Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: A retrospective cohort analysis
Background
Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.
Objective
This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.
Design, Setting, and Patients
This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.
Measurements
The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria.
Methods
Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.
Results
Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. 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 (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI],1.74-2.39; aOR, 2.31; 95% CI, 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.
Conclusions
In this study of more than 10,000 patients, 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. Journal of Hospital Medicine 2017;12:77-82. © 2017 Society of Hospital Medicine
© 2017 Society of Hospital Medicine
Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Literature from a variety of patient populations reports nephrotoxicity associated with VAN, targeting troughs greater than 15 µg/mL, that occur in 5% to 43% of patients.1 In a study of critically ill patients, acute kidney injury (AKI) was found in 21% of patients receiving VAN, with increasing duration of VAN treatment, greater VAN levels, concomitant vasoactive medication administration, and intermittent infusion methods being associated with higher odds of AKI.2 A recent report from adult internal medicine patients estimated the incidence of VAN-associated nephrotoxicity at 13.6% and implicated concomitant PTZ therapy as a key factor in these patients.3
Further studies have explored the interaction between empiric beta-lactam and VAN therapy, showing mixed results. Reports of AKI associated with the combination of VAN and PTZ range from 16.3% to 34.8%,4-8 while the cefepime-VAN combination is reported to range from 12.5% to 13.3%.5,6 While VAN monotherapy groups were well represented, only 1 study7 compared the PTZ-VAN combination to a control group of PTZ monotherapy.
The primary objective of this study was to evaluate the differences in AKI incidence between patients treated with VAN and with PTZ, alone and in combination.
METHODS
This is a retrospective cohort study of adult patients conducted at the University of Kentucky Chandler Medical Center (UKMC) from September 1, 2010 through August 31, 2014. Patients were included if they were at least 18 years of age on admission; remained hospitalized for at least 48 hours; received VAN combined with PTZ (VAN/PTZ), VAN alone, or PTZ alone; and had at least 48 hours of therapy (and 48 hours of overlapping therapy in the VAN/PTZ group). Patients were excluded if they had underlying diagnosis of chronic kidney disease according to the International Classification of Diseases 9 (ICD-9) code, were receiving renal replacement therapy before admission, had a diagnosis of cystic fibrosis, or were pregnant. Additionally, patients were excluded if they presented with AKI, defined as an initial creatinine clearance less than 30 mL/min, or if baseline creatinine clearance was greater than 4 times the standard deviation from the mean; serum creatinine values were not obtained during admission; and if AKI occurred prior to therapy initiation, within 48 hours of initiation, or more than 7 days after treatment was discontinued. Patients were followed throughout their stay until time of discharge.
