Does Zosyn Cover VRE?
No, Zosyn (piperacillin-tazobactam) does not provide reliable coverage against Vancomycin-Resistant Enterococcus (VRE) and should not be used for treatment of documented VRE infections.
Recommended Treatment for VRE
When VRE is documented or strongly suspected, the appropriate antimicrobial agents are:
- Linezolid is the treatment of choice for monomicrobial VRE infections 1
- Tigecycline is appropriate for polymicrobial infections involving VRE 1
- Daptomycin can be considered for complicated VRE infections when other options fail, though it is primarily reserved for more serious infections 2, 3
Why Piperacillin-Tazobactam Fails Against VRE
While piperacillin-tazobactam has some activity against vancomycin-susceptible Enterococcus faecalis, it lacks reliable activity against vancomycin-resistant strains:
- The majority of VRE infections are caused by E. faecium, which has acquired glycopeptide resistance mechanisms that also confer resistance to many beta-lactams 1
- Although piperacillin-tazobactam can be used for susceptible E. faecalis when confirmed by susceptibility testing 1, this does not extend to VRE strains 3
Clinical Context: When to Suspect VRE
VRE should be suspected in patients with specific risk factors:
- Previous antibiotic therapy (especially prolonged courses) 1
- Prolonged hospitalization or ICU stay 1
- Severe underlying illness or immunocompromised state 1
- Recent gastrointestinal surgery or invasive procedures 1
- Organ transplantation 1
- Close proximity to VRE-colonized patients 1
Important Caveats About Piperacillin-Tazobactam and VRE
Piperacillin-tazobactam may actually promote VRE colonization:
- Research demonstrates that piperacillin-tazobactam does not prevent VRE acquisition in ICU patients, with 26.4% of patients acquiring VRE during therapy 4
- While animal models suggested piperacillin-tazobactam might inhibit VRE colonization due to its antienterococcal activity, human studies show it may be associated with increased VRE rates in some hospitals 5, 6
- One study found VRE acquisition occurred in 6.4% of patients treated with ertapenem versus only 1.6% with piperacillin-tazobactam, though this difference was not statistically significant 7
Treatment Algorithm for Enterococcal Infections
For vancomycin-susceptible enterococci:
- Ampicillin or amoxicillin (if susceptibility confirmed) 1, 2, 3
- Piperacillin-tazobactam (if susceptibility confirmed) 1
- Vancomycin (alternative for beta-lactam intolerant patients) 1
For VRE (vancomycin-resistant):
- First-line: Linezolid 600mg IV/PO every 12 hours for monomicrobial infections 1, 2
- Alternative: Tigecycline for polymicrobial infections 1
- Salvage therapy: Daptomycin 6-12mg/kg IV daily for severe or refractory cases 2, 3
Common Pitfalls to Avoid
- Do not use fluoroquinolones for enterococcal infections due to high resistance rates 2
- Do not use cephalosporins alone for enterococcal infections, as enterococci are intrinsically resistant to cephalosporins 1
- Always obtain susceptibility testing before assuming piperacillin-tazobactam will be effective against any enterococcal isolate 2
- Infectious disease consultation is recommended for all enterococcal endocarditis and complicated VRE infections 1