What is the appropriate dose of trimethoprim‑sulfamethoxazole (TMP‑SMX) for an uncomplicated urinary tract infection in an otherwise healthy adult?

Sulfamethoxazole-Trimethoprim Dosing for UTI

For uncomplicated UTI in women, give one double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) twice daily for 3 days; for men, use the same dose but extend treatment to 7 days. 1, 2

Standard Dosing by Patient Population

Women with Uncomplicated Cystitis

• One double-strength tablet (800/160 mg) orally twice daily for 3 days is the evidence-based regimen, achieving 90–100% clinical cure rates when organisms are susceptible 1, 2
• This 3-day course provides bacterial eradication rates of 91–100% for susceptible pathogens 1
• The FDA label specifies 10–14 days for UTI, but guideline societies uniformly recommend the shorter 3-day course for uncomplicated cystitis in women based on superior evidence 3, 1

Men with Uncomplicated Cystitis

• One double-strength tablet (800/160 mg) orally twice daily for 7 days is required 1, 4
• The 3-day regimen studied in women is inadequate for men and should never be used 1
• Some sources suggest 7–14 days; 7 days is reasonable for straightforward cases, reserving 14 days for complicated presentations 4

Pyelonephritis (Either Sex)

• One double-strength tablet (800/160 mg) orally twice daily for 14 days, but only after confirming susceptibility 1
• High renal tissue levels make this appropriate for upper tract infections when the organism is susceptible 5

Critical Resistance Threshold

Do not use sulfamethoxazole-trimethoprim empirically when local E. coli resistance exceeds 20%. 1, 2

• When organisms are susceptible, cure rates reach 84–90%; when resistant, cure rates plummet to 41–54%, making treatment failure the expected outcome 1, 2
• This 20% cutoff is derived from expert consensus integrating clinical outcomes, in-vitro data, and mathematical modeling 1

Individual Risk Factors for Resistance

• Recent sulfamethoxazole-trimethoprim use within 3–6 months independently predicts resistance and contraindicates empiric use 1
• International travel outside the United States within 3–6 months increases resistance risk and should prompt alternative therapy 1, 4

Renal Dose Adjustments

• CrCl >30 mL/min: Standard dose (one double-strength tablet twice daily) 3
• CrCl 15–30 mL/min: Reduce to half-dose (one single-strength tablet or half of double-strength tablet) 3
• CrCl <15 mL/min: Use not recommended; select an alternative agent 3

Alternative First-Line Agents When Sulfamethoxazole-Trimethoprim Cannot Be Used

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days achieves 90% clinical cure and 92% bacterial cure with resistance rates generally <10% 1
• Fosfomycin trometamol 3 g single dose offers convenient single-dose therapy with minimal resistance, though slightly lower efficacy than multi-day regimens 1, 4
• Ciprofloxacin 250 mg twice daily for 3 days (women) or 500 mg twice daily for 7 days (men or pyelonephritis) provides 93–97% eradication rates but should be reserved for cases where first-line agents cannot be used due to collateral damage concerns 1

Common Pitfalls to Avoid

• Do not prescribe the 3-day regimen for men—this is the most common dosing error and leads to treatment failure 1
• Do not rely on hospital antibiograms for community-acquired cystitis—they overestimate resistance because they reflect complicated infections; outpatient surveillance data are more accurate 1
• Do not use amoxicillin or ampicillin empirically—worldwide resistance rates are very high and efficacy is poor 4, 5
• Do not fail to adjust dose when CrCl <30 mL/min—this significantly increases toxicity risk, particularly hyperkalemia from the trimethoprim component 3

Pregnancy Considerations

• Avoid in the last trimester due to potential fetal risks 1, 4
• Trimethoprim alone should not be used in the first trimester 4

Monitoring in Renal Impairment

• Obtain baseline creatinine clearance before initiating therapy 4
• Monitor electrolytes regularly, as trimethoprim can cause hyperkalemia 4
• Check serum creatinine and BUN 2–3 times weekly during therapy in patients with renal impairment 4
• Ensure adequate hydration (at least 1.5 liters daily) to prevent crystalluria 4