SLR - September 2018 - John Boyd

Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis

Reference: Luther MK, Timbrook TT, Caffrey AR, Dosa, Lodise TP, LaPlante KL.Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis. Crit Care Med. 2018 Jan;46(1):12–20.

Scientific Literature Review

Reviewed By: John Boyd, DPM
Residency Program: St. Vincent Charity Medical Center, Cleveland, OH

Podiatric Relevance: The combination of Vancomycin and Piperacillin-Tazobactam (Zosyn) is one of the most commonly used combinations of empiric antimicrobials. Moreover, it is the firstline choice for empiric antibiotic therapy in the face of suspected diabetic foot infection for many professionals in the podiatric medical community. Recent literature has shown that AKI in patients on this therapy is caused by Zosyn, not Vancomycin as previously thought. It is important for the podiatric physician to explore other possible antimicrobial combinations for empiric therapy in the setting of the infected diabetic foot.  

Methods: This is a systematic review and metanalysis with a keyword literature search on multiple databases. Inclusive criteria included adult patients (≥18 yr old), antibiotics used (Vancomycin/Zosyn in combination and independent of one another or Vancomycin plus another beta-lactam) and extractable AKI rates. Only high-quality reports were included (Newcastle-Ottawa score ≥7). The percentage of patients developing AKI as well as time to AKI per drug regimen were extracted from the included records.

Results: Of the 3,211 unique identified records, 15 studies and 17 abstracts were included. This study noted the variance of factors between studies, including mean age (48 to 74), severity of illness, exclusion criteria (Serum Cr range 1.2 mg/dL to 2.5 mg/dL), duration of antibiosis and control of confounding factors (DM, infection type, concomitant medications).

Twenty-two percent (2,212/9,945) of patients on Vancomycin plus Zosyn developed AKI compared to 12.9 percent (1,921/14,854) of patients exposed to either vancomycin monotherapy (8.1 percent), vancomycin plus cefepime or carbapenem (20.0 percent) or Zosyn monotherapy (10.5 percent). Time to AKI was found to be slightly shorter for the Vancomycin/Zosyn group, but this was found to be statistically insignificant. The odds ratio for AKI in Vancomycin/Zosyn was found to be 2.68 versus Vancomycin plus Cefepime or Carbapenem. The number needed to harm for Vancomycin plus Zosyn therapy was 11.

A subanalysis of studies dealing with the critically ill found an odds ratio of 9.62 when comparing Vancomycin/Zosyn versus Vancomycin alone. Vancomycin/Zosyn versus Vancomycin plus Cefepime or Carbapenem was found to be insignificant in this cohort.

Conclusions: This systemic review and meta-analysis demonstrated increased odds of AKI with contaminant Vancomycin and Zosyn use. Also demonstrated in this study was a number needed to harm of 11. The incidence of AKI, though reversible, can lead to increased mortality in critically ill patients. Along with patient harm, there is the factor of increased costs associated with a longer hospital stay. Although lower, the rate of AKI in the combination therapy Vancomycin plus Cefepime or Carbepenem was significant (20 percent) showing that this alternative therapy is not the solution. Antibiotic stewardship and use of alternative antibiotics when appropriate can help decrease Vancomysin/Zosyn-related AKI. Rapid and accurate culture and sensitivity of the diabetic foot infection can arguably play the most important role in reducing risk of empiric antibiotic-related AKI with deescalation to more focused antimicrobial therapy. The mechanism of increased AKI in Vancomycin plus Zosyn is not known.

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