What is the coverage and dosage of Macrobid (Nitrofurantoin) for urinary tract infections?

Macrobid (Nitrofurantoin) Coverage and Dosing

Macrobid provides excellent coverage for uncomplicated urinary tract infections caused by E. coli, Staphylococcus saprophyticus, and Enterococcus species (including VRE), with the standard dose being 100 mg twice daily for 5-7 days in women and 7-14 days in men. 1

Spectrum of Coverage

Nitrofurantoin maintains robust activity against the most common uropathogens despite over 60 years of clinical use:

• E. coli: Remains highly susceptible with minimal resistance development, making nitrofurantoin a fluoroquinolone-sparing first-line option 1, 2
• Staphylococcus saprophyticus: Inherently susceptible and responds well to standard treatment without requiring susceptibility testing 1
• Enterococcus species: Effective coverage including vancomycin-resistant enterococci (VRE), though VRE requires higher dosing at 100 mg four times daily 1
• Other susceptible organisms: Some additional gram-negative and gram-positive uropathogens 3, 2

Dosing Regimens by Patient Population

Women with Uncomplicated Cystitis (Standard Dosing)

• 100 mg twice daily for 5-7 days is the IDSA-recommended first-line regimen 1, 4
• The 5-day regimen achieves 88-93% clinical cure rates and 81-92% bacterial cure rates 1
• This 5-day course is equivalent to trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days 1, 5

Alternative formulation: Nitrofurantoin macrocrystals can be dosed at 50-100 mg four times daily for 5 days 1

Men with UTI (Extended Duration Required)

• 100 mg every 6 hours for 7-14 days, with 14 days recommended when prostatitis cannot be excluded 6
• Critical caveat: Clinical efficacy in males is substantially lower than in females, with a 25% failure rate in males versus 10-16% failure in females 6
• Due to this higher failure rate, consider alternative agents (trimethoprim-sulfamethoxazole or fluoroquinolones) as first-line for male UTIs unless susceptibility data supports nitrofurantoin use 6

Special Populations

• VRE infections: 100 mg four times daily for standard UTI duration 1
• Pediatric patients ≥12 years: 100 mg twice daily 1
• Pediatric patients <12 years: 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days 1

Critical Contraindications and Limitations

Absolute Contraindications

• Creatinine clearance <60 mL/min: Inadequate urinary drug concentrations and increased risk of peripheral neuropathy 6
• Suspected pyelonephritis or upper tract involvement: Nitrofurantoin does not achieve adequate tissue concentrations outside the bladder 1, 6
• Last trimester of pregnancy (final 3 months): Risk of hemolytic anemia in the newborn 2
• Perinephric abscess: Not recommended 1

When to Choose Alternative Agents

Do not use nitrofurantoin if the patient has:

• Risk factors for complicated UTI (obstruction, foreign body, incomplete voiding, immunosuppression) 6
• Systemic symptoms suggesting invasive infection 6
• Male gender with first UTI episode (consider alternatives due to 25% failure rate) 6

Comparative Efficacy and Clinical Context

Nitrofurantoin's resurgence as a first-line agent is driven by:

• Minimal resistance development: Unlike trimethoprim-sulfamethoxazole and fluoroquinolones, resistance rates remain low despite decades of use 1, 2
• Limited collateral damage: Does not promote resistance in other bacterial populations 1
• Equivalent efficacy to other first-line agents: Similar clinical cure rates (90%) to trimethoprim-sulfamethoxazole when comparing 5-day nitrofurantoin to 3-day trimethoprim-sulfamethoxazole regimens 1, 5

Common Pitfalls to Avoid

• Do not extend treatment beyond 7 days in women unless symptoms persist, as shorter courses minimize adverse effects while maintaining efficacy 1
• Do not use for systemic infections: Nitrofurantoin concentrates in urine but does not achieve therapeutic levels in blood or tissues 6
• Do not prescribe without checking renal function: Even mild renal impairment (CrCl <60) is a contraindication 6
• Monitor for pulmonary reactions and polyneuropathy with long-term use, though these are rare with short-course therapy 2

Adverse Effects

• Most common: Nausea and headache, with adverse event rates ranging from 5.6-34% across studies 1
• Serious but rare: Pulmonary reactions and peripheral neuropathy, primarily with long-term use 2