Nitrofurantoin for Uncomplicated Urinary Tract Infections
For uncomplicated UTIs in women, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days as first-line therapy. 1, 2
Dosing Regimens
Standard Dosing for Uncomplicated UTI
- Nitrofurantoin monohydrate/macrocrystals: 100 mg twice daily for 5-7 days is the recommended first-line treatment 1, 2
- The 5-day regimen is optimal and endorsed by both the Infectious Diseases Society of America (IDSA) and European guidelines 2
- Clinical cure rates range from 88-93% and bacterial cure rates from 81-92% 2
Alternative Formulations
- Nitrofurantoin macrocrystals: 50-100 mg four times daily for 5 days 2
- Nitrofurantoin macrocrystals prolonged release: 100 mg twice daily for 5 days 2
Special Populations
- VRE (vancomycin-resistant enterococci) UTIs: 100 mg four times daily 1, 2
- Pediatric patients ≥12 years: 100 mg twice daily for 7 days 2
- Pediatric patients <12 years: 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days 2
Treatment Duration Considerations
Do not treat for longer than 7 days unless symptoms persist 1, 2. The evidence strongly supports:
- 5-day regimens are equivalent to 3-day trimethoprim-sulfamethoxazole courses 2
- 3-day nitrofurantoin regimens show diminished efficacy (61-70% clinical cure) and should be avoided 3
- 7-day regimens show equivalence to ciprofloxacin and trimethoprim-sulfamethoxazole 2
Efficacy and Comparative Data
Nitrofurantoin demonstrates robust efficacy with minimal resistance development 1, 3:
- Clinical cure rates: 79-92% across studies 3
- Bacteriological cure at 3 days: 81% versus 20% with placebo (NNT = 1.6) 4
- Symptomatic improvement at 3 days: 77% versus 54% with placebo (NNT = 4.4) 4
- Maintains activity against drug-resistant uropathogens including E. coli, Staphylococcus saprophyticus, and Enterococcus species 5, 6
Critical Contraindications
Absolutely avoid nitrofurantoin in these situations 2, 5:
- Suspected pyelonephritis or early upper tract involvement 2
- Renal impairment of any degree 5
- Last trimester of pregnancy (final 3 months) 5
- Perinephric abscess 2
Adverse Effects Profile
Nitrofurantoin is generally well-tolerated with short-term use 3:
- Adverse event rates: 5.6-34% across studies 2
- Most common: nausea and headache 2
- Toxicity is predominantly gastrointestinal, mild, and reversible 3
- Serious pulmonary reactions and polyneuropathy occur mainly with long-term use, not short courses 5
- Meta-analyses show no difference in adverse events compared to other antibiotics 3
Position in Treatment Algorithm
Nitrofurantoin is a first-line agent alongside trimethoprim-sulfamethoxazole and fosfomycin 1. Selection should be based on:
- Local antibiogram patterns 1
- Minimal collateral damage (less disruption of normal flora compared to fluoroquinolones) 1, 2
- Low resistance rates despite 60+ years of use 5, 6
Follow-Up Management
- Do not perform routine post-treatment urinalysis or cultures in asymptomatic patients 2
- If symptoms persist or recur within 2 weeks: obtain urine culture with susceptibility testing 2
- For treatment failure: retreat with a 7-day regimen using an alternative agent based on culture results 2
Common Pitfalls to Avoid
- Do not use 3-day regimens—they have significantly reduced efficacy 3
- Do not prescribe if pyelonephritis is suspected—nitrofurantoin does not achieve adequate tissue concentrations outside the urinary tract 2
- Do not use in patients with any degree of renal dysfunction—the drug requires adequate renal function for urinary concentration 5
- Do not treat asymptomatic bacteriuria (except in pregnant women or before invasive urologic procedures) 1