Nitrofurantoin Dosing for Uncomplicated UTI
For uncomplicated urinary tract infections in women, nitrofurantoin should be dosed at 100 mg twice daily (bd), not once daily, for 5 days. 1
Standard Dosing Regimen for Women
The Infectious Diseases Society of America (IDSA) and European Society for Microbiology and Infectious Diseases (ESMID) consistently recommend nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days as first-line therapy for uncomplicated UTIs in women. 1
The twice-daily dosing achieves clinical cure rates of 88-93% and bacterial cure rates of 81-92% for uncomplicated UTIs. 1
The European Association of Urology similarly endorses 100 mg twice daily for 5 days as first-line treatment for uncomplicated cystitis in women. 1
Why Twice Daily, Not Once Daily?
Once-daily dosing of nitrofurantoin is not supported by any major guideline or clinical evidence for uncomplicated UTIs. 1
The monohydrate/macrocrystal formulation (Macrobid) is specifically designed for twice-daily dosing due to its dual-release properties, which maintain adequate urinary drug concentrations throughout the day. 2
Alternative formulations like macrocrystals may require even more frequent dosing (50-100 mg four times daily), but the sustained-release formulation allows for the more convenient twice-daily regimen. 1, 2
Special Dosing Considerations
For vancomycin-resistant Enterococci (VRE) UTIs or enterococcal infections, increase frequency to 100 mg four times daily (every 6 hours). 1, 2
For males with uncomplicated UTI, European Urology recommends 100 mg every 6 hours (four times daily) for 7-14 days, though efficacy in males is substantially lower with a 25% failure rate compared to 10-16% in females. 3
Duration of Therapy
The standard 5-day course is recommended by IDSA/ESMID and has equivalent efficacy to trimethoprim-sulfamethoxazole 3-day regimens. 1
While some UK guidelines suggest 3-day courses, there is limited direct evidence supporting this shorter duration, and international consensus favors 5 days. 4, 1
Duration should not be extended beyond 7 days unless symptoms persist, as shorter courses minimize adverse effects while maintaining efficacy. 1
Critical Contraindications
Do not use nitrofurantoin if creatinine clearance is <60 mL/min due to inadequate urinary drug concentrations and increased risk of peripheral neuropathy. 3, 2
Avoid if early pyelonephritis is suspected, as nitrofurantoin does not achieve adequate tissue penetration for upper tract infections. 1, 3
Contraindicated in the last trimester of pregnancy. 2
Common Pitfalls
Never prescribe once-daily dosing—this is not evidence-based and will result in subtherapeutic urinary concentrations. 1, 2
Do not use in males without recognizing the significantly higher failure rate (25%) and consider alternative agents or longer duration with more frequent dosing. 3
Nausea and headache are the most common side effects, occurring in 5.6-34% of patients, which may affect compliance with the twice-daily regimen. 1, 2