Urinary tract infection

Background

• Bacterial infection of the urinary tract, either lower (cystitis) or upper (pyelonephritis)
• When UTI causes sepsis syndrome, often referred to as urosepsis

Microbiology

• Gram-negative bacteria
  • Escherichia coli, most common cause overall
  • Proteus, Klebsiella, Enterobacter
  • Pseudomonas, Acinetobacter
• Gram-positive bacteria
  • Staphylococcus saprophyticus, more common in young women
  • Enterococcus faecalis
  • Staphylococcus aureus, as a complication of Staphylococcus aureus bacteremia
  • Corynebacterium urealyticum
• Viruses
  • Adenovirus, which can cause hemorrhagic cystitis in hematopoietic stem cell transplantation recipients
  • BK virus, in renal transplant recipients

Risk Factors

• Premenopausal women: sexual intercourse, new partner, no postcoital voiding, spermicide use, prior UTI, diabetes mellitus
• Postmenopausal women: genitourinary atrophy/estrogen deficiency, urethral diverticulum, vaginal prolapse beyond the hymen, incontinence, postvoid residual, catheterization
• Men: reduced prostatic secretions (older men), postvoid residual, incontinence, catheterization

Clinical Manifestations

• Acute simple cystitis: acute UTI without signs of upper tract infection or systemic symptoms
• Acute complicate UTI: acute UTI with fever, chills, malaise, flank pain, CVA tenderness, or (in men) pelvic/perineal pain
• Diagnostic criteria include clinical and laboratory symptoms:
  • Two or more clinical symptoms:
    • Fever > 38ºC
    • Urinary urgency or frequency
    • Acute dysuria
    • Hypogastric pain
    • Costovertebral angle tenderness
  • One or more laboratory finding:
    • Bacteriuria (> 100,000 CFUs/mL)
    • Pyuria (>10 WBCs/HPF)

Investigations

• Urinalysis
  • Leukocyte esterase
  • Nitrite, positive for organisms that convert nitrate to nitrite such as the Gram-negative bacteria
  • High negative predictive value if both LE and nitrite are negative
• Urine microscopy
  • Pyuria indicated by 5-10 cells per HPF

Management

• Acute afebrile UTI in men: 7 days ciprofloxacin or cotrimoxazole1
• Acute afebrile UTI in women:
  • First-line antibiotics
    • Nitrofurantoin monohydrate/macrocrystals (Macrobid) 100 mg p.o. twice daily for 5 days
    • Co-trimoxazole DS p.o. twice daily for 3 days
    • Fosfomycin 3 g p.o. once
    • Trimethoprim 100 mg p.o. twice daily for 3 days
    • Pivmecillinam 400 mg p.o. three times daily for 3 to 5 days
  • Second-line is a β-lactam
    • Amoxicillin-clavulanic acid 500 mg/125 mg p.o. twice daily for 5 to 7 days
    • Cefadroxil 500 mg p.o. twice daily for 5 to 7 days
    • Cephalexin 250 to 500 mg p.o. every 6 hours for 5 to 7 days
  • Last-line is a fluoroquinolone
    • Ciprofloxacin 250 mg p.o. twice daily for 3 days
    • Ciprofloxacin XR 500 mg p.o. daily for 3 days
    • Levofloxacin 250 mg p.o. daily for 3 days

ESBLs

• Uncomplicated UTIs:
  • Preferred: nitrofurantoin or co-trimoxazole
  • Alternatives: amoxicillin-clavulanate (if in vitro susceptibility), single-dose aminoglycosides, and oral fosfomycin (for E. coli)
• Complicated UTIs and pyelonephritis:
  • Preferred: ertapenem, meropenem, imipenem-cilastatin, ciprofloxacin, levofloxacin, or trimethoprim-sulfamethoxazole
  • Alternatives: once-daily aminoglycosides

CREs

• Uncomplicated UTIs:
  • Preferred: ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, or a single-dose of an aminoglycoside
  • Alternative: meropenem (if susceptible), ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol
  • Also: single-dose aminoglycosides
  • For CRE E. coli: fosfomycin
  • If necessary: colistin
• Complicated UTIs and pyelonephritis:
  • Preferred: ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole
  • Alternative: extended-infusion meropenem (if susceptible), ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol
  • Also: once-daily aminoglycosides