For a patient with Acute Kidney Injury (AKI), should I use vancomycin plus cefepime or vancomycin plus Zosyn (piperacillin/tazobactam)?

Vancomycin Plus Cefepime is Preferred Over Vancomycin Plus Zosyn in Patients with AKI

For patients with Acute Kidney Injury (AKI), vancomycin plus cefepime is strongly recommended over vancomycin plus piperacillin-tazobactam (Zosyn) due to significantly lower risk of worsening kidney injury. 1, 2, 3

Evidence for Increased AKI Risk with Vancomycin Plus Zosyn

• Multiple studies consistently demonstrate that the combination of vancomycin with piperacillin-tazobactam significantly increases the risk of AKI compared to vancomycin with cefepime or other beta-lactams 3, 4
• A 2022 systematic review and meta-analysis found that vancomycin plus Zosyn was associated with a 79% higher risk ratio of AKI compared to alternative combinations (RR 1.79; 95% CI, 1.46-2.19) 2
• When specifically comparing vancomycin plus Zosyn to vancomycin plus cefepime, the risk ratio for AKI was 1.70 (95% CI, 1.36-2.12) 2
• A 2022 retrospective cohort study using area under the curve (AUC)-based vancomycin dosing still found significantly higher AKI incidence with vancomycin plus piperacillin-tazobactam compared to vancomycin plus meropenem or cefepime (13.6% vs 4.8%, p=0.014) 1

Specific Recommendations for AKI Patients

• In patients with AKI, each additional nephrotoxin administration presents 53% greater odds of developing or worsening kidney injury 5
• Selecting a less nephrotoxic antibiotic combination is strongly recommended in patients with AKI 6
• Vancomycin should be avoided in patients with AKI unless no suitable, less nephrotoxic therapeutic alternatives are available 6
• When broad-spectrum coverage is needed in critically ill patients, cefepime plus metronidazole is recommended as an alternative to piperacillin-tazobactam 5

Mechanism and Risk Factors

• The exact mechanism for increased nephrotoxicity with vancomycin plus piperacillin-tazobactam remains unclear, but appears to be a pharmacodynamic interaction 3
• Risk factors that further increase AKI risk include:
  • Vancomycin trough levels >20 mg/L 7
  • Baseline renal dysfunction 7
  • Vasopressor use 7
  • Longer duration of combination therapy 7

Monitoring and Management Considerations

• If vancomycin is necessary in a patient with AKI:
  • Adjust dosing based on renal function 5
  • Implement more frequent monitoring of vancomycin levels and renal function 6
  • Consider therapeutic drug monitoring when treatment extends beyond 48 hours 6
  • Minimize the duration of therapy when possible 5

Clinical Decision Algorithm

1. For empiric coverage requiring gram-positive plus gram-negative coverage in a patient with AKI:

   • First choice: Vancomycin plus cefepime 2, 3
   • Second choice: Vancomycin plus meropenem (if broader coverage needed) 2
   • Avoid: Vancomycin plus piperacillin-tazobactam 1, 4

2. If the patient requires anaerobic coverage:

   • Add metronidazole to vancomycin plus cefepime regimen 5

3. For patients with severe infections requiring broad-spectrum coverage:

   • Consider carbapenem-based regimens as specified in guidelines for critically ill patients 5

Common Pitfalls to Avoid

• Continuing vancomycin plus piperacillin-tazobactam in patients who develop worsening renal function 6
• Failing to adjust dosing based on changing renal function 5
• Combining multiple nephrotoxic agents, which compounds AKI risk 5
• Using trough-based rather than AUC-based vancomycin dosing, which may increase nephrotoxicity 1