What is the first‑line trimethoprim‑sulfamethoxazole dosing for an adult with uncomplicated cystitis who has normal renal function, no sulfa allergy, and is not pregnant?

First-Line Trimethoprim-Sulfamethoxazole Dosing for Uncomplicated Cystitis

For an adult woman with uncomplicated cystitis and normal renal function, prescribe trimethoprim-sulfamethoxazole 160 mg/800 mg (one double-strength tablet) orally twice daily for 3 days, provided local E. coli resistance is below 20%. 1, 2

Dosing by Sex

• Women: One double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily for 3 days 1, 2
• Men: One double-strength tablet twice daily for 7 days (the 3-day regimen is inadequate for males) 1

Efficacy When Susceptible

• Clinical cure rates reach 90-100% when the uropathogen is susceptible to trimethoprim-sulfamethoxazole 1, 2
• Bacterial eradication rates are 91-100% for susceptible organisms 1, 2
• One high-quality study demonstrated 100% clinical cure with the 3-day regimen 1

Critical Resistance Threshold

Do not use trimethoprim-sulfamethoxazole empirically when local E. coli resistance exceeds 20%, because treatment failures outweigh benefits at this threshold. 1, 2, 3

• When organisms are susceptible, cure rates are 84% 2, 3
• When organisms are resistant, cure rates plummet to only 41-54%, making treatment failure the expected outcome 1, 2, 3

Individual Risk Factors That Contraindicate Empiric Use

Avoid empiric trimethoprim-sulfamethoxazole in patients with:

• Recent trimethoprim-sulfamethoxazole use within the preceding 3-6 months (independently predicts resistance) 1
• Recent international travel outside the United States within the preceding 3-6 months (associated with higher resistance rates) 1

Alternative First-Line Agents

When trimethoprim-sulfamethoxazole cannot be used due to resistance or contraindications:

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days achieves 90% clinical cure and 92% bacterial eradication with minimal resistance (generally <10%) 1, 4
• Fosfomycin trometamol 3 g as a single dose offers convenient single-dose therapy with minimal resistance 1
• Ciprofloxacin 250 mg twice daily for 3 days provides 93-97% bacteriologic eradication but should be reserved for cases where first-line agents cannot be used due to concerns about collateral damage and fluoroquinolone resistance 1

Common Pitfalls to Avoid

• Do not rely on hospital antibiograms for community-acquired cystitis; they overestimate resistance because they reflect complicated infections. Use outpatient surveillance data instead. 1
• Do not prescribe the 3-day regimen for men; they require 7 days for adequate cure 1
• Do not use amoxicillin or ampicillin empirically; these agents have very high worldwide resistance rates and demonstrate poor efficacy 1, 2
• Do not use trimethoprim-sulfamethoxazole in the last trimester of pregnancy due to potential fetal risks 1

Renal Dosing Adjustment

The FDA label provides specific guidance for impaired renal function: 5

• Creatinine clearance >30 mL/min: Use the usual standard regimen
• Creatinine clearance 15-30 mL/min: Use half the usual regimen
• Creatinine clearance <15 mL/min: Use is not recommended

Adverse Effects

Common side effects include rash, urticaria, nausea, vomiting, and hematologic abnormalities (thrombocytopenia, neutropenia). 1