Year of Publication



Public Health

Degree Name

Master of Public Health (M.P.H.)

Committee Chair

Daniela Moga, MD, PhD

Committee Member

Craig Martin, PharmD, MBA, BCPS-AQID

Committee Member

Lorie Chesnut, DrPH, MPH

Committee Member

David Mannino, MD



To evaluate whether nephrotoxicity differs between nafcillin and piperacillin-tazobactam in adult hospitalized patients.


Acute kidney injury (AKI) is a significant cause of morbidity and mortality in the inpatient setting, with antibiotics being a significant contributor. There is evidence of an increased risk of nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam compared to vancomycin and cefepime or vancomycin alone. It is unknown whether this effect is exclusive for piperacillin-tazobactam. Therefore, in order to promote optimal medication therapy for inpatient bacterial infections, there is a need to assess the persistence of this difference in other beta-lactam antibiotics.


A single-center, retrospective cohort study was performed utilizing electronic health records at University of Kentucky Healthcare. Adult hospitalized patients being treated with nafcillin or piperacillin-tazobactam from September 1, 2010 to September 1, 2014 were included in the study. Age, sex, Charlson Comorbidity Index, 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), where risk, injury, and failure were defined as a 25%, 4 50%, and 75% decrease in glomerular filtration rate from baseline, respectively. Secondary outcomes included time to AKI from initiation of antibiotics, hospital length of stay, and mortality.


Of the 3,393 patients included in this study, 272 were treated with nafcillin and 3,121 were treated with piperacillin-tazobactam. Overall incidence of AKI was 19.49% in the nafcillin group and 7.72% in the piperacillin-tazobactam group (p<0.0001). After adjusting for age, sex, Charlson Comorbidity Index, baseline creatinine clearance, hypotension, number of concomitant nephrotoxins, and duration of therapy, those in the nafcillin group had 2.002 (95% CI 1.357- 2.953) times the odds of AKI compared to those in the piperacillin-tazobactam group. Time to AKI, hospital length of stay, and inpatient mortality were also significantly higher in the nafcillin group.


The results from this study suggest that nafcillin has a significantly greater potential for nephrotoxicity compared to piperacillin-tazobactam. Future research may involve further evaluating the risk factors of AKI, indication, and dosing schedule of these or other antibiotics in a larger population.

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