Is Zosyn (piperacillin/tazobactam) effective against enterococcus?

Zosyn (Piperacillin/Tazobactam) Coverage for Enterococcus

Zosyn (piperacillin/tazobactam) has limited activity against enterococci, with good coverage only for Enterococcus faecalis but not for Enterococcus faecium or other resistant enterococcal species.

Enterococcal Coverage Specifics

Enterococcus faecalis

• Zosyn generally provides adequate coverage against E. faecalis, particularly beta-lactamase-producing strains 1
• Tazobactam (the beta-lactamase inhibitor in Zosyn) successfully reverses the inoculum effect seen with beta-lactamase-producing E. faecalis 1
• Time-kill studies have demonstrated bactericidal activity against beta-lactamase-producing E. faecalis when piperacillin is combined with tazobactam 1

Enterococcus faecium

• Zosyn has poor activity against E. faecium 2
• E. faecium is specifically listed as a resistant organism to piperacillin/tazobactam in drug evaluations 2
• Clinical guidelines do not recommend Zosyn for infections where E. faecium is suspected or confirmed

Clinical Implications

For Empiric Therapy

• When enterococcal coverage is needed and the species is unknown, Zosyn alone is insufficient due to its poor activity against E. faecium
• For serious infections where enterococcal coverage is critical (such as endocarditis), guidelines recommend:
  • Ampicillin or penicillin G plus gentamicin for susceptible strains 3
  • Vancomycin plus gentamicin for penicillin-resistant strains 3
  • Double β-lactam regimens (ampicillin plus ceftriaxone) for high-level aminoglycoside-resistant E. faecalis 3

For Confirmed Enterococcal Infections

• For E. faecalis: Zosyn may be effective, especially for beta-lactamase-producing strains 1
• For E. faecium: Alternative therapy is required, such as:
  • Vancomycin (if susceptible) 3
  • Linezolid (600 mg IV/PO every 12h) 3
  • Daptomycin (high dose 8-12 mg/kg/day) 3

Special Considerations

Combination Therapy

• For serious enterococcal infections, Zosyn alone is generally insufficient
• When used for enterococcal infections, Zosyn may be more effective when combined with an aminoglycoside (if not high-level aminoglycoside resistant) 1
• In a study of spontaneous bacterial peritonitis, the combination of Zosyn plus linezolid showed fewer treatment failures than Zosyn alone, suggesting benefit when covering for resistant Gram-positive organisms including E. faecium 4

Resistance Patterns

• Surveillance data shows that while E. faecalis generally remains susceptible to Zosyn (96% susceptibility in one large study), resistance rates are increasing 5
• The prevalence of E. faecium, which is inherently resistant to Zosyn, has increased in hospital settings 5

Clinical Decision Algorithm

1. If treating empirically and enterococcal infection is suspected:

   • If low risk for E. faecium: Zosyn may provide adequate coverage
   • If high risk for E. faecium (e.g., healthcare-associated infection, prior antibiotics): Add agent with E. faecium activity

2. If enterococcal species is known:

   • E. faecalis: Zosyn is generally appropriate
   • E. faecium: Choose alternative therapy (vancomycin, linezolid, or daptomycin)

3. For serious enterococcal infections (e.g., endocarditis, bacteremia):

   • Follow specific guideline-recommended regimens 3
   • Consider infectious disease consultation 3

In summary, while Zosyn provides reasonable coverage against E. faecalis, it should not be relied upon for coverage of E. faecium or for serious enterococcal infections where more specific and proven regimens are recommended by clinical guidelines.