Year of Publication


Degree Name

Master of Science (MS)

Document Type

Master's Thesis




Pharmaceutical Sciences

First Advisor

Dr. David S. Burgess


Empiric antimicrobial therapy often consists of the combination of Gram-positive coverage with vancomycin (VAN) and Gram-negative coverage, specifically an anti-pseudomonal beta-lactam, such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports demonstrate increasing nephrotoxicity rates among patients treated with the combination of VAN and PTZ. This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI), as defined by the RIFLE criteria, compared to VAN and PTZ monotherapies.

Overall, 11,650 patients were analyzed, with 1,647 (14.1%) AKI cases occurring. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, p<0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (aOR=2.03; 95% CI 1.74-2.39; aOR=2.31; 95% CI 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs were independently associated with increased AKI rates, as were increased duration of therapy, length of hospital stay, increasing severity of illness, and increasing baseline renal function.

VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy.

Digital Object Identifier (DOI)