What antibiotics are recommended for a nitrite-negative urinary tract infection (UTI)?

Antibiotic Selection for Nitrite-Negative Urinary Tract Infections

For nitrite-negative urinary tract infections, fosfomycin 3g single dose is the preferred first-line antibiotic due to its high efficacy against common uropathogens and minimal drug interactions. 1

First-Line Antibiotic Options

The American Urological Association and World Health Organization recommend the following antibiotics for uncomplicated UTIs, regardless of nitrite status:

• Fosfomycin: 3g single oral dose

  • Highly effective against common uropathogens
  • Minimal drug interactions
  • Effective even against vancomycin-resistant enterococci (VRE)
  • Simple one-dose regimen improves adherence

• Nitrofurantoin: 100mg twice daily for 5 days

  • Excellent efficacy against most uropathogens
  • Contraindicated in renal impairment (CrCl <60 mL/min)
  • Avoid in last trimester of pregnancy

• Trimethoprim-sulfamethoxazole: 160/800mg twice daily for 3 days 2, 3

  • Standard adult dosage for UTIs
  • Should be used with caution in areas with resistance rates >10%

Treatment Algorithm Based on Patient Factors

1. For uncomplicated UTIs in otherwise healthy adults:

   • Fosfomycin 3g single dose (preferred)
   • Nitrofurantoin 100mg twice daily for 5 days (alternative)
   • Trimethoprim-sulfamethoxazole 160/800mg twice daily for 3 days (if local resistance <10%)

2. For patients with renal impairment:

   • CrCl >30 mL/min: Standard dosing
   • CrCl 15-30 mL/min: Half the usual regimen
   • CrCl <15 mL/min: Avoid trimethoprim-sulfamethoxazole and nitrofurantoin 2, 3

3. For pregnant women:

   • Nitrofurantoin (avoid in last trimester)
   • Cephalosporins are safe alternatives 1

4. For complicated UTIs or pyelonephritis:

   • Consider intravenous fosfomycin 4g every 6 hours
   • Alternative: Ceftazidime/avibactam 2.5g IV q8h
   • Treatment duration: 5-14 days depending on clinical response 1

Clinical Considerations for Nitrite-Negative UTIs

The nitrite test has high specificity (94%) and positive predictive value (96%), but a negative nitrite test does not rule out infection 4. When the nitrite test is negative but leukocyte esterase is positive, there is still a high probability of UTI (PPV 79%, sensitivity 82%) 4.

Important Caveats:

• A negative nitrite with positive leukocyte esterase test should still be treated as a UTI
• Even when both nitrite and leukocyte esterase tests are negative, approximately 50% of samples may still be culture positive 4
• The most common pathogens in nitrite-negative UTIs include:
  • Enterococci (which don't reduce nitrates)
  • Staphylococcus saprophyticus (more common in younger patients)
  • Some strains of E. coli that don't produce nitrate reductase

Monitoring Response

• Assess clinical response within 48-72 hours of treatment initiation
• Consider follow-up urine culture in complicated cases or treatment failures
• For recurrent UTIs, consider daily antibiotic prophylaxis when non-antimicrobial interventions have failed 1

Antibiotic Resistance Considerations

• Trimethoprim-sulfamethoxazole resistance rates exceed 20% in many regions, limiting its empiric use 4, 5
• Fluoroquinolones (e.g., ciprofloxacin) should be reserved for complicated UTIs or when first-line agents cannot be used, due to concerns about promoting resistance 5, 6
• Local antibiogram data should guide empiric therapy decisions when available