title: Effect of vancomycin minimal inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus endocarditis.
abstract: BACKGROUND
  Staphylococcus aureus endocarditis has a high mortality rate. Vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-resistant S. aureus bacteremia, and recent data point to a similar effect on methicillin-susceptible S. aureus bacteremia. We aimed to evaluate the effect of vancomycin MIC on left-sided S. aureus infective endocarditis (IE) treated with cloxacillin.
  
  
  METHODS
  We analyzed a prospectively collected cohort of patients with IE in a single tertiary-care hospital. Vancomycin, daptomycin, and cloxacillin MIC was determined by E-test. S. aureus strains were categorized as low vancomycin MIC (<1.5 µg/mL) and high vancomycin MIC (≥1.5 µg/mL). The primary endpoint was in-hospital mortality.
  
  
  RESULTS
  We analyzed 93 patients with left-sided IE treated with cloxacillin, of whom 53 (57%) had a vancomycin MIC < 1.5 µg/mL and 40 (43%) a vancomycin MIC ≥ 1.5 µg/mL. In-hospital mortality was 30% (n = 16/53) in patients with a low vancomycin MIC and 53% (n = 21/40) in those with a high vancomycin MIC (P = .03). No correlation was found between oxacillin MIC and vancomycin or daptomycin MIC. Logistic regression analysis showed that higher vancomycin MIC increased in-hospital mortality 3-fold (odds ratio, 3.1; 95% confidence interval, 1.2-8.2) after adjustment for age, year of diagnosis, septic complications, and nonseptic complicated endocarditis.
  
  
  CONCLUSIONS
  Our results indicate that vancomycin MIC could be used to identify a subgroup of patients with methicillin-susceptible S. aureus IE at risk of higher mortality. The worse outcome of staphylococcal infections with a higher vancomycin MIC cannot be explained solely by suboptimal pharmacokinetics of antibiotics.
authors.affiliation: Infectious Diseases Service.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cervera
authors.affiliation: Infectious Diseases Service.
authors.forename: Ximena
authors.initials: X
authors.lastname: Castañeda
authors.affiliation: Experimental Endocarditis Research Laboratory.
authors.forename: Cristina Garcia
authors.initials: CG
authors.lastname: de la Maria
authors.affiliation: Infectious Diseases Service.
authors.forename: Ana
authors.initials: A
authors.lastname: del Rio
authors.affiliation: Infectious Diseases Service.
authors.forename: Asunción
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Pharmacy Service.
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.affiliation: Infectious Diseases Service.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Pericas
authors.affiliation: Cardiology Service.
authors.forename: Carlos
authors.initials: C
authors.lastname: Falces
authors.affiliation: Experimental Endocarditis Research Laboratory.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Armero
authors.affiliation: Microbiology Service.
authors.forename: Manel
authors.initials: M
authors.lastname: Almela
authors.affiliation: Department of Cardiovascular Surgery, Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Ninot
authors.affiliation: Cardiology Service.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pare
authors.affiliation: Department of Cardiovascular Surgery, Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mestres
authors.affiliation: Infectious Diseases Service.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Microbiology Service.
authors.forename: Francesc
authors.initials: F
authors.lastname: Marco
authors.affiliation: Infectious Diseases Service.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003023:Cloxacillin / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D015996:Survival Rate; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin; D003023:Cloxacillin
keywords: cloxacillin; left-sided endocarditis; methicillin-susceptible Staphylococcus aureus; mortality; vancomycin minimal inhibitory concentration