Nitrofurantoin for Uncomplicated UTI
Nitrofurantoin is a first-line agent for uncomplicated lower urinary tract infections (cystitis) and should be dosed at 100 mg four times daily for 5 days in adults. 1, 2
Dosing Recommendations
Adults
- Standard dose: 100 mg orally four times daily (every 6 hours) for 5 days 1, 2
- Take with food to improve absorption and reduce gastrointestinal side effects 2
- The 5-day duration is supported by current European Association of Urology guidelines, with longer courses (>5 days) generally avoided to prevent adverse effects and antimicrobial resistance 2
Pediatric Patients
- Dose: 5-7 mg/kg/day divided every 6 hours for 5 days 2
- For a 38-pound (17.2 kg) child, 25 mg (5 ml of 25 mg/5 ml suspension) every 6 hours is appropriate 2
Position in Treatment Guidelines
Nitrofurantoin is recommended as a first-line agent alongside amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole for uncomplicated lower UTI. 1
The WHO Expert Committee specifically selected nitrofurantoin over fosfomycin based on randomized controlled trials showing significantly greater likelihood of clinical and microbiologic resolution at 28 days, plus lower cost 1. Current guidelines position nitrofurantoin as the preferred drug of choice for uncomplicated cystitis due to robust efficacy evidence and its ability to spare more systemically active agents for other infections 1.
Efficacy Evidence
Nitrofurantoin demonstrates superior outcomes compared to placebo and comparable or better results than alternative agents:
- In bacteriologically proven UTI, nitrofurantoin achieved bacteriological cure in 21/26 patients (81%) at 3 days versus 5/25 (20%) with placebo (NNT = 1.6) 3
- Symptomatic improvement and cure occurred in 27/35 patients (77%) at 3 days versus 19/35 (54%) with placebo (NNT = 4.4) 3
- Nitrofurantoin shows lower treatment failure rates than trimethoprim-sulfamethoxazole, with 0.3% risk of progression to pyelonephritis versus 0.5% for TMP/SMX 4
- Prescription switch rates are lower for nitrofurantoin (12.7%) compared to TMP/SMX (14.3%) 4
Antimicrobial Resistance Profile
Nitrofurantoin maintains excellent activity against common uropathogens despite over 60 years of clinical use:
- E. coli susceptibility remains generally high in both adults and children 1
- Retains good activity against Staphylococcus saprophyticus and Enterococcus species 5
- Does not contribute to R-factor resistance patterns seen with newer antimicrobials 6
- Low frequency of utilization has preserved its high susceptibility profile 7
Important Contraindications and Cautions
Absolute contraindications:
- Renal impairment of any degree (inadequate urinary concentrations achieved) 5
- Last trimester of pregnancy (third trimester/last 3 months) 5
- Patients with creatinine clearance <60 mL/min should not receive nitrofurantoin 5
Serious adverse effects (primarily with long-term use):
- Pulmonary reactions 5
- Polyneuropathy 5
- These risks are substantially lower with short-term therapy (5 days) compared to chronic suppressive use 5
When NOT to Use Nitrofurantoin
Nitrofurantoin should NOT be used for:
- Pyelonephritis or upper urinary tract infections (inadequate tissue penetration) 1
- Severe or complicated UTIs requiring systemic therapy 1
- Patients with risk factors for multidrug-resistant organisms requiring broader coverage 1
For pyelonephritis, ciprofloxacin (mild-to-moderate) or ceftriaxone/cefotaxime (severe) are recommended first-line agents 1.
Follow-up Recommendations
- No routine post-treatment urinalysis or urine cultures needed for asymptomatic patients 2
- If symptoms persist beyond treatment completion or recur within 2 weeks, obtain urine culture with antimicrobial susceptibility testing 2
- For recurrent UTIs, consider preventive strategies including increased fluid intake, proper hygiene, and possibly prophylactic antibiotics if infections are frequent 2