Nitrofurantoin Macrocrystals Dosing for Uncomplicated UTI
For uncomplicated urinary tract infections in women, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days. 1
Standard Dosing Regimen
The recommended dose is 100 mg orally twice daily for 5 days, as endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Microbiology and Infectious Diseases (ESMID) 2, 1
This 5-day regimen achieves clinical cure rates of 84-90% and bacterial cure rates of 92% at early follow-up (5-9 days post-treatment) 2, 3
At 30-day follow-up, clinical cure rates remain robust at 84%, demonstrating sustained efficacy 2, 3
Alternative Duration Options
A 7-day course (100 mg twice daily) is acceptable if you prefer a longer regimen, with clinical cure rates of 89-93% and bacterial cure rates of 86% 2
The 7-day regimen shows equivalent efficacy to ciprofloxacin and trimethoprim-sulfamethoxazole when comparing similar duration courses 2
Avoid 3-day regimens (100 mg four times daily), as they show lower efficacy with only 88% clinical cure and 74% bacterial cure rates 2
Special Population Dosing
For vancomycin-resistant Enterococcus (VRE) UTIs specifically, use 100 mg four times daily 1
For children ≥12 years, the adult dose of 100 mg twice daily is appropriate 1
For children <12 years, use 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days 1
Critical Contraindications
Do not use nitrofurantoin if creatinine clearance is <60 mL/min, as inadequate urinary drug concentrations prevent bactericidal activity and increase toxicity risk 1, 4
Avoid if early pyelonephritis is suspected, as nitrofurantoin does not achieve adequate tissue concentrations for upper tract infections 1
Contraindicated in the last trimester of pregnancy (last 3 months) 5
Common Pitfalls to Avoid
Do not extend treatment beyond 7 days routinely, as this increases adverse effects without improving efficacy 1
Do not use the immediate-release formulation at 50-100 mg four times daily for acute treatment unless specifically treating VRE; the macrocrystal/monohydrate formulation twice daily is preferred for better tolerability 1
Ensure the urine pH is not alkaline, as nitrofurantoin efficacy decreases in alkaline urine 6
Avoid prescribing for organisms intrinsically resistant to nitrofurantoin (Proteus species, Pseudomonas, Serratia) 6
Expected Adverse Effects
Nausea and headache are most common, occurring in 5.6-34% of patients depending on the study 2, 1
These rates are comparable to trimethoprim-sulfamethoxazole (31-38% adverse events) 2
Serious pulmonary reactions and polyneuropathy are rare with short-term therapy but increase with long-term use 5
When to Consider Alternative Agents
If local E. coli resistance to trimethoprim-sulfamethoxazole is <20% and the patient has no sulfa allergy, trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is an equivalent alternative 2, 1
If the patient has impaired renal function (CrCl <60 mL/min), switch to trimethoprim-sulfamethoxazole or fosfomycin instead 1, 4
Fosfomycin 3 g single dose is an alternative first-line option with slightly lower efficacy (90% vs 95% clinical cure for nitrofurantoin) 2, 1