Is Enterococcus faecalis susceptible to Bactrim (trimethoprim/sulfamethoxazole)?

Enterococcus faecalis is Intrinsically Resistant to Bactrim (Trimethoprim-Sulfamethoxazole)

Enterococcus faecalis should not be treated with Bactrim (trimethoprim-sulfamethoxazole) due to intrinsic resistance, despite potential misleading in vitro susceptibility results. This resistance is well-documented in clinical guidelines and research evidence.

Mechanism of Intrinsic Resistance

Enterococcus faecalis possesses intrinsic resistance to trimethoprim-sulfamethoxazole through a unique mechanism:

• E. faecalis can incorporate preformed exogenous folates, allowing it to bypass the antifolate activity of trimethoprim-sulfamethoxazole in vivo 1
• This creates a dangerous discrepancy where the organism may appear susceptible in laboratory testing but remains resistant in clinical settings

Evidence Supporting Intrinsic Resistance

Multiple sources confirm this intrinsic resistance:

• The Praxis Medical Insights guidelines explicitly state that "E. faecalis is intrinsically resistant to trimethoprim-sulfamethoxazole" 2
• A 2013 study found that 31.5% of E. faecalis strains from chronic bacterial prostatitis showed resistance to trimethoprim-sulfamethoxazole 3
• A concerning case report documented two patients who developed bacteremia while being treated with trimethoprim-sulfamethoxazole for uncomplicated enterococcal UTIs based on misleading in vitro susceptibility results 1

Recommended Alternative Treatments

For E. faecalis infections, guidelines recommend:

1. First-line treatment: Ampicillin (2g IV every 4 hours) or penicillin G 2

   • For serious infections like endocarditis, combination therapy with aminoglycosides is recommended 4

2. For penicillin-allergic patients: Vancomycin (30 mg/kg/day IV in 2 divided doses) 4

3. For vancomycin-resistant E. faecalis:

   • Linezolid 600 mg IV/PO every 12 hours 4
   • Daptomycin 8-12 mg/kg/day (higher doses for serious infections) 4, 2
   • Tigecycline for intra-abdominal infections 4

Clinical Pitfalls to Avoid

1. Laboratory testing discrepancy: Although E. faecalis may appear susceptible to trimethoprim-sulfamethoxazole in vitro, this does not translate to clinical efficacy 1

2. Misinterpretation of susceptibility reports: Clinical microbiology laboratories reporting susceptibilities of enterococci to drugs other than penicillins or vancomycin can be misleading and potentially dangerous 1

3. Inappropriate empiric therapy: Despite trimethoprim-sulfamethoxazole being commonly prescribed empirically for infections like UTIs, it should not be used for E. faecalis infections 3

Conclusion

Despite some older studies suggesting potential in vitro activity of trimethoprim-sulfamethoxazole against E. faecalis 5, 6, the clinical evidence and current guidelines are clear that this combination should not be used for treating E. faecalis infections due to intrinsic resistance mechanisms that allow the organism to escape the drug's effects in vivo. Appropriate alternatives include ampicillin, vancomycin, linezolid, or daptomycin depending on susceptibility patterns and the site of infection.