Is Bactrim (trimethoprim/sulfamethoxazole) effective against Enterococcus faecalis?

Bactrim Does NOT Work Against Enterococcus Faecalis

No, Bactrim (trimethoprim-sulfamethoxazole) should not be used to treat Enterococcus faecalis infections due to high resistance rates (31.5%) and documented treatment failures with resistance development. 1

Why Bactrim Fails Against E. faecalis

• High clinical resistance rates: A study of E. faecalis isolates from chronic bacterial prostatitis patients showed 31.5% resistance to trimethoprim-sulfamethoxazole, making it unsuitable for empiric therapy 1

• Resistance develops rapidly: Even when initially effective, prolonged treatment (>2 weeks) with trimethoprim-sulfamethoxazole leads to resistance development in E. faecalis strains that are already sulfonamide-resistant 2

• Not recommended by guidelines: Major infectious disease guidelines consistently omit trimethoprim-sulfamethoxazole from recommended regimens for enterococcal infections, instead recommending ampicillin, vancomycin, or linezolid 3, 4

What Actually Works: First-Line Options

Ampicillin is the gold standard for susceptible E. faecalis infections:

• Ampicillin 2 g IV every 4-6 hours for serious infections 4
• High-dose amoxicillin 500 mg orally every 8 hours for less severe infections 4, 5
• Piperacillin-tazobactam can be used when broader polymicrobial coverage is needed 4

For penicillin-allergic patients or resistant strains:

• Vancomycin 30 mg/kg/day IV in 2 divided doses is the primary alternative 3, 4
• Linezolid 600 mg IV/PO every 12 hours for vancomycin-resistant E. faecalis 4
• Daptomycin 8-12 mg/kg/day IV as an alternative for VRE 4

The Laboratory Paradox

While older in vitro studies from 1985 showed that trimethoprim-sulfamethoxazole had synergistic activity against E. faecalis in laboratory conditions 6, this has not translated to clinical efficacy. The key issue is that E. faecalis strains are inherently resistant to sulfonamides, and clinical isolates demonstrate high resistance rates to the combination 1, 2.

Critical Pitfalls to Avoid

• Do not use Bactrim empirically for suspected enterococcal infections—resistance rates are too high and better alternatives exist 1

• Do not use cephalosporins alone for E. faecalis—they have no intrinsic activity against enterococci 4

• Avoid fluoroquinolones as monotherapy despite lower resistance rates (4.8-26.8%), as ampicillin remains superior for susceptible strains 1

• Never rely on old in vitro data showing susceptibility—clinical resistance patterns have evolved significantly, with global meta-analysis showing increasing resistance over time 7

Site-Specific Considerations

For urinary tract infections specifically:

• Ampicillin remains the drug of choice for E. faecalis UTIs 2
• Nitrofurantoin shows 0% resistance and can be considered for uncomplicated cystitis 1, 8
• High-dose amoxicillin (500 mg every 8 hours) is appropriate for uncomplicated cases 4

For healthcare-associated infections:

• Anti-enterococcal coverage is mandatory when E. faecalis is recovered 3
• Empiric coverage should be directed against E. faecalis using ampicillin, piperacillin-tazobactam, or vancomycin based on susceptibility 3