A Stewardship Program's Retrospective Evaluation of Vancomycin AUC24/MIC and Time to Microbiological Clearance in Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia and Osteomyelitis

Background: Current guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia recommend targeting a vancomycin AUC(24)/MIC >= 400. Data on the association between AUC(24)/MIC and microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis are limited. Objective: The objective of this study is to evaluate the association between the vancomycin AUC(24)/MIC and time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis. Methods: Adult inpatients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin from January 1, 2007, through December 31, 2011, were evaluated. Classification and regression tree analysis was used to identify the AUC(24)/MIC associated with time to microbiological clearance. Results: Fifty-nine patients had complete data available for review and were included in the analysis. Classification and regression tree analysis identified an AUC/MIC of 293 as the breakpoint that provides the greatest difference in time to microbiological clearance. On univariate analysis, mean (SD) time to clearance was 2 days shorter when the AUC/MIC was >293 (4 [2] days vs 6 [3] days, P = 0.01). Mean (SD) infection-related length of stay was 13 (6) versus 18 (14) days in patients with an AUC(24)/MIC ratio >293 or <= 293, respectively (P = 0.25). In patients with an AUC(24)/MIC <= 293, 39% versus 17% (P = 0.09) had recurrent bacteremia and were readmitted compared with patients with an AUC/MIC >293. Only 9% were able to achieve an AUC(24)/MIC >293 when the vancomycin MIC was >1 mu g/mL. Conclusions: We observed a >2.5-fold increase in time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis unable to achieve a vancomycin AUC(24)/MIC >293. A 5-day increase in hospital and infection-related length of stay was observed when this target was not achieved. Recurrence of bacteremia and hospital readmissions were higher in the cohort who did not achieve an AUC(24)/MIC >293. Only 9% of patients were able to achieve an AUC(24)/MIC >293 if the isolate MIC was >1 mu g/mL. Trough concentration did not correlate with AUC(24)/MIC. In patients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin, stewardship programs should optimize pharmacodynamic parameters, specifically AUC(24)/MIC, or alternative therapies should be considered. (C) 2013 Elsevier HS Journals, Inc. All rights reserved.