What is the appropriate Macrobid (nitrofurantoin) dosing for an uncomplicated urinary tract infection, including adjustments for renal function, pregnancy, and pediatric patients?

Macrobid Dosing for Uncomplicated UTI

Standard Dosing Regimen

For uncomplicated urinary tract infections in adult women, prescribe Macrobid (nitrofurantoin monohydrate/macrocrystals) 100 mg orally twice daily for 5 days. 1

• This 5-day regimen achieves clinical cure rates of 88-93% and bacteriological cure rates of 81-92%, making it the optimal first-line choice recommended by the Infectious Diseases Society of America (IDSA) and European Society for Microbiology and Infectious Diseases (ESCMID). 1
• Extending therapy beyond 5-7 days provides no additional efficacy and increases the risk of adverse events (nausea and headache occur in 5.6-34% of patients). 1, 2
• A 7-day course (100 mg twice daily) is acceptable and shows equivalent efficacy to ciprofloxacin and trimethoprim-sulfamethoxazole, with clinical cure rates of 89-93%. 2

Renal Function Adjustments

Avoid nitrofurantoin when creatinine clearance is below 30 mL/min due to inadequate urinary drug concentrations and increased risk of peripheral neuropathy. 1, 2

• The American Geriatrics Society recommends avoiding nitrofurantoin in older adults with CrCl <30 mL/min due to increased risk of serious toxicities. 1
• For patients with CrCl 30-60 mL/min, recent evidence suggests nitrofurantoin can be used safely and effectively for uncomplicated cystitis, though guideline statements vary in this range. 1, 3
• In a study of hospitalized adults with renal insufficiency (CrCl <60 mL/min), nitrofurantoin eradicated uropathogens in 69% of patients, with only 2 failures attributable to renal insufficiency (both had CrCl <30 mL/min). 3
• When CrCl is <30 mL/min, switch to trimethoprim-sulfamethoxazole (if local E. coli resistance <20%) or fosfomycin 3 g single dose as alternatives. 1, 2

Pregnancy Considerations

Nitrofurantoin is generally safe in pregnancy but should be avoided near term (after 38 weeks) due to theoretical risk of hemolytic anemia in the newborn. 1

• The standard adult dose of 100 mg twice daily for 5-7 days is appropriate for pregnant women with uncomplicated UTI. 1
• Nitrofurantoin is classified as a first-line agent for uncomplicated UTI in pregnancy by major guidelines. 1

Pediatric Dosing

For children ≥12 years, use the adult dose of 100 mg twice daily for 7 days. 1, 2

For children <12 years, prescribe 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days or at least 3 days after obtaining sterile urine. 1, 2

Male UTI Dosing

For men with uncomplicated UTI, prescribe nitrofurantoin 100 mg orally every 6 hours (four times daily) for 7-14 days. 4

• Use 14 days when prostatitis cannot be excluded, as nitrofurantoin does not penetrate prostatic tissue adequately. 1, 4
• Critical caveat: Nitrofurantoin has substantially lower efficacy in males, with a 25% failure rate versus 10-16% in females. 4
• Consider alternative agents (trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days or fluoroquinolones for 5-7 days) as first-line options for men. 4

Special Dosing Situations

For vancomycin-resistant Enterococcus (VRE) UTIs, increase the dose to 100 mg orally four times daily. 1, 2

Critical Contraindications

Never use nitrofurantoin if pyelonephritis is suspected (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting, or systemic symptoms). 1, 2

• Nitrofurantoin does not achieve adequate renal tissue concentrations for upper tract infections. 1
• For suspected pyelonephritis, prescribe ciprofloxacin 500 mg twice daily for 5-7 days or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days instead. 1

Do not use nitrofurantoin for complicated UTIs (structural/functional abnormalities, obstruction, instrumentation, immunosuppression, or history of multidrug-resistant organisms). 1, 4

Alternative First-Line Options When Nitrofurantoin Cannot Be Used

• Fosfomycin 3 g single oral dose is an alternative, though bacteriological cure rates are modestly lower (63% vs 74% for nitrofurantoin at 28 days). 1, 5
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days may be used only if local E. coli resistance is <20% and the patient has not received it in the preceding 3 months. 1, 2

Common Pitfalls to Avoid

• Do not prescribe nitrofurantoin for "borderline" upper-tract symptoms; any flank pain or low-grade fever warrants a fluoroquinolone or cephalosporin. 1
• Always verify renal function before prescribing; efficacy drops markedly when CrCl falls below 30 mL/min. 1, 2
• Routine post-treatment urine cultures are unnecessary for asymptomatic patients; obtain cultures only if symptoms persist after therapy or recur within 2 weeks. 1
• Avoid fluoroquinolones for uncomplicated cystitis due to FDA safety warnings (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance rates (~24%); reserve them for pyelonephritis. 1
• Do not use beta-lactams (amoxicillin-clavulanate, cephalosporins) as first-line agents for uncomplicated cystitis, as they demonstrate inferior efficacy compared to nitrofurantoin. 1

Hydration and Administration

• Patients should ensure adequate hydration during treatment to prevent crystal formation. 1
• Nitrofurantoin can be taken with food to minimize gastrointestinal side effects. 1