title: The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels.
abstract: BACKGROUND
  This study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock.
  
  
  METHODS
  Surgical implantation of an E. coli (O18:K1:H7)-laced, gelatin capsule-encased fibrinogen clot was used to generate a bacteremic model of murine septic shock. Survival duration, hemodynamic responses, and circulating serum tumor necrosis factor (TNF)-alpha , interleukin (IL)-6, and lactate levels were assessed in relation to increasing delays in or absence of antibiotic treatment.
  
  
  RESULTS
  A critical inflection point with respect to survival occurred between 12 and 15 h after implantation. When initiated at or before 12 h, antibiotic treatment resulted in < or = 20% mortality, but, when initiated at or after 15 h, it resulted in >85% mortality. Physiologically relevant hypotension developed in untreated septic mice by 12 h after implantation. Values for heart rate differed between untreated septic mice and sham-infected control mice by 6 h after implantation, whereas values for cardiac output and stroke volume did not differ until at least 18-24 h after implantation. Antibiotic treatment initiated > or = 12 h after implantation was associated with persistence of increased circulating serum lactate, TNF- alpha , and IL-6 levels.
  
  
  CONCLUSIONS
  The timing of antibiotic treatment relative to hypotension is closely associated with survival in this murine model of septic shock. Delay in antibiotic treatment results in the persistence of inflammatory/stress markers even after antibiotic treatment is initiated.
authors.affiliation: Division of Cardiovascular Diseases and Critical Care Medicine, Cooper Hospital/University Medical Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden, New Jersey. akumar61@yahoo.com
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Cameron
authors.initials: C
authors.lastname: Haery
authors.forename: Bhanu
authors.initials: B
authors.lastname: Paladugu
authors.forename: Aseem
authors.initials: A
authors.lastname: Kumar
authors.forename: Simon
authors.initials: S
authors.lastname: Symeoneides
authors.forename: Leo
authors.initials: L
authors.lastname: Taiberg
authors.forename: Jailan
authors.initials: J
authors.lastname: Osman
authors.forename: Gordon
authors.initials: G
authors.lastname: Trenholme
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.forename: Roy
authors.initials: R
authors.lastname: Goldfarb
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parrillo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002302:Cardiac Output; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate; D007022:Hypotension / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D051379:Mice; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D013223:Statistics as Topic; D013318:Stroke Volume; D016019:Survival Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid