1. Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study.
- Author
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Miano TA, Hennessy S, Yang W, Dunn TG, Weisman AR, Oniyide O, Agyekum RS, Turner AP, Ittner CAG, Anderson BJ, Wilson FP, Townsend R, Reilly JP, Giannini HM, Cosgriff CV, Jones TK, Meyer NJ, and Shashaty MGS
- Subjects
- Adult, Biomarkers, Cefepime adverse effects, Creatinine blood, Critical Illness therapy, Cystatin C blood, Drug Therapy, Combination, Humans, Penicillanic Acid adverse effects, Prospective Studies, Renal Dialysis, Retrospective Studies, Acute Kidney Injury chemically induced, Acute Kidney Injury epidemiology, Anti-Bacterial Agents adverse effects, Piperacillin, Tazobactam Drug Combination adverse effects, Vancomycin adverse effects
- Abstract
Purpose: Although dozens of studies have associated vancomycin + piperacillin-tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion., Methods: We included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin-tazobactam or vancomycin + cefepime. Kidney function biomarkers [creatinine, cystatin C, and blood urea nitrogen (BUN)] were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates., Results: The study included 739 patients (vancomycin + piperacillin-tazobactam n = 297, vancomycin + cefepime n = 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin-tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatinine-defined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin-tazobactam was not associated with change in alternative biomarkers: cystatin C: - 5.63% (95% CI - 18.19, 8.86); BUN: - 4.51% (95% CI - 12.83, 4.59); or clinical outcomes: dialysis: RR 0.63 (95% CI 0.31, 1.29); mortality: RR 1.05 (95%CI 0.79, 1.41)., Conclusions: Vancomycin + piperacillin-tazobactam was associated with creatinine-defined AKI, but not changes in alternative kidney biomarkers, dialysis, or mortality, supporting the hypothesis that vancomycin + piperacillin-tazobactam effects on creatinine represent pseudotoxicity., (© 2022. The Author(s).)
- Published
- 2022
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