title: Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.
abstract: OBJECTIVE
  Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation.
  
  
  METHODS
  This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance.
  
  
  RESULTS
  A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P < 0.01) and ICU stay (odds ratio, 2.64; P = 0.03). Notable differences between treatment groups were seen with: (1) end of therapy failure rates (11% vs 24% for daptomycin vs vancomycin; P = 0.025); (2) acute kidney injury rates (9% vs 23% for daptomycin vs vancomycin; P = 0.043); and (3) day 4 bacteremia clearance rates for immunocompromised patients (n = 26) (94% vs 56% for daptomycin vs vancomycin; P = 0.035).
  
  
  CONCLUSIONS
  Results from this multicenter study provide, for the first time, a geographically diverse evaluation of daptomycin versus vancomycin for patients with vancomycin-susceptible MRSA bacteremia with vancomycin MIC values >1 µg/mL. Although the overall composite failure rates did not differ between the vancomycin and daptomycin groups when intensively matched according to risks for failure, the rates of acute kidney injury were significantly lower in the daptomycin group. These findings suggest that daptomycin is a useful therapy for clinicians treating patients who have MRSA bacteremia. Prospective, randomized trials should be conducted to better assess the potential significance of elevated vancomycin MIC.
authors.affiliation: Department of Medical Affairs, Merck & Co Inc, Kenilworth, New Jersey. Electronic address: pamela.moise@merck.com.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Moise
authors.affiliation: Department of Medical Affairs, Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Darren L
authors.initials: DL
authors.lastname: Culshaw
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Economics & Policy, University of Southern California, Los Angeles, California.
authors.forename: Annie
authors.initials: A
authors.lastname: Wong-Beringer
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Economics & Policy, University of Southern California, Los Angeles, California.
authors.forename: Joyce
authors.initials: J
authors.lastname: Bensman
authors.affiliation: Department of Medical Affairs, Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Lamp
authors.affiliation: Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma.
authors.forename: Winter J
authors.initials: WJ
authors.lastname: Smith
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Karri
authors.initials: K
authors.lastname: Bauer
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Goff
authors.affiliation: Department of Pharmacy, St. Barnabas Health Care System, Livingston, New Jersey.
authors.forename: Robert
authors.initials: R
authors.lastname: Adamson
authors.affiliation: Department of Clinical Pharmacy, University Medical Center of Southern Nevada, Las Vegas, Nevada.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Leuthner
authors.affiliation: Division of Infectious Diseases, Yale-New Haven Hospital-SRC, New Haven, Connecticut.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Virata
authors.affiliation: Torrance Memorial Medical Center Division of Infectious Diseases & Infectious Disease Clinical Outcomes Research at LA Biomedical Research Institute, Torrance, California.
authors.forename: James A
authors.initials: JA
authors.lastname: McKinnell
authors.affiliation: Department of Pharmacy Practice and Administration, Jersey Shore University Medical Center and Rutgers University, Neptune, New Jersey.
authors.forename: Saira B
authors.initials: SB
authors.lastname: Chaudhry
authors.affiliation: Department of Pharmacy, Glendale Adventist Medical Center, Glendale, California.
authors.forename: Romic
authors.initials: R
authors.lastname: Eskandarian
authors.affiliation: Albany College of Pharmacy, Albany, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lodise
authors.affiliation: Division of Infectious Diseases, Henry Ford Hospital and Wayne State University, Detroit, Michigan.
authors.forename: Katherine
authors.initials: K
authors.lastname: Reyes
authors.affiliation: Division of Infectious Diseases, Henry Ford Hospital and Wayne State University, Detroit, Michigan.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Zervos
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D017576:Daptomycin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D057216:Propensity Score; D012008:Recurrence; D012044:Regression Analysis; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy*; D017211:Treatment Failure; D016896:Treatment Outcome; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin
keywords: MRSA bacteremia; daptomycin; high MIC; multicenter; vancomycin