Nitrofurantoin for Uncomplicated Urinary Tract Infections
Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the recommended first-line treatment for uncomplicated UTIs in women. 1, 2
Dosing Regimens
Standard Dosing
- Nitrofurantoin monohydrate/macrocrystals: 100 mg twice daily for 5-7 days 1, 2
- The 5-day regimen is optimal and endorsed by both the Infectious Diseases Society of America (IDSA) and European Society for Microbiology and Infectious Diseases (ESMID) 2
- Alternative formulation: Nitrofurantoin macrocrystals 50-100 mg four times 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 extend treatment beyond 7 days unless symptoms persist. 1, 2
- The 5-day regimen achieves equivalent clinical and microbiological cure rates to trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) 2
- Clinical cure rates range from 88-93% with nitrofurantoin 2
- Bacterial cure rates range from 81-92% 2
- Avoid 3-day regimens: Clinical efficacy drops to 61-70% with only 3 days of treatment 3
Efficacy Evidence
The evidence strongly supports nitrofurantoin's effectiveness:
- In placebo-controlled trials, nitrofurantoin achieved combined symptomatic improvement and cure in 27/35 patients versus 19/35 with placebo at 3 days (NNT = 4.4) 4
- Bacteriological cure at 3 days was 21/26 with nitrofurantoin versus 5/25 with placebo (NNT = 1.6) 4
- Meta-analyses show overall equivalence to comparator drugs (trimethoprim-sulfamethoxazole, ciprofloxacin, amoxicillin) in clinical cure, with only slight disadvantage in microbiological efficacy (RR 0.93,95% CI 0.89-0.97) 3
Why Nitrofurantoin is First-Line
Nitrofurantoin minimizes collateral damage and maintains excellent susceptibility despite decades of use. 1, 5
- Resistance rates remain remarkably low at 2.3% for E. coli, compared to 24% for fluoroquinolones and 29% for trimethoprim-sulfamethoxazole 5
- Maintains 95.6% susceptibility against E. coli uropathogens 5
- Inherently active against Staphylococcus saprophyticus and Enterococcus species 6, 2
- Less likely to produce collateral damage than second-line agents 1
Critical Contraindications
Do not use nitrofurantoin if early pyelonephritis is suspected or in patients with any degree of renal impairment. 2, 6
- Contraindicated in the last three months of pregnancy 6
- Not recommended for perinephric abscess 2
- Avoid if creatinine clearance is reduced 6
Adverse Effects
Toxicity is generally mild and predominantly gastrointestinal:
- Nausea and headache are most common 2
- Adverse event rates range from 5.6-34% across studies 2
- Meta-analyses confirm no difference in adverse events compared to other antibiotics 3
- Serious side effects (pulmonary reactions, polyneuropathy) occur mainly with long-term use, not short-term therapy 6, 3
Clinical Management Algorithm
- Obtain urine culture and sensitivity before initiating treatment 1
- Start nitrofurantoin 100 mg twice daily for 5 days 2
- Do not perform routine post-treatment urinalysis or cultures if asymptomatic 2
- If symptoms persist or recur within 2 weeks: Obtain urine culture with susceptibility testing and retreat with a 7-day regimen using another agent 2
Alternative First-Line Options When Nitrofurantoin Cannot Be Used
- Fosfomycin trometamol 3 g single dose (slightly lower efficacy than nitrofurantoin) 2
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (only if local E. coli resistance <20%) 1, 2
- Pivmecillinam 400 mg twice daily for 5 days (where available) 2
Common Pitfall to Avoid
Do not treat asymptomatic bacteriuria. 1 Surveillance urine testing should be omitted in asymptomatic patients with recurrent UTIs, and asymptomatic bacteriuria should not be treated except in pregnant women or patients scheduled for invasive urinary procedures 1.