Nitrofurantoin Dosing for Urinary Tract Infections
For uncomplicated UTIs in women, use nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days, which achieves 88-93% clinical cure rates and is the IDSA-recommended first-line regimen. 1
Standard Dosing by Clinical Scenario
Uncomplicated Cystitis in Women
- Primary regimen: Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days 1
- Alternative formulation: Nitrofurantoin macrocrystals 50-100 mg four times daily for 5 days 1
- Alternative formulation: Nitrofurantoin macrocrystals prolonged release 100 mg twice daily for 5 days 1
The 5-day regimen is equivalent to trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days in both clinical and microbiological cure rates (81-92% bacterial cure) 1. Both IDSA and the European Society for Microbiology and Infectious Diseases consistently recommend 5 days as the optimal duration 1.
Vancomycin-Resistant Enterococcus (VRE) UTIs
UTIs in Males
- Dose: 100 mg orally every 6 hours (four times daily) 2
- Duration: 7-14 days, with 14 days recommended when prostatitis cannot be excluded 2
Critical caveat: Nitrofurantoin has substantially lower efficacy in males, with a 25% failure rate compared to 10-16% failure in females 2. This represents a clinically meaningful difference that should influence antibiotic selection—consider alternative agents like trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days or fluoroquinolones for 5-7 days based on susceptibility testing 2.
Pediatric Dosing
- Children ≥12 years: 100 mg/dose twice daily 1
- Children <12 years: 5-7 mg/kg/day divided into 4 doses, maximum 100 mg/dose 1
- Duration: 7 days or at least 3 days after obtaining sterile urine 1
Critical Contraindications and Precautions
Absolute Contraindications
- Creatinine clearance <60 mL/min: Inadequate urinary drug concentrations and increased risk of peripheral neuropathy 2
- Suspected pyelonephritis: Nitrofurantoin does not achieve adequate tissue concentrations for upper tract infections 1
- Perinephric abscess 1
Important nuance on renal function: While guidelines state CrCl <60 mL/min is a contraindication, research evidence suggests nitrofurantoin remains highly effective in patients with CrCl 30-60 mL/min (69% overall cure rate), with failures primarily occurring only when CrCl <30 mL/min 3. However, follow guideline recommendations in clinical practice given the established safety concerns.
When to Avoid Nitrofurantoin
- Early pyelonephritis suspected: Use alternative agents with better tissue penetration 1
- Complicated UTI risk factors: Obstruction, foreign body, incomplete voiding, immunosuppression, or history of multidrug-resistant organisms 2
- Intrinsically resistant organisms: Proteus species, Pseudomonas, Serratia 3
- Alkaline urine: May reduce efficacy 3
Efficacy and Comparative Data
Clinical Outcomes
- Clinical cure rates: 88-93% for uncomplicated UTIs in women 1
- Bacterial cure rates: 81-92% 1
- Symptomatic improvement: Significant relief within 3 days, sustained through 7 days 4
- Bacteriological cure at 3 days: 81% versus 20% with placebo 4
Nitrofurantoin demonstrates similar clinical cure rates to ciprofloxacin and trimethoprim-sulfamethoxazole when comparing 7-day regimens 1. It remains a first-line agent due to minimal resistance development and limited collateral damage to normal flora 1.
Adverse Effects and Monitoring
Common Side Effects
- Most frequent: Nausea and headache 1
- Overall adverse event rates: 5.6-34% across studies 1
- Mild headache: Occurs in approximately 10.8% of patients 5
- Rash: Occasional cause of discontinuation 5
Monitoring Recommendations
- Clinical response: Assess within 48-72 hours of initiating treatment 2
- Persistent symptoms: Obtain urine culture with susceptibility testing if symptoms do not resolve by end of treatment or recur within 2 weeks 1
- Retreatment: Consider 7-day regimen with another agent if symptoms persist or recur 1
Follow-Up Considerations
Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients 1. This avoids unnecessary testing and potential overtreatment of asymptomatic bacteriuria.
For symptomatic failures, perform urine culture with susceptibility testing and consider alternative agents based on local resistance patterns and patient-specific factors 1, 2.