What is the recommended dosage of Nitrofurantoin (macrocrystals) for treating uncomplicated Urinary Tract Infections (UTIs)?

Nitrofurantoin Macrocrystals Dosage for Uncomplicated UTI

For uncomplicated urinary tract infections in adults, nitrofurantoin macrocrystals should be dosed at 100 mg orally twice daily for 5 days, as recommended by the Infectious Diseases Society of America (IDSA) and the European Society for Microbiology and Infectious Diseases (ESMID). 1

Standard Adult Dosing

• The preferred regimen is 100 mg twice daily for 5 days, which achieves clinical cure rates of 84-90% and bacterial cure rates of 92% at early follow-up (5-9 days post-treatment). 1
• At 30-day follow-up, clinical cure rates remain robust at 84%, demonstrating sustained efficacy. 1
• A 7-day course (100 mg twice daily) is an acceptable alternative with clinical cure rates of 89-93% and bacterial cure rates of 86%. 1

Why 5 Days Is Preferred Over Other Durations

• Avoid 3-day regimens (100 mg four times daily) due to lower efficacy, with only 88% clinical cure and 74% bacterial cure rates compared to the 5-day regimen. 1
• The 5-day regimen has been shown equivalent to trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) in clinical and microbiological cure rates. 2
• The 7-day regimen shows equivalent efficacy to ciprofloxacin and trimethoprim-sulfamethoxazole when comparing similar duration courses. 1

Special Population Dosing

Pediatric Patients

• For children ≥12 years: Use adult dosing of 100 mg twice daily for 7 days. 1
• For children <12 years: Dose at 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days. 1, 2

VRE (Vancomycin-Resistant Enterococcus) UTIs

• For VRE UTIs specifically: Use 100 mg four times daily (not twice daily). 1, 2

Critical Contraindications

• Do not use nitrofurantoin if creatinine clearance is <60 mL/min, as inadequate urinary drug concentrations prevent bactericidal activity and increase toxicity risk. 1
• Contraindicated if early pyelonephritis is suspected, as nitrofurantoin does not achieve adequate tissue concentrations for upper tract infections. 1, 2

Expected Adverse Effects

• Nausea and headache are the most common adverse effects, occurring in 5.6-34% of patients depending on the study. 1, 2
• These rates are comparable to trimethoprim-sulfamethoxazole (31-38% adverse events). 1

When to Consider Alternative Agents

• If creatinine clearance <60 mL/min: Switch to trimethoprim-sulfamethoxazole or fosfomycin instead. 1
• If local E. coli resistance to trimethoprim-sulfamethoxazole is <20% and the patient has no sulfa allergy: Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is an equivalent alternative. 1
• Fosfomycin 3 g single dose is an alternative first-line option with slightly lower efficacy (90% vs 95% clinical cure for nitrofurantoin). 1

Common Pitfalls to Avoid

• Do not prescribe the 3-day four-times-daily regimen for uncomplicated UTI, as it has inferior bacterial cure rates compared to the 5-day twice-daily regimen. 1
• Do not use in patients with suspected pyelonephritis or upper tract involvement, as tissue penetration is inadequate. 1
• Always verify renal function before prescribing, as nitrofurantoin is ineffective and potentially harmful when CrCl <60 mL/min. 1