title: Resistance to empiric antimicrobial treatment predicts outcome in severe sepsis associated with Gram-negative bacteremia.
abstract: BACKGROUND
  Gram-negative bacteria are an important cause of severe sepsis. Recent studies have demonstrated reduced susceptibility of Gram-negative bacteria to currently available antimicrobial agents.
  
  
  METHODS
  We performed a retrospective cohort study of patients with severe sepsis who were bacteremic with Pseudomonas aeruginosa, Acinetobacter species, or Enterobacteriaceae from 2002 to 2007. Patients were identified by the hospital informatics database and pertinent clinical data (demographics, baseline severity of illness, source of bacteremia, and therapy) were retrieved from electronic medical records. All patients were treated with antimicrobial agents within 12 hours of having blood cultures drawn that were subsequently positive for bacterial pathogens. The primary outcome was hospital mortality.
  
  
  RESULTS
  A total of 535 patients with severe sepsis and Gram-negative bacteremia were identified. Hospital mortality was 43.6%, and 82 (15.3%) patients were treated with an antimicrobial regimen to which the causative pathogen was resistant. Patients infected with a resistant pathogen had significantly greater risk of hospital mortality (63.4% vs 40.0%; P < 0.001). In a multivariate analysis, infection with a pathogen that was resistant to the empiric antibiotic regimen, increasing APACHE II scores, infection with Pseudomonas aeruginosa, healthcare-associated hospital-onset infection, mechanical ventilation, and use of vasopressors were independently associated with hospital mortality.
  
  
  CONCLUSIONS
  In severe sepsis attributed to Gram-negative bacteremia, initial treatment with an antibiotic regimen to which the causative pathogen is resistant was associated with increased hospital mortality. This finding suggests that rapid determination of bacterial susceptibility could influence treatment choices in patients with severe sepsis potentially improving their clinical outcomes.
authors.affiliation: Pharmacy Department, Barnes-Jewish Hospital, St. Louis, Missouri, USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Micek
authors.forename: Emily C
authors.initials: EC
authors.lastname: Welch
authors.forename: Junaid
authors.initials: J
authors.lastname: Khan
authors.forename: Mubashir
authors.initials: M
authors.lastname: Pervez
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Doherty
authors.forename: Richard M
authors.initials: RM
authors.lastname: Reichley
authors.forename: Joan
authors.initials: J
authors.lastname: Hoppe-Bauer
authors.forename: W Michael
authors.initials: WM
authors.lastname: Dunne
authors.forename: Marin H
authors.initials: MH
authors.lastname: Kollef
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D017052:Hospital Mortality / Q000639:trends*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents