What is the appropriate nitrofurantoin (Macrobid) dosage for an otherwise healthy adult with normal renal function for treating an uncomplicated urinary tract infection and for long‑term prophylaxis?

Macrobid Dosing for Adults

For uncomplicated urinary tract infections in otherwise healthy adults with normal renal function, prescribe nitrofurantoin monohydrate/macrocrystals (Macrobid) 100 mg orally twice daily for 5 days. 1

Treatment Dosing for Uncomplicated Cystitis

• The standard regimen is 100 mg twice daily for 5 days, which achieves clinical cure rates of 88-93% and bacteriological cure rates of 81-92%. 1

• A 7-day course (100 mg twice daily) is acceptable and provides equivalent efficacy (89-93% clinical cure), but extending beyond 5-7 days offers no additional benefit and increases adverse event risk. 1, 2

• Do not use 3-day regimens (100 mg four times daily), as they demonstrate inferior efficacy with only 88% clinical cure and 74% bacterial cure rates. 2

Long-Term Prophylaxis Dosing

For prevention of recurrent UTIs, prescribe 50-100 mg once daily at bedtime. 2, 3

• Prophylaxis can be continued for extended periods (months to years) when indicated, with the duration individualized based on recurrence patterns. 2

• The 50 mg macrocrystalline formulation at bedtime is preferred for long-term use due to better tolerability—only 13% discontinuation rate versus 25.6% with the 50 mg twice-daily microcrystalline formulation. 3

• Long-term prophylaxis reduces symptomatic UTI episodes 5.4-fold, with clinical improvement often maintained for at least 6 months after stopping prophylaxis. 3

Critical Contraindications

Absolute contraindications:

• Creatinine clearance < 30 mL/min: Nitrofurantoin fails to achieve therapeutic urinary concentrations and causes systemic accumulation, leading to irreversible peripheral neuropathy, pulmonary toxicity, and hepatotoxicity. 1, 2

• Suspected pyelonephritis (fever > 38°C, flank pain, costovertebral angle tenderness, nausea/vomiting): The drug does not reach adequate renal tissue concentrations for upper tract infections. 1, 2

Relative caution (CrCl 30-60 mL/min):

• Traditional guidelines recommend avoiding nitrofurantoin when CrCl < 60 mL/min. 4, 2

• However, one retrospective study found 69% efficacy in patients with CrCl 30-60 mL/min when used against susceptible organisms, with only 2 of 26 failures attributable to renal insufficiency. 5

• The safest approach is to avoid nitrofurantoin when CrCl < 60 mL/min and choose trimethoprim-sulfamethoxazole or fosfomycin instead. 2

Special Population: Males

For men with uncomplicated UTI, nitrofurantoin is substantially less effective than in women:

• Males require 100 mg every 6 hours (four times daily) for 7-14 days, with 14 days recommended when prostatitis cannot be excluded. 4

• Clinical failure rates in males are 25% versus only 10-16% in females, representing a clinically meaningful difference. 4

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days or a fluoroquinolone for 5-7 days are preferred alternatives in men. 4

Common Adverse Effects

• Nausea and headache are most common, occurring in 5.6-34% of patients—comparable to trimethoprim-sulfamethoxazole (31-38%). 1, 2

• Serious pulmonary and hepatic toxicity are extremely rare (0.001% and 0.0003% respectively). 1

• Older patients (> 65 years) do not experience higher adverse event rates than younger patients when renal function is adequate. 3

Alternative First-Line Agents (When Nitrofurantoin Cannot Be Used)

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days if local E. coli resistance is < 20% and the patient has not received it in the preceding 3 months. 1, 6

• Fosfomycin 3 g single oral dose provides 90% clinical cure (modestly lower than nitrofurantoin's 95%) and is suitable when renal function is impaired. 1, 2, 6

• 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, 6

• Beta-lactams (amoxicillin-clavulanate, cephalosporins) demonstrate inferior efficacy to nitrofurantoin and should only be used when first-line agents are unsuitable. 1, 6

Clinical Decision Algorithm

Step 1: Confirm uncomplicated lower UTI

• Symptoms limited to dysuria, urgency, frequency, or suprapubic discomfort without fever, flank pain, nausea/vomiting, or costovertebral angle tenderness. 1

Step 2: Verify renal function

• If CrCl ≥ 60 mL/min → nitrofurantoin 100 mg twice daily for 5 days. 1, 2
• If CrCl 30-60 mL/min → choose trimethoprim-sulfamethoxazole or fosfomycin instead. 2, 5
• If CrCl < 30 mL/min → nitrofurantoin is absolutely contraindicated. 1, 2

Step 3: Gender-specific considerations

• Females: Standard 5-day regimen. 1
• Males: Consider 7-14 days at 100 mg four times daily, but recognize 25% failure rate; trimethoprim-sulfamethoxazole or fluoroquinolone may be preferable. 4

Step 4: Rule out upper tract involvement

• Any flank pain, fever, or systemic symptoms → prescribe ciprofloxacin 500 mg twice daily for 5-7 days or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days instead. 1

Common Pitfalls to Avoid

• Do not prescribe nitrofurantoin for "borderline" upper tract symptoms—even mild 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 60 mL/min, and toxicity risk rises sharply 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

• Do not treat asymptomatic bacteriuria in non-pregnant patients or those not undergoing urological procedures. 1