Difference in Nephrotoxicity Between Nafcillin and Piperacillin-Tazobactam

Abstract

Background. There is evidence of an increased acute kidney injury (AKI) risk with the combination of vancomycin and piperacillin-tazobactam (TZP) compared to vancomycin and cefepime or vancomycin alone. It is unknown whether this effect is exclusive for TZP. The objective of this study was to evaluate whether nephrotoxicity differs between nafcillin (NAF) and TZP in adult hospitalized patients. Methods. A single-center, retrospective cohort study was performed utilizing electronic health records at University of Kentucky HealthCare. Adult hospitalized patients being treated with NAF or TZP from 1 September 2010 to 1 September 2014 were included in the study. Age, sex, Charlson Comorbidity Index (CCI), baseline creatinine clearance, dehydration, hypotension, exposure to concomitant nephrotoxins, and duration of therapy were evaluated. The primary outcome was AKI as defined by the RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage kidney disease) and evaluated using multivariable logistic regression. Secondary outcomes included time to AKI from initiation of antibiotics, hospital length of stay, and mortality. Results. Of the 3393 patients included in this study, 272 were treated with NAF and 3121 were treated with TZP. The mean age was 52.82 +/- 17.48 years with 1709 (50.37%) males. Mean CCI and baseline creatinine clearance were 3.42 +/- 3.62 and 100.91 +/- 42.89 mL/min, respectively. Overall AKI incidence was 19.49% in the NAF group and 7.72% in the TZP group (p < 0.0001). After adjusting for confounders, those in the NAF group had 2.00 (95% CI 1.36-2.95) times the odds of AKI compared to those in the TZP group. Time to AKI was 6.00 +/- 5.14 days in the NAF group and 4.69 +/- 3.41 days in the TZP group (p = 0.0458). Hospital length of stay was 14.38 +/- 12.69 days in the NAF group and 7.44 +/- 7.55 days in the TZP group (p < 0.0001). Inpatient mortality occurred in 23 patients (8.46%) in the NAF group and 112 (3.59%) in the TZP group (p < 0.0001). Conclusion. This study suggests that NAF has a significantly greater potential for nephrotoxicity compared to TZP. Future research may involve further evaluating the risk factors of AKI, indication, and dosing schedule of these or other antibiotics in a larger population.