title: Establishment of an AUC0-24Threshold for Nephrotoxicity Is a Step towards Individualized Vancomycin Dosing for Methicillin-Resistant Staphylococcus aureus Bacteremia.
abstract: Unlike vancomycin trough concentrations, data on the utility of vancomycin pharmacokinetic (PK) parameters, namely, the area under the concentration-time curve from 0 to 24 h (AUC0-24), in predicting acute kidney injury (AKI) are limited. Our aim was to investigate this relationship in patients receiving vancomycin therapy for methicillin-resistantStaphylococcus aureusbacteremia (MRSA-B). A single-center retrospective observational cohort study involving 127 consecutive MRSA-B patients was conducted to examine the incidence of AKI (defined as serum creatinine of ≥0.5 mg/liter and a 50% increase from baseline) and vancomycin exposure parameters associated with nephrotoxicity. Bayesian estimation was used to predict individual vancomycin AUC0-24All patients received vancomycin monotherapy for a minimum of 14 days following the diagnosis of MRSA-B. AKI was observed in 15.7% of patients (20/127). Clinical characteristics were similar between patients with and without AKI. At steady state, higher vancomycin trough concentrations were associated with AKI (17.2 mg/liter versus 13.1 mg/liter;P= 0.003). A vancomycin AUC0-24threshold for AKI of >563 mg · h/liter was detected by classification and regression tree (CART) analysis; patients with exposures above this threshold were significantly more likely to experience AKI than patients with lower vancomycin exposures (40% [8/20] versus 11.2% [12/107];P= 0.002). This parameter remained an independent predictor of AKI on multivariate logistic regression (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.57 to 16.29;P= 0.006) and was a better predictor of nephrotoxicity than vancomycin trough concentrations. Overall, AKI is associated with higher vancomycin exposure as measured by AUC0-24These results suggest that individualized patient dosing may be possible with dose modifications directed toward established pharmacodynamic targets while balancing AKI risks.
authors.affiliation: Department of Microbiology and Infectious Diseases, Gosford, NSW, Australia ruchirchavda@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Chavada
authors.affiliation: Department of Infectious Diseases and General Medicine, Wollongong and Shellharbour Hospitals, Wollongong, NSW, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology, St. Vincent's Hospital, Sydney, NSW, Australia.|University of New South Wales, Sydney, NSW, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Sandaradura
authors.affiliation: Department of Microbiology and Infectious Diseases, Liverpool, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Maley
authors.affiliation: Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Van Hal
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D003401:Creatine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003401:Creatine
keywords: AUC0–24; Bayesian estimation; MRSA; acute kidney injury; nephrotoxicity; pharmacodynamics; pharmacokinetic; trough concentrations; vancomycin