What is the role of Co-trimoxazole (trimethoprim/sulfamethoxazole) in the prophylaxis of chronic Urinary Tract Infections (UTI)?

Co-trimoxazole for Chronic UTI Prophylaxis

Co-trimoxazole (trimethoprim-sulfamethoxazole) is an effective option for continuous antimicrobial prophylaxis of recurrent UTIs, but should only be used after non-antimicrobial interventions have failed, given concerns about adverse drug events, antimicrobial resistance, and microbiome disruption. 1

Dosing Regimens

For prophylaxis of recurrent UTIs, co-trimoxazole can be administered as: 1

• Continuous prophylaxis: 40 mg/200 mg once daily OR 40 mg/200 mg three times weekly
• Postcoital prophylaxis: 40 mg/200 mg or 80 mg/400 mg once after intercourse

The thrice-weekly regimen (40 mg trimethoprim/200 mg sulfamethoxazole) has demonstrated an infection incidence of only 0.1 per patient-year during prophylaxis, with minimal emergence of resistant organisms. 2

When to Use Co-trimoxazole

Prioritize Non-Antimicrobial Options First

Before initiating co-trimoxazole prophylaxis, the following interventions should be attempted: 1

• Vaginal estrogen in postmenopausal women (strong recommendation based on 30 RCTs) 1
• Methenamine hippurate 1 g twice daily for patients without incontinence and fully functional bladders 1
• Cranberry products containing proanthocyanidin 36 mg daily 1
• Increased water intake (additional 1.5L daily) in healthy women 1
• Immunoactive prophylaxis to reduce recurrent UTI in all age groups 1

Appropriate Candidates for Antimicrobial Prophylaxis

Use continuous or postcoital antimicrobial prophylaxis when: 1

• Non-antimicrobial interventions have been unsuccessful
• Patient has recurrent UTIs (≥3 UTIs per year or 2 UTIs in last 6 months) 1
• Patient has been counseled regarding possible side effects including antimicrobial resistance 1

Efficacy Evidence

Once-daily antimicrobial prophylaxis with co-trimoxazole (40 mg/200 mg) demonstrated 0.15 infections per patient-year compared to 2.8 infections per patient-year with placebo (P < 0.001). 3 This efficacy was comparable to trimethoprim alone (0.0 infections/patient-year) and nitrofurantoin (0.14 infections/patient-year). 3

Important Caveats and Limitations

Resistance Considerations

Local resistance patterns are critical. For empirical treatment of acute uncomplicated cystitis, co-trimoxazole should only be used when local E. coli resistance is <20%. 1 The threshold for switching from co-trimoxazole to alternative agents is 20% resistance for non-severe infections like cystitis, but drops to 10% for more severe infections. 1

Rising trimethoprim-sulfamethoxazole resistance among uropathogens, particularly outside the United States, has led some guidelines to no longer recommend it as first-choice treatment for acute cystitis. 1

Duration and Recurrence

• Prophylaxis effectiveness is limited to the period antimicrobials are given 3
• After discontinuation, 21 of 32 patients (66%) had recurrent infection within 6 months, with mean time to recurrence of 2.6 months 2
• Women with ≥3 infections in the year before prophylaxis are more likely to develop infections after prophylaxis stops (P < 0.005) 3

Special Populations

Kidney transplant recipients: All should receive UTI prophylaxis with daily trimethoprim-sulfamethoxazole for at least 6 months after transplantation (this also provides Pneumocystis jirovecii pneumonia prophylaxis). 1

Pregnancy: Not recommended in the first trimester (trimethoprim) or last trimester (sulfamethoxazole). 1

Renal impairment: Dose adjustment required when creatinine clearance <30 mL/min; use not recommended when <15 mL/min. 4

Adverse Effects and Resistance Development

Non-E. coli infections may occur more frequently after prophylaxis discontinuation (P < 0.05). 3 However, emergence of trimethoprim-resistant E. coli during prophylaxis is rare. 2, 3 Side effects are generally less frequent with trimethoprim alone compared to co-trimoxazole. 5

Alternative Antimicrobial Options

If co-trimoxazole cannot be used, consider: 1

• Nitrofurantoin: 50-100 mg daily (continuous) or once postcoitus
• Fluoroquinolones: Reserved for important uses other than prophylaxis due to collateral damage concerns 1

For patients with good compliance, self-administered short-term antimicrobial therapy at symptom onset should be considered as an alternative to continuous prophylaxis. 1