (shorter durations lack evidence).
  • Pyelonephritis: Parenteral beta-lactam therapy ± aminoglycosides.

Catheter-Associated UTI (CAUTI)

• CAUTI = UTI occurring in a patient with an indwelling urinary catheter (or within 48h of removal).
• Most important prevention: Remove the catheter as soon as it is no longer needed.
• Definition challenge: Catheterized patients routinely develop ASB; treating ASB in catheterized patients does not reduce UTI rates and promotes resistance.
• Treat CAUTI only if: Patient has symptoms attributable to the urinary tract (fever, suprapubic pain, CVA tenderness, change in mental status in elderly, hemodynamic instability).
• When treating CAUTI: Change or remove the catheter before/during treatment; send urine culture.
• Antibiotic choice: Based on culture results; empirical coverage depends on local resistance patterns and patient risk factors.

Candiduria

• Increasingly common in ICU patients, those on broad-spectrum antibiotics, and diabetics with indwelling catheters.

• 50% of urinary Candida isolates are non-C. albicans species.

• Management:
  • Asymptomatic candiduria: Remove catheter (resolves in >1/3 of cases); do NOT routinely treat.
  • Symptomatic cystitis or pyelonephritis: Treat.
  • Asymptomatic but high-risk (neutropenia, pre-urologic procedure, low-birth-weight infants): Treat.
• First-line: Fluconazole 200-400 mg/day for 7-14 days (achieves high urinary levels).
• Fluconazole-resistant Candida: Oral flucytosine and/or parenteral amphotericin B.
• Bladder irrigation with amphotericin B: Not recommended.
• Newer azoles/echinocandins: Not first-line (relatively unstudied for urinary infections).

Prevention of Recurrent UTI in Women

Special Populations Summary

Key Antimicrobial Stewardship Messages (Harrison's)

1. Do not treat ASB (except in pregnancy and pre-urologic procedures).
2. Do not order urine cultures in patients without UTI symptoms.
3. Use the shortest effective antibiotic course.
4. Fluoroquinolones should be reserved for complicated UTI, not used as first-line for uncomplicated cystitis.
5. Know your local resistance patterns - they drive empirical choice more than any single guideline.
6. NSAID-only treatment is not appropriate.