title: Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint?
abstract: Daptomycin has become a front-line antibiotic for multidrug-resistant Enterococcus faecium bloodstream infections (BSIs). We previously showed that E. faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the higher end of susceptibility frequently harbor mutations associated with daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting daptomycin MICs of 3-4 µg/mL treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs ≤2 µg/mL.
  
  
  
  We conducted a multicenter retrospective cohort study that included adult patients with E. faecium BSI for whom initial isolates, follow-up blood culture data, and daptomycin administration data were available. A central laboratory performed standardized daptomycin MIC testing for all isolates. The primary outcome was microbiologic failure, defined as clearance of bacteremia ≥4 days after the index blood culture. The secondary outcome was all-cause in-hospital mortality.
  
  
  
  A total of 62 patients were included. Thirty-one patients were infected with isolates that exhibited daptomycin MICs of 3-4 µg/mL. Overall, 34 patients had microbiologic failure and 25 died during hospitalization. In a multivariate logistic regression model, daptomycin MICs of 3-4 µg/mL (odds ratio [OR], 4.7 [1.37-16.12]; P = .014) and immunosuppression (OR, 5.32 [1.20-23.54]; P = .028) were significantly associated with microbiologic failure. Initial daptomycin dose of ≥8 mg/kg was not significantly associated with evaluated outcomes.
  
  
  
  Daptomycin MICs of 3-4 µg/mL in the initial E. faecium blood isolate predicted microbiological failure of daptomycin therapy, suggesting that modification in the daptomycin breakpoint for enterococci should be considered.
authors.affiliation: University of Texas Medical School at Houston.|Department of Infectious Diseases.
authors.forename: Bhavarth S
authors.initials: BS
authors.lastname: Shukla
authors.affiliation: Department of Infectious Diseases.|Genomic Medicine, M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Samuel
authors.initials: S
authors.lastname: Shelburne
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Katherine
authors.initials: K
authors.lastname: Reyes
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mini
authors.initials: M
authors.lastname: Kamboj
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: University of Texas Medical School at Houston.|Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Rincon
authors.affiliation: Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
authors.forename: Jinnethe
authors.initials: J
authors.lastname: Reyes
authors.affiliation: Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
authors.forename: Lina P
authors.initials: LP
authors.lastname: Carvajal
authors.affiliation: University of Texas Medical School at Houston.|Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
authors.forename: Diana
authors.initials: D
authors.lastname: Panesso
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville.
authors.forename: Costi D
authors.initials: CD
authors.lastname: Sifri
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan.|Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Zervos
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.affiliation: University of Texas Medical School at Houston.
authors.forename: Truc T
authors.initials: TT
authors.lastname: Tran
authors.affiliation: Department of Infectious Diseases.
authors.forename: Javier
authors.initials: J
authors.lastname: Adachi
authors.affiliation: University of Texas Medical School at Houston.|Clinica Alemana, Universidad del Desarrollo, Santiago, Chile.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Munita
authors.affiliation: University of Texas Medical School at Houston.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Hasbun
authors.affiliation: University of Texas Medical School at Houston.|Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Arias
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D017576:Daptomycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin
keywords: E. faecium; MIC; bloodstream infection; daptomycin; resistance