Trimethoprim-Sulfamethoxazole Dosing for Serious UTI in Adults
For a serious urinary tract infection (complicated UTI or pyelonephritis) in an adult with normal renal function, the recommended oral dose is trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) twice daily for 14 days. 1
Standard Dosing for Serious UTI
The FDA-approved dosing for urinary tract infections is one double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 10-14 days. 1
For uncomplicated pyelonephritis specifically, guidelines recommend 14 days of therapy at this same dose (one double-strength tablet twice daily), but only after confirming susceptibility. 2
This dosing achieves clinical cure rates of 90-100% when organisms are susceptible. 3, 2
Critical Distinction: Serious vs. Uncomplicated UTI
The 3-day regimen (one double-strength tablet twice daily for 3 days) is only appropriate for uncomplicated cystitis in women—never for serious infections, pyelonephritis, or UTIs in men. 3, 2
Men with UTI require a minimum of 7 days of therapy at the same dose (one double-strength tablet twice daily), as the 3-day regimen leads to treatment failure. 3, 2
Renal Function Adjustments
Standard dose (one double-strength tablet twice daily) is appropriate when creatinine clearance is >30 mL/min. 1
When creatinine clearance is 15-30 mL/min, reduce to half the usual dose (one single-strength tablet twice daily or half of a double-strength tablet twice daily). 4, 1
Avoid trimethoprim-sulfamethoxazole entirely when creatinine clearance is <15 mL/min. 4, 1
When to Avoid Empiric Use
Do not use trimethoprim-sulfamethoxazole empirically when local E. coli resistance exceeds 20%, as efficacy plummets from 84% to only 41-54% when organisms are resistant. 2
Avoid in patients who used trimethoprim-sulfamethoxazole in the preceding 3-6 months or traveled outside the United States recently, as these factors predict resistance. 2
For serious infections like pyelonephritis, consider initial parenteral therapy with ceftriaxone or an aminoglycoside first if susceptibility is unknown, rather than giving empiric oral therapy. 3
Alternative Agents for Serious UTI
Fluoroquinolones (ciprofloxacin 500 mg twice daily for 7 days) are preferred alternatives for pyelonephritis when trimethoprim-sulfamethoxazole cannot be used, but only if local resistance is <10%. 3, 2
Nitrofurantoin and fosfomycin are not appropriate for serious UTI or pyelonephritis—they are reserved for uncomplicated cystitis only. 3, 2
Common Pitfalls to Avoid
Never use the 3-day regimen for serious infections—this is the most common dosing error and leads to treatment failure. 3
Always dose-adjust when creatinine clearance is <30 mL/min to prevent hyperkalemia, bone marrow suppression, and crystalluria. 3
Ensure adequate hydration (minimum 1.5 liters daily) to prevent crystalluria during therapy. 5
Monitor baseline potassium levels, as trimethoprim blocks potassium excretion and causes hyperkalemia. 5