Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: A retrospective cohort analysis

W Cliff Rutter, Donna R Burgess, Jeffery C Talbert, David S Burgess, W Cliff Rutter, Donna R Burgess, Jeffery C Talbert, David S Burgess

Abstract

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

Figures

FIG
FIG
Unadjusted incidence of acute kidney injury.

References

    1. van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57:734–744.
    1. Hanrahan TP, Harlow G, Hutchinson J, et al. Vancomycin-associated nephrotoxicity in the critically ill: a retrospective multivariate regression analysis. Crit Care Med. 2014;42:2527–2536.
    1. Meaney CJ, Hynicka LM, Tsoukleris MG. Vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors. Pharmacotherapy. 2014;34:653–661.
    1. Burgess LD, Drew RH. Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. Pharmacotherapy. 2014;34:670–676.
    1. Moenster RP, Linneman TW, Finnegan PM, Hand S, Thomas Z, McDonald JR. Acute renal failure associated with vancomycin and β-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime. Clin Microbiol Infect. 2014;20:O384–O389.
    1. Gomes DM, Smotherman C, Birch A, et al. Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime. Pharmacotherapy. 2014;34:662–669.
    1. Kim T, Kandiah S, Patel M, et al. Risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy. BMC Res Notes. 2015;8:579.
    1. Davies SW, Efird JT, Guidry CA, et al. Top guns: the “Maverick” and “Goose” of empiric therapy. Surg Infect (Larchmt) 2016;17:38–47.
    1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–R212.
    1. Wilhelm SM, Kale-Pradhan PB. Estimating creatinine clearance: a meta-analysis. Pharmacotherapy. 2011;31:658–664.
    1. Paul P, Pennell ML, Lemeshow S. Standardizing the power of the Hosmer-Lemeshow goodness of fit test in large data sets. Stat Med. 2013;32:67–80.
    1. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing; Vienna, Austria: 2014. Available at:
    1. Hellwig T, Hammerquist R, Loecker B, Shields J. Retrospective evaluation of the incidence of vancomycin and/or piperacillin-tazobactam induced acute renal failure. Crit Care Med; Abstracts of the Society of Critical Care Medicine 41st Critical Care Congress; February 4–8, 2012; Houston, Texas. 2011. pp. 1–264.

Source: PubMed

3
Abonnere