What is the recommended dose of Nitrofurantoin (antibiotic) for an adult patient with an uncomplicated urinary tract infection (UTI) and normal renal function?

Nitrofurantoin Dosing for Uncomplicated UTI

For adults with uncomplicated UTI and normal renal function, prescribe nitrofurantoin monohydrate/macrocrystals (Macrobid) 100 mg twice daily for 5 days in women and 7 days in men. 1, 2

Standard Dosing Regimen

Women with Uncomplicated UTI

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the preferred first-line regimen, as recommended by the Infectious Diseases Society of America (IDSA), European Society for Microbiology and Infectious Diseases (ESMID), and European Association of Urology. 1, 2
• This 5-day regimen achieves clinical cure rates of 88-93% and bacterial cure rates of 81-92%. 1, 2
• The 5-day duration represents the optimal balance between efficacy and minimizing antibiotic exposure. 1

Men with Uncomplicated UTI

• Prescribe 100 mg twice daily for 7 days in men, based on limited observational data showing men require longer treatment duration. 2, 3

Alternative Nitrofurantoin Formulations

• Nitrofurantoin macrocrystals: 50-100 mg four times daily for 5 days. 1, 2
• Nitrofurantoin macrocrystals prolonged release: 100 mg twice daily for 5 days. 1, 2
• For VRE (vancomycin-resistant Enterococci) UTIs specifically: 100 mg four times daily. 1

Critical Contraindications and Renal Function Considerations

Absolute Contraindication

• Never prescribe nitrofurantoin if creatinine clearance (CrCl) is <60 mL/min, as this leads to inadequate urinary drug concentrations and increased toxicity risk, including peripheral neuropathy. 2, 3
• The FDA maintains this strict contraindication, and checking renal function before prescribing is the most critical step to avoid dangerous errors. 2, 3

Nuanced Evidence on Renal Function

While guidelines maintain the CrCl <60 mL/min contraindication, emerging research suggests nitrofurantoin may be effective in patients with CrCl 30-60 mL/min. One study showed 69% eradication rates in patients with CrCl <60 mL/min, with failures primarily occurring only when CrCl <30 mL/min. 4 However, follow the FDA and guideline recommendations of avoiding use when CrCl <60 mL/min until further evidence emerges. 3

When NOT to Use Nitrofurantoin

Clinical Scenarios to Avoid

• Do not use if pyelonephritis or upper tract infection is suspected, as nitrofurantoin does not achieve adequate renal tissue concentrations. 1, 2
• Do not use for complicated UTIs (structural/functional abnormalities, obstruction, instrumentation, pregnancy). 1
• Do not use in men with suspected prostatitis, as nitrofurantoin does not penetrate prostatic tissue adequately. 1
• Do not use for perinephric abscess. 1

Alternative First-Line Agents When Nitrofurantoin Cannot Be Used

• Fosfomycin trometamol 3 g single dose (slightly lower efficacy than nitrofurantoin). 1, 2
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (only if local E. coli resistance <20% or confirmed susceptibility). 1, 2
• Pivmecillinam 400 mg twice daily for 5 days (where available). 1

Common Side Effects and Safety

• Nausea and headache are the most common side effects, occurring in 5.6-34% of patients. 1, 2
• Severe adverse effects (interstitial pneumonia, peripheral neuropathy, pulmonary reactions, hepatotoxicity) occur infrequently at 0.02-1.5 per 1000 users, with risk increasing with prolonged use. 3, 5
• Ensure adequate hydration during treatment to prevent crystal formation. 1

Follow-Up Recommendations

• Do not order routine post-treatment urinalysis or urine cultures if the patient is asymptomatic. 1, 2, 3
• If symptoms do not resolve by end of treatment or recur within 2 weeks, obtain urine culture with susceptibility testing. 1, 2, 3
• For retreatment, assume resistance to the original agent and use a different antibiotic for 7 days. 1, 2, 3

Special Populations

Pediatric Dosing

• Children ≥12 years: 100 mg twice daily for 7 days. 1, 2
• Children <12 years: 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days. 1, 2

Elderly Patients

• Always check renal function before prescribing in elderly patients, as age-related decline in renal function is common and nitrofurantoin is contraindicated when CrCl <60 mL/min. 3
• For elderly men with preserved renal function (CrCl ≥60 mL/min), use 100 mg twice daily for 7 days. 3