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Published on: April 18, 2019
Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with
Breanne Mefford1,2, Katie L Wallace1,2, J Chris Donaldson1,2
1Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky, USA.
Abstract:
Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.
Insights
Piperacillin-tazobactam (TZP) use with vancomycin (VAN) increased acute kidney injury (AKI) risk compared to cefepime/meropenem. Vancomycin monitoring strategy (AUC vs. trough) did not alter this AKI risk. MAKE-30 outcomes were similar across groups.
Area of Science:
- Pharmacology
- Nephrology
- Critical Care Medicine
Background:
- Piperacillin-tazobactam (TZP) and vancomycin (VAN) are frequently used for sepsis.
- Studies indicate TZP and VAN increase acute kidney injury (AKI) risk compared to cefepime (FEP) or meropenem (MEM).
- Current VAN guidelines suggest area under the curve (AUC) monitoring over trough (Tr) to mitigate AKI risk.
Purpose of the Study:
- To investigate the association of AKI and 30-day multi-}}{(attribute) kidney injury (MAKE-30) with VAN monitoring strategies (AUC vs. Tr).
- To compare these outcomes when VAN is combined with TZP versus FEP/MEM.
Main Methods:
- Retrospective study of adult patients receiving VAN for >72 hours between 2015-2019.
- Exclusion criteria included pre-existing AKI or low baseline creatinine clearance (CrCl).
- Four cohorts were analyzed: FEP/MEM with Tr or AUC monitoring, and TZP with Tr or AUC monitoring. Cox Proportional Hazard Models and multivariable logistic regression were used.
Main Results:
- Overall AKI incidence was 18.6%.
- Higher AKI rates were observed in the TZP groups (26% Tr, 17.1% AUC) compared to FEP/MEM groups (14.6% Tr, 14.9% AUC).
- Both drug choice (TZP) and monitoring strategy (Tr) were significantly associated with AKI, but no interaction effect was found. MAKE-30 outcomes did not differ significantly across cohorts.
Conclusions:
- Piperacillin-tazobactam use, regardless of vancomycin monitoring strategy, is associated with a higher risk of acute kidney injury.
- Vancomycin monitoring strategy (AUC vs. trough) did not modify the risk of AKI when used with piperacillin-tazobactam.
- MAKE-30 outcomes were comparable across all treatment and monitoring strategy groups.
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