What is the recommended dosage of nitrofurantoin (macrocrystals) for a patient with a urinary tract infection (UTI) and possible urethritis, considering potential impaired renal function or pregnancy?

Nitrofurantoin Dosing for UTI

For uncomplicated UTI with normal renal function, prescribe nitrofurantoin macrocrystals 100 mg orally twice daily for 5 days. 1, 2

Standard Dosing Regimen

• The recommended dose is nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days, as endorsed by the Infectious Diseases Society of America and European Society for Microbiology and Infectious Diseases 1, 2
• This 5-day regimen achieves clinical cure rates of 84-90% and bacterial cure rates of 92% at early follow-up 2
• A 7-day course (100 mg twice daily) is an acceptable alternative with clinical cure rates of 89-93%, though the 5-day regimen is preferred to minimize antibiotic exposure 1, 2

Critical Contraindications You Must Check

• Do not prescribe nitrofurantoin if creatinine clearance is <60 mL/min - inadequate urinary drug concentrations prevent bactericidal activity and increase toxicity risk 2
• Avoid nitrofurantoin if pyelonephritis is suspected - it does not achieve adequate tissue concentrations for upper tract infections 1, 2
• Contraindicated in the last trimester of pregnancy (though it can be used earlier in pregnancy with caution) 3
• The American Geriatrics Society recommends avoiding nitrofurantoin in older adults with creatinine clearance below 30 mL/min due to increased risk of peripheral neuropathy 1

Special Situations

For Urethritis Concerns

• Nitrofurantoin is appropriate for uncomplicated cystitis but does not adequately treat urethritis - if urethritis is suspected (particularly sexually transmitted), consider alternative agents or additional coverage for Chlamydia/Gonorrhea 1

For Pregnancy

• Nitrofurantoin can be used in early pregnancy but is contraindicated in the last trimester 3
• If used during pregnancy, the standard dose of 100 mg twice daily for 5-7 days applies 1

For Impaired Renal Function

• If CrCl is <60 mL/min, switch to alternative agents such as trimethoprim-sulfamethoxazole (if local resistance <20%) or fosfomycin 3g single dose 2
• Fosfomycin has slightly lower efficacy (90% vs 95% clinical cure) but is a reasonable alternative when nitrofurantoin cannot be used 2

Alternative Dosing (Less Preferred)

• Avoid 3-day regimens (100 mg four times daily) - these show lower efficacy with only 88% clinical cure and 74% bacterial cure rates 2
• For vancomycin-resistant Enterococcus UTIs specifically, use 100 mg four times daily 1, 2

Expected Adverse Effects

• Nausea and headache are most common, occurring in 5.6-34% of patients 1, 2
• These rates are comparable to trimethoprim-sulfamethoxazole (31-38% adverse events) 2
• Serious side effects like pulmonary reactions and polyneuropathy mainly occur with long-term use, not short courses 3

When to Choose Alternative First-Line Agents

• If CrCl <60 mL/min: Use trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (if local E. coli resistance <20%) or fosfomycin 3g single dose 2, 4
• If pyelonephritis suspected: Use fluoroquinolones or trimethoprim-sulfamethoxazole for 7-14 days instead 1, 4
• If male patient with possible prostatitis: Nitrofurantoin does not penetrate prostatic tissue adequately - use fluoroquinolones or trimethoprim-sulfamethoxazole 1

Key Clinical Pearls

• Ensure adequate hydration during treatment to prevent crystal formation 1
• Routine post-treatment urinalysis or cultures are not indicated for asymptomatic patients 1
• If symptoms persist or recur within 2 weeks, obtain urine culture with susceptibility testing and consider retreatment with a 7-day regimen using another agent 1
• Nitrofurantoin maintains excellent activity against E. coli with minimal resistance despite 60+ years of use, making it an ideal first-line agent when renal function is adequate 3, 5