title: Association between vancomycin day 1 exposure profile and outcomes among patients with methicillin-resistant Staphylococcus aureus infective endocarditis.
abstract: Given the critical importance of early appropriate therapy, a retrospective cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under the concentration-time curve (AUC0-24) and the minimum concentration at 24 h (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5, an approach shown to accurately predict the vancomycin exposure with low bias and high precision with limited pharmacokinetic sampling. Initial MRSA isolates were collected and vancomycin MIC was determined by broth microdilution (BMD) and Etest. The primary outcome was failure, defined as persistent bacteremia (≥7 days) or 30-day attributable mortality. Classification and regression tree analysis (CART) was used to determine the vancomycin exposure variables associated with an increased probability of failure. In total, 139 patients met study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had both left and right-sided IE. A total of 89/139 (64%) experienced failure by composite definition. In the CART analysis, failure was more pronounced in patients with an AUC0-24/MIC as determined by BMD of ≤600 relative to those with AUC0-24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively, P = 0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of ≤600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37; P = 0.047) was independently associated with failure. Given the retrospective nature of the present study, further prospective studies are required but these data suggest that patients with an AUC0-24/MIC as determined by BMD of ≤600 present an increased risk of failure.
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Casapao
authors.affiliation: Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA Department of Pharmacy Services, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Davis
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Claeys
authors.affiliation: Cubist Pharmaceuticals, Lexington, Massachusetts, USA.
authors.forename: Ravina
authors.initials: R
authors.lastname: Kullar
authors.affiliation: Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, Michigan, USA Department of Medicine, Division of General Internal Medicine, Detroit Receiving Hospital and University Health Center, Detroit, Michigan, USA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Levine
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, Michigan, USA m.rybak@wayne.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000328:Adult; D019540:Area Under Curve; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D014640:Vancomycin