title: Evaluation of vancomycin population susceptibility analysis profile as a predictor of outcomes for patients with infective endocarditis due to methicillin-resistant Staphylococcus aureus.
abstract: Infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA IE) is associated with high morbidity and mortality. Vancomycin continues to be the primary treatment for this disease. The emergence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), defined as a modified population analysis profile (PAP) of ≥ 0.9, may affect patient outcomes. The objective of this study was to evaluate the relationship of vancomycin subpopulation susceptibility and the clinical outcomes of MRSA IE. We conducted a retrospective cohort study of patients treated with vancomycin for MRSA IE from 2002 to 2013 at the Detroit Medical Center. A modified PAP was used to measure the vancomycin PAP MIC and the PAP-to-area under the curve (AUC) ratio. Treatment failure was defined as bacteremia for ≥ 7 days or death attributed to MRSA. Classification and regression tree (CART) analysis was used to select a failure breakpoint between the PAP-AUC ratios and the PAP MIC. A total of 202 patients were included in the study. Twenty-seven percent of the patients had left-sided IE, 19% of the strains were hVISA, and 70% of the strains were staphylococcal cassette chromosome mec element (SCCmec) type IV. Overall treatment failure was observed in 64%; 59% had persistent bacteremia, and the 30-day attributable mortality rate was 21%. The CART breakpoint between failure and success in terms of the PAP-AUC ratio was 0.9035. On logistic regression analysis, intensive care unit (ICU) admission (adjusted odds ratio [aOR], 2.8; 95% confidence interval [CI], 1.5 to 5.2) and a PAP MIC of ≥ 4 mg/liter (aOR, 3.2; 95% CI, 1.3 to 8.4) were associated with failure (P = 0.001 and 0.015, respectively). A PAP MIC of ≥ 4 mg/liter and ICU admission were significant for treatment failure for patients with MRSA IE. The PAP-AUC ratio of ≥ 0.9035 predicted failure consistent with the hVISA definition. The role of population MIC analysis in predicting outcome with MRSA infections warrants further investigation.
authors.affiliation: Anti-Infective Research Laboratory, 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: Anti-Infective Research Laboratory, 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, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: John Paul
authors.initials: JP
authors.lastname: McRoberts
authors.affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Abdalhamid M
authors.initials: AM
authors.lastname: Lagnf
authors.affiliation: Pharmacy Department, Georgia Regents Health System, Augusta, Georgia, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Patel
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.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Levine
authors.affiliation: Anti-Infective Research Laboratory, 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 Detroit Receiving Hospital and University Health Center, Detroit, Michigan, USA m.rybak@wayne.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D024881:Drug Resistance, Bacterial; D004696:Endocarditis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008712:Methicillin / Q000627:therapeutic use; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D008712:Methicillin