What is the appropriate nitrofurantoin (Macrobid) regimen for an adult with an uncomplicated lower urinary‑tract infection who has normal renal function (creatinine clearance ≥ 60 mL/min) and is not pregnant?

Nitrofurantoin (Macrobid) for Uncomplicated Lower UTI

For an adult with uncomplicated lower urinary tract infection and normal renal function (CrCl ≥ 60 mL/min), prescribe nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days. 1

Standard Dosing Regimen

• Nitrofurantoin 100 mg orally twice daily for 5 days is the evidence-based first-line regimen recommended by the Infectious Diseases Society of America (IDSA), European Society for Microbiology and Infectious Diseases (ESCMID), and European Association of Urology. 1

• This 5-day duration balances optimal efficacy (88–93% clinical cure, 81–92% bacteriologic cure) with minimal adverse effects and antibiotic exposure. 1

• Extending therapy beyond 5–7 days provides no additional benefit and increases the risk of adverse events. 1

Critical Contraindications—When NOT to Use Nitrofurantoin

Do not prescribe nitrofurantoin if any of the following are present:

• Suspected pyelonephritis (fever > 38°C, flank pain, costovertebral angle tenderness, nausea/vomiting, or systemic symptoms)—nitrofurantoin does not achieve adequate renal tissue concentrations. 1

• Creatinine clearance < 30 mL/min—efficacy is markedly reduced and risk of peripheral neuropathy increases. 1, 2

• Pregnancy at term (38–42 weeks gestation), labor/delivery, or neonates < 1 month old—risk of hemolytic anemia. 2

• Suspected prostatitis in men—nitrofurantoin does not penetrate prostatic tissue adequately. 1

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

• Fosfomycin trometamol 3 g as a single oral dose—slightly lower efficacy (63% bacteriologic cure vs 74% for nitrofurantoin) but acceptable alternative. 1

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

• Pivmecillinam 400 mg orally twice daily for 5 days—where available. 1

Agents to Reserve or Avoid

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for pyelonephritis or complicated UTIs due to FDA safety warnings (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance rates (≈24%). 1

• Beta-lactams (amoxicillin-clavulanate, cephalosporins) demonstrate inferior efficacy to nitrofurantoin for uncomplicated cystitis and should be used only when first-line agents are unsuitable. 1, 2

• Amoxicillin or ampicillin alone should never be used empirically due to globally high resistance prevalence. 1

Common Clinical Pitfalls to Avoid

• Do not use nitrofurantoin for "borderline" upper-tract symptoms—any flank pain or low-grade fever warrants a fluoroquinolone or cephalosporin instead. 1

• Do not obtain routine post-treatment urine cultures in asymptomatic patients—cultures are indicated only if symptoms persist after therapy or recur within 2 weeks. 1, 2

• Do not treat asymptomatic bacteriuria—antibiotics should not be prescribed for incidental positive cultures in non-pregnant patients without symptoms. 1

• Verify renal function before prescribing—efficacy drops markedly when CrCl falls below 30 mL/min, though emerging evidence suggests nitrofurantoin may be effective in the CrCl 30–60 mL/min range against susceptible organisms. 3

Special Considerations

• Adequate hydration during treatment helps prevent crystal formation. 1

• Most common adverse effects are nausea and headache (5.6–34% incidence); serious pulmonary and hepatic toxicity are extremely rare (0.001% and 0.0003%, respectively). 1

• For recurrent UTIs (≥3 episodes in 12 months), consider prophylactic measures after completing acute therapy, including behavioral modifications and, in postmenopausal women, topical vaginal estrogen. 1

When Symptoms Persist or Recur

• Obtain urine culture with susceptibility testing if symptoms do not resolve by the end of treatment or recur within 2 weeks. 1

• Retreat with a different agent for 7 days (not 3–5 days)—assume resistance to nitrofurantoin and select from alternative first-line options based on culture results. 1

• Consider imaging if symptoms recur within 2 weeks or if risk factors for complicated UTI are present (diabetes, immunosuppression, anatomic abnormalities). 1