SLR - July 2018 - Stephen E. Dunham

Nephrotoxicity During Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime

Reference: Rutter WC, Cox JN, Martin CA, Burgess DR, Burgess DS. Nephrotoxicity During Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime. Antimicrob Agents Chemother. 2017 Jan 24;61(2).

Scientific Literature Review

Reviewed By: Stephen E. Dunham, DPM
Residency Program: HealthAlliance of the Hudson Valley, Kingston, NY

Podiatric Relevance: Vancomycin and piperacillin-tazobactam are common hospital-based empiric antibiotic therapy for diabetic foot infections. It is well known that vancomycin provides coverage for suspected methicillin-resistant staphylococcus aureus (MRSA) infections while piperacillin-tazobactam allows for non-MRSA gram positive, gram negative and pseudomonas treatment. It is also well known that nephrotoxicity must be taken into consideration when selecting an antibiotic, more notably with vancomycin alone where acute kidney injury (AKI) has been estimated as high as 42 percent. Recent studies have reported the combination of vancomycin with an antipseudomonal beta-lactam may increase the incidence of AKI. As such, an alternative combination of vancomycin with cefepime has been suggested. This retrospective study reviews the incidence of AKI associated with vancomycin and piperacillin-tazobactam (TZP-VAN) versus vancomycin and cefepime (FEP-VAN) at a single medical center over four years.

Methods: An IRB-approved, retrospective study of patients admitted to the University of Kentucky HealthCare Medical Center between September 1, 2010 and September 1, 2014 who received either TZP-VAN or FEP-VAN was performed. Vancomycin was dosed according to institutional policy with serum concentrations monitored by pharmacists and adjusted accordingly. Patient selection consisted of those 18 years of age or older with antibiotic treatment of a minimum of 48 hours. Excluded were those with history of chronic kidney disease stage 3 or higher, structural kidney disease, on dialysis, prior AKI, had underlying renal dysfunction (CC < 30), were pregnant, diagnosed with cystic fibrosis or were hospital transfers on either antibiotic combination within previous 48 hours. Data collected included demographics, length of stay, admitting and primary diagnosis, serum creatinine levels and receipt of other nephrotoxic or IV contrast agents. After 10,141 patients were screened, 1,633 patients were matched to the TZP-VAN group, and 578 were matched to the FEP-VAN group.

Results: AKI was more common in the TZP-VAN group with 21.4 percent of patients versus 12.5 percent in the VAN-FEP group, P < 0.0001. All levels of the risk, injury, failure, loss of kidney function and end-stage kidney disease criteria were more common in the TZP-VAN group versus the VAN-FEP group. Regression analysis showed TZP-VAN associated with 2.18 times the odds of AKI versus FEP-VAN (95 percent CI, 1.64 to 2.94). Median time to AKI in days for TZP-VAN group was five (three to nine) versus FEP-VAN group, which was eight (five to 14) P < 0.0004. No statistical difference was noted with length of stay (average eight days for both).

Conclusion: A significant difference was found in favor of FEP-VAN versus TZP-VAN in the reduction of antibiotic-induced AKI. This large retrospective study aimed to rectify the small sample size of previous studies regarding this antibiotic comparison. AKI incidence is multifactorial. Although this study attempts to standardize patient selection, this presents itself as a limitation to the study. Also, causality can be challenging to prove in a retrospective study. Regardless, results of this study warrant further consideration regarding vancomycin and cefepime as a safer alternative to vancomycin and piperacillin-tazobactam for empiric DFU coverage in reduction of nephrotoxicity. 

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