title: Early response assessment to guide management of methicillin-resistant Staphylococcus aureus bloodstream infections with vancomycin therapy.
abstract: BACKGROUND
  A subset of vancomycin-treated patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) developed persistent positive blood cultures. Treatment eventually failed.
  
  
  METHODS
  A retrospective study was conducted to determine whether early response on day 3 after initiation of vancomycin therapy for MRSA BSI was associated with reduced rates of persistent bacteremia, end-of-treatment failure, and infection-related mortality. Patients' medical charts were reviewed. Susceptibility testing and molecular characterization of bacterial isolates were performed.
  
  
  RESULTS
  In this elderly cohort (n = 111; median age 70 years, interquartile range: 57-80 years), early response was observed in 62% of patients and was significantly (P < 0.0001) associated with lower rates of end-of-treatment failure (19% vs 57%) and infection-related death (1% vs 29%), but not with persistent bacteremia (17% vs 29%, P = 0.23). Nearly half (46%; 46 of 100 patients) remained on vancomycin therapy for the entire treatment course; those who continued despite lack of early response had a trend toward a higher risk of death than those who were switched to alternative therapy (38% vs 10%, P = NS). Most (68%) isolates had vancomycin MIC of >1 µg/mL, whereas 10% showed heterogeneous glycopeptide-intermediate Staph aureus (hGISA) phenotype. Nearly half (47%) were typed with staphylococcal cassette chromosome mec IV or V. In a multivariate logistic regression model, lack of response at day 3 was the strongest predictor for end-of-treatment failure, after adjustment for confounders such as age, Acute Physiology And Chronic Health Evaluation II score, intensive care unit admission, vancomycin MIC >1 µg/mL, unbound trough concentration <4 to 5× MIC, and continued vancomycin therapy without change.
  
  
  CONCLUSIONS
  Early response assessment after initiation of vancomycin therapy appeared to be useful for considering further diagnostic workup or a switch to alternative therapy to affect a positive outcome in patients with MRSA BSI.
authors.affiliation: University of Southern California, School of Pharmacy, Los Angeles, CA, USA.
authors.forename: Julianne
authors.initials: J
authors.lastname: Joo
authors.forename: Jason
authors.initials: J
authors.lastname: Yamaki
authors.forename: Mimi
authors.initials: M
authors.lastname: Lou
authors.forename: Shenche
authors.initials: S
authors.lastname: Hshieh
authors.forename: Tony
authors.initials: T
authors.lastname: Chu
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Shriner
authors.forename: Annie
authors.initials: A
authors.lastname: Wong-Beringer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008875:Middle Aged; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013211:Staphylococcus aureus / Q000302:isolation & purification; D017211:Treatment Failure; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: MRSA; MRSA bloodstream infection; vancomycin