What is the recommended dosage and frequency of Nitrofurantoin (antibiotic) tablets for treating urinary tract infections (UTIs)?

Nitrofurantoin Dosage and Frequency for Urinary Tract Infections

For uncomplicated urinary tract infections (UTIs), nitrofurantoin should be dosed at 100 mg orally every 6 hours for treatment of UTIs due to vancomycin-resistant Enterococcus (VRE), or 100 mg twice daily for 5-7 days for standard uncomplicated UTIs. 1

Dosing Recommendations by Indication

Uncomplicated UTIs in Women

• Nitrofurantoin monohydrate/macrocrystals: 100 mg orally twice daily for 5-7 days 1
  • Clinical efficacy rate: 93% (range 84-95%)
  • Microbiological efficacy rate: 88% (range 86-92%)
  • Common side effects: nausea, headache

UTIs due to Vancomycin-Resistant Enterococcus (VRE)

• Nitrofurantoin: 100 mg orally every 6 hours 1
  • Recommended with weak recommendation, very low quality of evidence
  • Alternative options for VRE UTIs include:
    • Single dose of fosfomycin 3 g orally 1, 2
    • High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg orally/IV every 8 hours 1

Evidence for Efficacy

• Randomized controlled trials have demonstrated that nitrofurantoin is significantly more effective than placebo in achieving both symptomatic relief and bacteriological cure 3

  • After 3 days: 27/35 combined symptomatic improvement/cure with nitrofurantoin vs. 19/35 with placebo
  • Bacteriological cure after 3 days: 21/26 with nitrofurantoin vs. 5/25 with placebo

• Nitrofurantoin (100 mg twice daily for 5 days) has shown equivalent clinical and microbiological cure rates to trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) 1

• In a study comparing nitrofurantoin (50 mg four times daily for 7 days) with single-dose fosfomycin (3 g), clinical and bacteriological cure rates were not significantly different, though more early side effects were reported with fosfomycin 4

Pediatric Dosing

• For children: 5-7 mg/kg/day orally in 4 divided doses 1
• Maximum dose: 100 mg per dose 1

Important Clinical Considerations

• Nitrofurantoin is not recommended for pyelonephritis or perinephric abscess 1
• Recommended treatment duration is 7 days or at least 3 days after obtaining a sterile urine 1
• Recent UK guidelines recommend 3-day courses of nitrofurantoin (100 mg twice daily), though evidence directly supporting this shorter duration is limited 5
• Nitrofurantoin should be taken with food to improve absorption and reduce gastrointestinal side effects 6

Monitoring and Follow-up

• Clinical response should be expected within 3 days of treatment initiation 3
• If symptoms persist beyond 3 days, consider alternative diagnosis or resistant organism 1
• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients 2

Contraindications

• Not recommended in patients with creatinine clearance <30 mL/min 7
• Use with caution in patients with G6PD deficiency due to risk of hemolysis 7
• Not recommended for use in the last trimester of pregnancy due to risk of hemolytic anemia in the newborn 7

Nitrofurantoin remains an important first-line agent for uncomplicated UTIs due to its continued effectiveness against most uropathogens and low rates of resistance development 6, 7.