Trimethoprim-Sulfamethoxazole Dosing for Uncomplicated UTI
For uncomplicated urinary tract infections in healthy adult women, prescribe trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) twice daily for 3 days. 1, 2, 3
Standard Dosing Regimen
The FDA-approved dose is 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 3 days for uncomplicated UTI in women 3
This 3-day regimen achieves clinical cure rates of 90-100% when the pathogen is susceptible 2, 4
Bacterial eradication rates are similarly high at 91-100% for susceptible organisms 2
Critical Resistance Threshold
Only use trimethoprim-sulfamethoxazole empirically when local E. coli resistance rates are below 20%. 1, 2
When resistance exceeds 20%, treatment failure rates increase dramatically from 16% to 59% 5
Clinical cure rates plummet to only 41-54% when the organism is resistant, compared to 84-100% for susceptible organisms 2
Hospital antibiograms often overestimate community resistance; use local outpatient surveillance data when available 2
Gender-Specific Dosing Differences
For men with UTI, extend treatment to 7-14 days at the same dose (160/800 mg twice daily) 2, 5
The standard 3-day regimen studied in women is inadequate for male patients and should never be used 5
When to Avoid Empiric Use
Do not prescribe trimethoprim-sulfamethoxazole empirically if: 2
- Patient used trimethoprim-sulfamethoxazole in the preceding 3-6 months
- Patient traveled outside the United States in the preceding 3-6 months
- Local E. coli resistance data shows >20% resistance rates
First-Line Alternatives
When trimethoprim-sulfamethoxazole cannot be used: 1, 2
- Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days (90-92% cure rates) 1, 2
- Fosfomycin trometamol 3 g single dose (convenient single-dose therapy, though slightly inferior efficacy) 1, 4
- Pivmecillinam 400 mg twice daily for 3-7 days (where available in Europe) 1
Common Pitfalls to Avoid
Never use the 10-14 day regimen listed in the FDA label for uncomplicated cystitis—this is outdated; the 3-day regimen is equally effective with fewer adverse effects 1, 6
Do not prescribe fluoroquinolones as first-line therapy for simple cystitis; reserve them for pyelonephritis despite their high efficacy 1, 2
Avoid β-lactams (including amoxicillin-clavulanate) as first-line agents due to inferior efficacy compared to other options 1, 5
Do not use trimethoprim-sulfamethoxazole in the last trimester of pregnancy 2, 5
Renal Dose Adjustments
For patients with impaired renal function: 3
- CrCl >30 mL/min: Standard dose (160/800 mg twice daily)
- CrCl 15-30 mL/min: Reduce to half-dose
- CrCl <15 mL/min: Use not recommended; choose alternative agent
Monitoring and Side Effects
Common adverse effects include rash, urticaria, nausea, vomiting, and hematologic abnormalities 2
Each additional day of antibiotic treatment beyond 3 days carries a 5% increased risk for antibiotic-associated adverse events without additional benefits 2
Monitor for hyperkalemia, especially in patients with renal impairment, as trimethoprim can cause potassium retention 5