SLR - April 2021 - Jennifer Levi

Comparison of Acute Kidney Injury in Patients Prescribed Vancomycin in Combination with Piperacillin–Tazobactam or Cefepime for Diabetic Foot Infections

Reference: Piccuirro SR, Casapao AM, Claudio AM, Isache C, Jankowski CA. Comparison of Acute Kidney Injury in Patients Prescribed Vancomycin in Combination with Piperacillin–Tazobactam or Cefepime for Diabetic Foot Infections. J Investig Med. 2021 Jan 25; jim-2020-001594. doi: 10.1136/jim-2020-001594. 

Level of Evidence: Level III

Scientific Literature Review

Reviewed By: Jennifer Levi, DPM
Residency Program: Temple University Hospital – Philadelphia, PA

Podiatric Relevance: This article aims to compare drug induced acute kidney injury (AKI) comparing two empiric antibiotic regimens: vancomycin (VAN) and piperacillin-tazobactam (PTZ) vs. vancomycin (VAN) and cefepime (CFP) in a specific patient population, those with diabetic foot infections. This patient population has some of the highest baseline risk of developing an AKI given pathophysiological changes that occur in the tubular system of the diabetic kidney. Diabetic foot infections comprise a significant part of podiatric practice in both inpatient and outpatient management and often times decisions need to be made in regards to empiric coverage without any culture data. This decision is often institution or habit driven. This article may provide some evidence-based guidance when selecting a drug combination for empiric coverage in the management of diabetic foot infections. 

Methods: This was an observational, retrospective, cohort study conducted between 2012 and 2019. It looked at adult inpatients with diabetic foot infections who received VAN+PTZ or VAN+CFP initiated within 24 hours of each other, were treated with the combination for at least 48 hours, and had at least one vancomycin serum concentration analyzed for inclusion. Patients were excluded if they were diagnosed with febrile neutropenia, received >24 hours of PTZ or CFP before switching to the other agent, if they were pregnant, incarcerated, taking investigational medication, or had a documented history of CKD ≥ stage IV. The primary outcome was incidence of AKI between the two groups using the AKIN classification system to define an AKI.

Results: A total of 210 patients met the inclusion criteria for the study, of which 140 were in the VAN+PTZ group and 70 in the VAN+CFP group. Forty-nine of the 140 (35%) patients in the VAN+PTZ group developed an AKI compared to 5 of 70 (7 percent) in the VAN+CFP group. The results showed there was a significant increase in probability of developing an AKI in the VAN+PTZ group in comparison to the VAN+CFP group. There was also a statistically significant difference in median time to developing an AKI at 102.1 hours and 78.3 hours respectively, and both the median length of stay and overall total hospital charges were higher for patients in the VAN+PTZ group. Finally, after adjusting for differences in CCI, antibiotics within 90 days, and the receipt of nephrotoxic agents, VAN+PTZ was defined as an independent predictor of AKI.

Conclusions: Drug-induced nephrotoxicity has been attributed to the use of VAN+PTZ, but there has not been a great deal of research looking specifically at patients being treated for diabetic foot infections. This study was somewhat limited in that it was obtained from the EMR in an unblinded manner. It also relied on serum creatinine to assess for AKI which may be influenced by extra-renal factors and change in creatinine is delayed in relation to actual injury. Even given these limitations, this study demonstrated that a combination of cefepime and vancomycin is an alternative regimen with potentially fewer renal side effects.

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