Is Zosyn (piperacillin/tazobactam) effective against Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria?

Effectiveness of Zosyn Against ESBL-Producing Bacteria

Zosyn (piperacillin/tazobactam) should not be used as first-line therapy for infections caused by ESBL-producing bacteria, particularly for serious infections, as carbapenems remain the preferred treatment option. 1, 2

Current Recommendations for ESBL Infections

First-Line Treatment

• Carbapenems (meropenem, imipenem) are the first-line treatment for infections caused by ESBL-producing organisms 2
• In settings with high incidence of ESBL-producing Enterobacteriaceae, extended use of cephalosporins should be discouraged due to selective pressure resulting in emergence of resistance 1

Alternative Options for ESBL Infections

• Newer agents with activity against ESBL producers include:
  • Ceftazidime-avibactam
  • Meropenem-vaborbactam
  • Cefiderocol
  • Imipenem-relebactam 2

Role of Piperacillin/Tazobactam (Zosyn)

Limited Effectiveness

• Piperacillin/tazobactam may be effective in certain limited scenarios:
  • Non-bacteremic urinary tract infections caused by susceptible ESBL-producing E. coli 3, 4
  • Mild infections with low bacterial inoculum 5
  • When the isolate has a low MIC (≤4 μg/mL) 5, 6

Infection-Specific Considerations

• Urinary Tract Infections: Some evidence supports Zosyn use for non-bacteremic UTIs caused by susceptible ESBL-producing organisms 3, 4
• Intra-abdominal Infections: Lower success rates (70%) compared to UTIs (100%) 5
• Soft Tissue Infections: Moderate success rates (80%) 5
• Bacteremia: Not recommended based on available evidence

Important Caveats and Considerations

Optimizing Administration if Used

• If Zosyn is used for susceptible ESBL infections:
  • Extended infusion (4 hours) or continuous infusion is preferred over standard infusion 6
  • Higher dosing (4.5g four times daily) may be necessary 6
  • Only prolonged and continuous infusions achieved >90% probability of reaching 50% free time above MIC 6

Risk Factors for Treatment Failure

• High bacterial inoculum infections
• Uncontrolled source of infection
• Severe infections or sepsis
• Higher MICs (>8 μg/ml) 5
• Certain ESBL types (particularly CTX-M-15) 5

Antimicrobial Stewardship Considerations

• Inappropriate initial therapy is associated with increased mortality in ESBL infections 2
• Carbapenem-sparing strategies are important to reduce selection pressure for carbapenem-resistant organisms 7, 4
• Some studies suggest Zosyn use may be associated with lower incidence of carbapenem-resistant organisms compared to carbapenem therapy 4

Clinical Decision Algorithm

1. Assess infection severity and site:

   • Severe infection or bacteremia → Use carbapenem
   • Non-severe, non-bacteremic infection → Consider Zosyn if susceptible

2. Check susceptibility testing:

   • If MIC ≤4 μg/mL → Zosyn may be considered
   • If MIC >8 μg/mL → Use carbapenem or alternative agent

3. Consider infection site:

   • UTI without bacteremia → Zosyn may be effective if susceptible
   • Intra-abdominal or other deep-seated infections → Prefer carbapenem

4. Administration method if Zosyn selected:

   • Use extended or continuous infusion
   • Consider higher dosing (4.5g q6h)

5. Monitor closely for clinical response:

   • If inadequate response within 48-72 hours → Switch to carbapenem

In conclusion, while Zosyn may have a role in treating certain non-severe infections caused by susceptible ESBL-producing organisms, carbapenems remain the preferred treatment for serious ESBL infections to ensure optimal clinical outcomes.