What is the recommended treatment for an abnormal urinary tract infection (UTI) caused by lactose fermenting Gram-negative bacilli, such as Escherichia coli (E. coli)?

Treatment of UTI Caused by Lactose-Fermenting Gram-Negative Bacilli

For uncomplicated UTIs caused by lactose-fermenting gram-negative bacilli (primarily E. coli), use nitrofurantoin 100mg twice daily for 5 days or fosfomycin 3g single dose as first-line therapy. 1, 2

Severity-Based Treatment Algorithm

Uncomplicated Lower UTI (Cystitis)

• First-line options:

  • Nitrofurantoin 100mg PO twice daily for 5 days 1, 2
  • Fosfomycin 3g PO single dose 1, 2
  • Trimethoprim-sulfamethoxazole (if local resistance <20% and no recent use in past 3-6 months) 3, 4

• Second-line options (if first-line unavailable or contraindicated):

  • Amoxicillin-clavulanate 1, 2
  • Cephalexin or other oral cephalosporins 2
  • Fluoroquinolones (ciprofloxacin) only if local resistance is low and other options unsuitable 1, 5

Complicated UTI or Pyelonephritis (Non-Severe)

For non-severe complicated UTI without septic shock, choose based on resistance pattern:

• If third-generation cephalosporin-susceptible:

  • Piperacillin-tazobactam 6
  • Amoxicillin-clavulanate 6
  • Fluoroquinolones (ciprofloxacin) if susceptible 6
  • Cotrimoxazole for non-severe cases 6

• If third-generation cephalosporin-resistant (3GCephRE) without septic shock:

  • Aminoglycosides (when active in vitro) for short duration (≤7 days to minimize nephrotoxicity) 6
  • IV fosfomycin (strong recommendation, high-quality evidence from ZEUS and FOREST trials) 6
  • Caution: Monitor for heart failure with IV fosfomycin (8.6% incidence in FOREST trial) 6

Severe Infections or Bloodstream Infection

For severe UTI with septic shock or bloodstream infection due to 3GCephRE, use carbapenem (imipenem or meropenem) as targeted therapy. 6

• Without septic shock: Ertapenem may be used instead of imipenem/meropenem 6
• Treatment duration: 7-14 days for pyelonephritis or complicated UTI 3, 1

Carbapenem-Resistant Organisms (CRE)

If carbapenem resistance is documented:

• Severe infections: Meropenem-vaborbactam or ceftazidime-avibactam (if active in vitro) 6
• Non-severe UTI: Aminoglycosides including plazomicin, chosen based on individual susceptibility 6
• Metallo-β-lactamase producers: Cefiderocol 6

Critical Pitfalls to Avoid

• Do NOT use fluoroquinolones as first-line for uncomplicated UTI due to increasing resistance rates and adverse effect profile 1, 2
• Do NOT use trimethoprim-sulfamethoxazole empirically if local resistance >20% or recent exposure within 3-6 months 1, 2
• Do NOT use tigecycline for 3GCephRE infections (strong recommendation against) 6
• Do NOT use cephamycins or cefepime for 3GCephRE infections 6
• Avoid aminoglycosides beyond 7 days due to nephrotoxicity risk 6
• Reserve new β-lactam/β-lactamase inhibitors (ceftazidime-avibactam, meropenem-vaborbactam) for extensively resistant bacteria per antibiotic stewardship 6

De-escalation Strategy

Once patient stabilizes and susceptibilities are available, step down from carbapenems to:

• Older β-lactam/β-lactamase inhibitors 6
• Quinolones (if susceptible) 6
• Cotrimoxazole (if susceptible) 6
• Oral agents based on susceptibility pattern 6

This de-escalation approach is considered good clinical practice for antibiotic stewardship 6

Special Populations

• Pregnancy: Avoid fluoroquinolones and trimethoprim-sulfamethoxazole in first trimester; nitrofurantoin and β-lactams are preferred 5
• Pediatrics: Ciprofloxacin is indicated for complicated UTI/pyelonephritis in children but not first-choice due to increased joint-related adverse events (9.3% vs 6% in controls) 5
• Elderly: Increased risk of tendon rupture with fluoroquinolones, especially with concurrent corticosteroids 5