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- Title
Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study.
- Authors
Miano, Todd A.; Hennessy, Sean; Yang, Wei; Dunn, Thomas G.; Weisman, Ariel R.; Oniyide, Oluwatosin; Agyekum, Roseline S.; Turner, Alexandra P.; Ittner, Caroline A. G.; Anderson, Brian J.; Wilson, F. Perry; Townsend, Raymond; Reilly, John P.; Giannini, Heather M.; Cosgriff, Christopher V.; Jones, Tiffanie K.; Meyer, Nuala J.; Shashaty, Michael G. S.
- Abstract
<bold>Purpose: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
CYSTATIN C; VANCOMYCIN; CRITICALLY ill; BLOOD urea nitrogen; ACUTE kidney failure; PROTEINS; COMBINATION drug therapy; RETROSPECTIVE studies; CATASTROPHIC illness; PENICILLIN; AMPICILLIN; RESEARCH funding; HEMODIALYSIS; CREATININE; ANTIBIOTICS; LONGITUDINAL method
- Publication
Intensive Care Medicine, 2022, Vol 48, Issue 9, p1144
- ISSN
0342-4642
- Publication type
journal article
- DOI
10.1007/s00134-022-06811-0