Antibiotic Prophylaxis for Recurrent UTI
For continuous UTI prophylaxis, use trimethoprim-sulfamethoxazole (TMP-SMX) 40 mg/200 mg once daily at bedtime, or nitrofurantoin 50-100 mg once daily for 6-12 months. 1, 2
First-Line Prophylactic Regimens
Continuous Daily Prophylaxis
- TMP-SMX 40 mg/200 mg once daily is the most commonly recommended first-line agent 1
- Nitrofurantoin 50-100 mg once daily is equally effective and preferred when TMP-SMX resistance exceeds 20% or in patients intolerant to sulfa drugs 1, 2
- Both agents demonstrate infection rates of 0.0-0.15 per patient-year compared to 2.8 per patient-year with placebo 3, 4
Alternative Dosing Schedules
- TMP-SMX 40 mg/200 mg three times weekly (Monday-Wednesday-Friday) is effective for patients who prefer less frequent dosing 5
- Post-coital prophylaxis: TMP-SMX 40 mg/200 mg or 80 mg/400 mg as a single dose after intercourse, or nitrofurantoin 50-100 mg post-coitus 1
Duration of Prophylaxis
- Standard duration is 6-12 months with the most robust evidence supporting this timeframe 1, 2
- Prophylaxis effectiveness is limited to the period of active treatment; infection rates return to baseline after discontinuation 4
- Women with ≥3 infections in the year before prophylaxis are more likely to experience recurrence after stopping prophylaxis 3, 4
Critical Contraindications and Monitoring
Nitrofurantoin Restrictions
- Do not use if creatinine clearance <60 mL/min due to inadequate urinary drug concentrations and increased toxicity risk 2
- Avoid in infants <4 months of age due to hemolytic anemia risk 2
- Monitor for pulmonary toxicity (0.001% risk) and hepatic toxicity (0.0003% risk) with regular clinical assessment 2
TMP-SMX Considerations
- Adjust dose for renal impairment: use half the usual dose if creatinine clearance 15-30 mL/min; avoid if <15 mL/min 6
- Consider local resistance patterns—avoid if TMP-SMX resistance exceeds 20% in your region 7
Pre-Prophylaxis Requirements
- Confirm eradication of active UTI with negative urine culture 1-2 weeks after treatment before initiating prophylaxis 1
- Base antibiotic selection on the patient's prior organism susceptibility profiles 2
Alternative Prophylactic Agents
When first-line antibiotics are contraindicated or ineffective:
- Cephalexin (first-generation cephalosporin) 1
- Cefaclor (second-generation cephalosporin) 1
- Fosfomycin (though less studied for prophylaxis) 1
- Fluoroquinolones (norfloxacin, ciprofloxacin) should be reserved for cases where other options have failed due to resistance concerns and side effect profiles 1, 7
Important Clinical Pitfalls
Resistance Patterns
- High resistance rates to TMP-SMX and fluoroquinolones have been documented in U.S.-Mexico border regions and other areas, making them less reliable empiric choices in some geographic locations 7
- Nitrofurantoin maintains favorable resistance profiles across most regions 7
- Emergence of TMP-resistant organisms during prophylaxis is rare (approximately 1-2% of patients) 3, 5
Post-Prophylaxis Considerations
- Non-E. coli infections (Enterococcus, Proteus) occur more frequently after discontinuation of prophylaxis 3
- Approximately 50% of women experience an infection cluster that resolves naturally; prophylaxis does not alter long-term baseline infection rates 4
- Mean time to recurrence after stopping prophylaxis is 2.6 months 5
Cost-Effectiveness
- Prophylaxis becomes cost-effective when baseline infection rate exceeds 2 infections per patient-year 4