Enterococcus faecalis Coverage by Sulfatrim (TMP-SMX)
No, sulfamethoxazole/trimethoprim (Sulfatrim) should NOT be used to treat Enterococcus faecalis infections, despite appearing susceptible on in vitro testing, because enterococci bypass the drug's mechanism by utilizing exogenous folates in vivo, leading to clinical treatment failures and potential bacteremia. 1
Critical Clinical Pitfall: In Vitro vs In Vivo Activity
The most dangerous aspect of TMP-SMX and enterococci is the discordance between laboratory susceptibility and clinical efficacy:
- Laboratory testing may show susceptibility, but this is misleading because standard testing media lacks the folate-rich environment present in human tissues 1
- Clinical failures are well-documented, including two cases where patients with "susceptible" enterococcal UTIs developed bacteremia while on TMP-SMX and only recovered after switching to penicillin or vancomycin plus aminoglycosides 1
- Resistance develops rapidly when TMP-SMX is used for prolonged treatment (>2 weeks), even when organisms initially appear susceptible 2
Why TMP-SMX Fails Against Enterococci
Enterococci possess a unique metabolic capability that renders TMP-SMX ineffective:
- Enterococci can incorporate preformed exogenous folates from the host environment, completely bypassing the antifolate mechanism of TMP-SMX 1
- While sulfonamides alone show universal resistance, and TMP may show some in vitro activity (geometric mean MIC 0.164 mcg/mL for E. faecalis), this does not translate to clinical efficacy 3
- The combination of TMP-SMX may show synergy in laboratory testing with substantially folate-depleted media, but this does not reflect the folate-rich in vivo environment 3
Guideline-Recommended Treatment for E. faecalis
For Serious Infections (Endocarditis, Bacteremia)
- Ampicillin or penicillin G combined with gentamicin is the standard of care, requiring prolonged administration (up to 6 weeks) for synergistic bactericidal effect 4
- Ampicillin is preferred over penicillin as MICs are 2-4 times lower 4
- For high-level aminoglycoside resistance (MIC >500 mg/L), streptomycin may remain active as an alternative 4
For Urinary Tract Infections
- Ampicillin/amoxicillin remains the drug of choice with clinical and microbiological eradication rates of 88.1% and 86% respectively 5
- Nitrofurantoin is FDA-approved specifically for E. faecalis UTIs with resistance rates below 6%, making it an excellent alternative 5, 6, 7
- Fosfomycin 3g single oral dose is FDA-approved for uncomplicated E. faecalis UTIs 5, 6
For Penicillin-Allergic Patients
- Vancomycin (30-60 mg/kg/day IV in 2-3 doses) is recommended for ampicillin-resistant strains or penicillin allergy 4, 5
When Enterococcal Coverage is NOT Needed
For most community-acquired infections, empiric enterococcal coverage is unnecessary unless specific risk factors are present 5:
- Healthcare-associated intra-abdominal infections
- Postoperative infections
- Prior cephalosporin treatment
- Immunocompromised status
- Valvular heart disease or prosthetic intravascular materials
Laboratory Reporting Concerns
Clinical microbiology laboratories should NOT report TMP-SMX susceptibilities for enterococci, as this practice is misleading and potentially dangerous 1. The only reliable susceptibility reporting should focus on penicillins, vancomycin, and aminoglycosides for synergy testing 1.
Bottom Line Algorithm
For confirmed E. faecalis infection:
- First-line: Ampicillin/amoxicillin (for UTI: 500mg PO q8h × 7 days) 5, 6
- Alternative for UTI: Nitrofurantoin 100mg PO q6h × 5-7 days 5, 6
- For serious infections: Ampicillin + gentamicin × 4-6 weeks 4
- For penicillin allergy: Vancomycin 4, 5
- Never use: TMP-SMX, cephalosporins, or fluoroquinolones (46-47% resistance) 5, 6