title: An association between bacterial genotype combined with a high-vancomycin minimum inhibitory concentration and risk of endocarditis in methicillin-resistant Staphylococcus aureus bloodstream infection.
abstract: BACKGROUND
  Antimicrobial resistance and bacterial virulence factors may increase the risk of hematogenous complications during methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). This study reports on the impact of increasing vancomycin minimum inhibitory concentrations (V-MICs) and MRSA clone type on risk of hematogenous complications from MRSA BSI during implementation of an effective MRSA control program.
  
  
  METHODS
  In sum, spa typing, staphylococcal cassette chromosome mec allotyping, and vancomycin and teicoplanin MICs were performed on 821 consecutive MRSA bloodstream isolates from 1999 to 2009. Prospectively collected data, including focus of infection, were available for 695 clinically significant cases. Logistic and multinomial logistic regression was used to determine the association between clone type, vancomycin MIC (V-MIC), and focus of infection.
  
  
  RESULTS
  MRSA BSIs decreased by ∼90% during the 11 years. Typing placed isolates into 3 clonal complex (CC) groups that had different population median V-MICs (CC30, 0.5 μg/mL [n = 349]; CC22, 0.75 μg/mL [n = 272]; non-CC22/30, 1.5 μg/mL [n = 199]). There was a progressive increase in the proportion of isolates with a V-MIC above baseline median in each clonal group and a disproportionate fall in the clone group with lowest median V-MIC (CC30). In contrast, there were no increases in teicoplanin MICs. High V-MIC CC22 isolates (1.5-2 μg/mL) were strongly associated with endocarditis (odds ratio, 12; 95% confidence interval, 3.72-38.9) and with a septic metastasis after catheter-related BSI (odds ratio, 106; 95% confidence interval, 12.6-883) compared with other clone type/V-MIC combinations.
  
  
  CONCLUSIONS
  An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.
authors.affiliation: Department of Infectious Diseases, King's College London School of Medicine, United Kingdom.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Miller
authors.forename: Rahul
authors.initials: R
authors.lastname: Batra
authors.forename: Ben S
authors.initials: BS
authors.lastname: Cooper
authors.forename: Amita K
authors.initials: AK
authors.lastname: Patel
authors.forename: John
authors.initials: J
authors.lastname: Klein
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Otter
authors.forename: Theodore
authors.initials: T
authors.lastname: Kypraios
authors.forename: Gary L
authors.initials: GL
authors.lastname: French
authors.forename: Olga
authors.initials: O
authors.lastname: Tosas
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Edgeworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000382:microbiology*; D004697:Endocarditis, Bacterial / Q000453:epidemiology* / Q000382:microbiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012306:Risk; D013203:Staphylococcal Infections / Q000382:microbiology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D014640:Vancomycin