Trimethoprim-Sulfamethoxazole for Uncomplicated UTI
For adult women with uncomplicated UTI, prescribe trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg (one double-strength tablet) twice daily for 3 days, but ONLY if your local E. coli resistance rate is below 20%. 1
Critical Decision Point: Check Local Resistance Rates
Before prescribing TMP-SMX empirically, you must verify that local E. coli resistance is <20%. 1 This threshold is non-negotiable because:
- When organisms are susceptible, clinical cure rates are excellent at 90-100% 1
- When organisms are resistant, cure rates plummet to only 41-54%, making treatment failure the expected outcome 1, 2
- In one study from a high-resistance area, microbiologic cure was achieved in only 42% of patients with TMP-SMX-resistant organisms versus 86% with susceptible organisms 2
Important caveat: Hospital antibiograms often overestimate community resistance rates—seek outpatient surveillance data for more accurate guidance. 1
When to Avoid TMP-SMX Empirically
Do not use TMP-SMX if the patient has:
- Used TMP-SMX in the preceding 3-6 months (independently predicts resistance) 1
- Traveled outside the United States in the preceding 3-6 months (independently predicts resistance) 1
- Is in the last trimester of pregnancy (contraindicated) 1
First-Line Alternatives When TMP-SMX Cannot Be Used
If local resistance exceeds 20% or the patient has risk factors for resistance, switch to:
- Nitrofurantoin 100 mg twice daily for 5 days (90% clinical cure, 92% bacterial cure) 1, 3
- Fosfomycin 3g single dose (equally effective with single-dose convenience) 1, 3
These alternatives maintain excellent activity with resistance rates generally below 10% across all regions. 1
Treatment Duration Matters
The 3-day regimen is strongly recommended over longer courses because:
- It achieves equivalent efficacy to longer courses 1
- Each additional day beyond the recommended duration carries a 5% increased risk for antibiotic-associated adverse events without additional benefits 1
- For men with UTI, extend duration to 7 days at the same dose 1
Special Situations
For pyelonephritis: If susceptibility is confirmed, use TMP-SMX 160/800 mg twice daily for 14 days. 1 However, nitrofurantoin is contraindicated for pyelonephritis due to inadequate tissue concentrations—use a fluoroquinolone or other agent with good tissue penetration instead. 3
For renal impairment: The FDA label recommends dose reduction when creatinine clearance is 15-30 mL/min (use half the usual regimen) and avoiding use entirely when <15 mL/min. 4
Common Side Effects to Counsel Patients About
Expect rash, urticaria, nausea, vomiting, and hematologic abnormalities. 1 These occur more frequently than with nitrofurantoin, which produces minimal collateral damage to normal flora. 3
Antimicrobial Stewardship Perspective
Reserve fluoroquinolones (ciprofloxacin, levofloxacin) for pyelonephritis rather than simple cystitis, despite their high efficacy (93-97% bacteriologic eradication), due to concerns about collateral damage and promoting resistance. 1, 3 The FDA has issued warnings about serious safety issues with fluoroquinolones affecting tendons, muscles, joints, nerves, and the central nervous system. 3