What is the appropriate nitrofurantoin dosing for an adult with uncomplicated cystitis, including alternative regimens, prophylaxis, pediatric dosing, and renal function limits?

Nitrofurantoin Dosing for Uncomplicated Cystitis in Adults

For uncomplicated cystitis in adult women, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days, which achieves 84-93% clinical cure rates and represents the optimal balance of efficacy and minimal antibiotic exposure. 1, 2

Standard Adult Dosing Regimen

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the IDSA/ESCMID-recommended first-line regimen for uncomplicated UTI in women 3, 1, 2
• This 5-day course achieves clinical cure rates of 84-93% and bacterial cure rates of 86-92% at early follow-up (5-9 days post-treatment) 3, 1, 2
• At 30-day follow-up, clinical cure rates remain robust at 84%, demonstrating sustained efficacy 1
• A 5-day regimen of nitrofurantoin is equivalent to trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days in both clinical and microbiological cure rates 3, 4

Alternative Duration: 7-Day Regimen

• A 7-day course (100 mg twice daily) is acceptable when clinicians prefer longer therapy, with clinical cure rates of 89-93% and bacterial cure rates of 86% 3, 1
• The 7-day regimen shows equivalent efficacy to ciprofloxacin and trimethoprim-sulfamethoxazole when comparing similar duration courses 3, 1
• Avoid extending therapy beyond 7 days, as this provides no additional efficacy and increases adverse event risk 1, 2

Regimens to Avoid

• Do not use 3-day regimens (100 mg four times daily) due to inferior efficacy, with only 88% clinical cure and 74% bacterial cure rates 1
• The four-times-daily dosing schedule also reduces patient adherence compared to twice-daily regimens 1

Prophylaxis Dosing for Recurrent UTI

• For continuous prophylaxis, prescribe 50-100 mg once daily at bedtime for extended periods (months to years) when indicated 1
• Macrocrystalline nitrofurantoin 50 mg at bedtime is the preferred prophylactic regimen based on superior tolerability compared to 50 mg twice daily 5
• The 50 mg once-daily regimen reduces symptomatic UTI episodes 5.4-fold during prophylaxis 5
• Prophylaxis duration should be individualized based on recurrence pattern and medication tolerance 1

Pediatric Dosing

• For children ≥12 years: Use adult dosing of 100 mg twice daily for 7 days (or at least 3 days after obtaining sterile urine) 1, 2
• For children <12 years: Prescribe 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days 1, 2

Male UTI Dosing

• For males with uncomplicated UTI: Prescribe 100 mg every 6 hours (four times daily) for 7-14 days 6
• Use 14-day duration when prostatitis cannot be excluded, as shorter courses have unacceptably high failure rates in males 6
• Be aware that nitrofurantoin has substantially lower efficacy in males (75% success rate) compared to females (84-93% cure rates), representing a clinically meaningful difference 6

Special Population: VRE UTI

• For vancomycin-resistant Enterococcus UTI: Prescribe 100 mg four times daily 1, 2

Critical Renal Function Contraindications

Nitrofurantoin is absolutely contraindicated when creatinine clearance is <30 mL/min due to inadequate urinary drug concentrations, reduced efficacy, and increased risk of peripheral neuropathy 1, 2, 6, 7

The CrCl 30-60 mL/min Gray Zone

• Current guidelines recommend avoiding nitrofurantoin when CrCl <60 mL/min 1, 6
• However, real-world evidence demonstrates that nitrofurantoin remains highly effective in patients with CrCl 30-60 mL/min, with 69% overall cure rates and only 2 of 26 failures attributable to renal insufficiency 7
• In clinical practice, nitrofurantoin can be used cautiously in patients with CrCl 30-60 mL/min when treating susceptible uropathogens and no alternative first-line agents are suitable, but avoid use when CrCl <30 mL/min 7

Absolute Contraindications Beyond Renal Function

• Do not use nitrofurantoin for suspected or confirmed pyelonephritis (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting), as it does not achieve adequate renal tissue concentrations 1, 2
• Contraindicated for perinephric abscess or complicated UTIs with structural abnormalities 1, 2
• Do not use in men with suspected prostatitis, as nitrofurantoin does not penetrate prostatic tissue adequately 1

Common Adverse Effects

• Nausea and headache are the most common side effects, occurring in 5.6-34% of patients 3, 1, 2
• Adverse event rates are comparable to trimethoprim-sulfamethoxazole (31-38%) 3
• Macrocrystalline formulations have better tolerability than microcrystalline formulations, with 13% premature discontinuation versus 25.6% respectively 5

When to Switch to Alternative First-Line Agents

If CrCl <30 mL/min or pyelonephritis is suspected:

• Use trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (uncomplicated cystitis) or 14 days (pyelonephritis) if local E. coli resistance <20% 1, 2
• Use fosfomycin 3 g single dose as an alternative, though it has slightly lower efficacy (90% vs 95% clinical cure for nitrofurantoin) 3, 1, 2
• Reserve fluoroquinolones (ciprofloxacin 500 mg twice daily for 5-7 days) for pyelonephritis or when first-line agents cannot be used 1, 2

Common Pitfalls to Avoid

• Do not prescribe nitrofurantoin for "borderline" upper-tract symptoms (even mild flank pain or low-grade fever); any suspicion of pyelonephritis requires a fluoroquinolone or cephalosporin 2
• Always verify renal function before prescribing; efficacy drops markedly when CrCl falls below 30 mL/min 1, 6, 7
• Do not obtain routine post-treatment urine cultures for asymptomatic patients; cultures are only indicated if symptoms persist after therapy or recur within 2 weeks 2
• Ensure adequate hydration during treatment to prevent crystal formation 2