What is the preferred treatment between Bactrim (trimethoprim/sulfamethoxazole) and Cephalexin for a urinary tract infection (UTI)?

Bactrim vs Cephalexin for UTI Treatment

For uncomplicated UTIs, Bactrim (trimethoprim-sulfamethoxazole) is superior to cephalexin and should be your first-line choice, provided local E. coli resistance rates are below 20%. 1, 2

First-Line Recommendation

Bactrim DS (160/800 mg) twice daily for 3 days is the preferred treatment for uncomplicated cystitis in women, based on the most recent guidelines from the Infectious Diseases Society of America and European Association of Urology. 1, 2

Why Bactrim Over Cephalexin

• Cephalexin is explicitly categorized as a second-line agent with inferior efficacy compared to Bactrim for UTIs. 1
• β-lactams like cephalexin are "less well studied" and have "inferior efficacy and more adverse effects" compared to other UTI antimicrobials including Bactrim. 1
• Cephalexin should only be used "when other recommended agents cannot be used" or "with caution for uncomplicated cystitis." 1
• The WHO Essential Medicines guidelines recommend Bactrim, nitrofurantoin, or fosfomycin as first-choice options—cephalexin is not listed. 1

Critical Resistance Threshold

Do not use Bactrim empirically if local E. coli resistance exceeds 20%. 1, 2

• In areas with high TMP-SMX resistance (>20%), treatment failure rates increase dramatically—one study showed only 42% microbiologic cure with resistant organisms versus 86% with susceptible organisms. 3
• Check your local antibiogram before prescribing—resistance patterns vary significantly by geographic region. 1, 3

Specific Dosing Protocols

For Women with Uncomplicated Cystitis:

• Bactrim DS (160/800 mg) twice daily for 3 days 1, 2
• Clinical cure rates of 85-100% in studies with susceptible organisms 1

For Men with UTIs:

• Bactrim DS twice daily for 7 days (longer duration needed due to potential prostatic involvement) 2

Alternative First-Line Options (When Bactrim Cannot Be Used)

If Bactrim is contraindicated or local resistance is too high, use these alternatives before considering cephalexin:

• Nitrofurantoin 100 mg twice daily for 5 days 1, 2
• Fosfomycin 3 g single dose 1, 2
• Pivmecillinam 400 mg three times daily for 3-5 days (where available) 1, 2

When to Consider Cephalexin

Cephalexin may be appropriate only in these specific scenarios:

• Patient has documented allergy to sulfa drugs and cannot tolerate nitrofurantoin or fosfomycin 1
• Culture results confirm susceptibility to cephalexin 1
• All other first-line agents are contraindicated or unavailable 1

If using cephalexin, expect a 3-7 day treatment course (longer than Bactrim's 3 days). 1

Common Pitfalls to Avoid

• Do not use Bactrim in first or last trimester of pregnancy—choose nitrofurantoin or cephalexin instead. 2
• Do not assume Bactrim will work without knowing local resistance patterns—treatment failure is common in high-resistance areas. 3
• Do not use amoxicillin or ampicillin empirically—global resistance rates now reach 75% (range 45-100%). 1
• Adverse effects occur in 8-31% of patients on Bactrim, though generally less than with cephalexin. 1, 2

Clinical Efficacy Data

The evidence strongly favors Bactrim over cephalexin:

• Bactrim achieves 90-100% early clinical cure rates in multiple randomized trials when organisms are susceptible. 1
• Bactrim demonstrates equivalent efficacy to fluoroquinolones (which are more potent than cephalexin) for uncomplicated UTIs. 1
• β-lactams including cephalexin have consistently shown inferior outcomes in head-to-head comparisons with Bactrim. 1