title: Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study.
abstract: BACKGROUND
  Spontaneous bacterial peritonitis (SBP)-associated septic shock carries significant mortality in cirrhosis.
  
  
  OBJECTIVE
  To determine whether practice-related aspects of antimicrobial therapy contribute to high mortality.
  
  
  METHODS
  Retrospective cohort study of all (n = 126) cirrhotics with spontaneous bacterial peritonitis (neutrophil count >250 or positive ascitic culture)-associated septic shock (1996-2011) from an international, multicenter database. Appropriate antimicrobial therapy implied either in vitro activity against a subsequently isolated pathogen (culture positive) or empiric management consistent with broadly accepted norms (culture negative).
  
  
  RESULTS
  Overall hospital mortality was 81.8%. Comparing survivors (n = 23) with non-survivors (n = 103), survivors had lower Acute Physiology and Chronic Health Evaluation (APACHEII) (mean ± s.d.; 22 ± 7 vs. 32 ± 8) and model for end-stage liver disease (MELD) (24 ± 9 vs. 34 ± 11) scores and serum lactate on admission (4.9 ± 3.1 vs. 8.9  ± 5.3), P < 0.001 for all. Survivors were less likely to receive inappropriate initial antimicrobial therapy (0% vs. 25%, P = 0.013) and received appropriate antimicrobial therapy earlier [median 1.8 (1.1-5.2) vs. 9.5 (3.9-14.3) h, P < 0.001]. After adjusting for covariates, APACHEII [OR, odds ratio 1.45 (1.04-2.02) per 1 unit increment, P = 0.03], lactate [OR 2.34 (1.04-5.29) per unit increment, P = 0.04] and time delay to appropriate antimicrobials [OR 1.86 (1.10-3.14) per hour increment, P = 0.02] were significantly associated with increased mortality.
  
  
  CONCLUSIONS
  Cirrhotic patients with septic shock secondary to spontaneous bacterial peritonitis have high mortality (>80%). Each hour of delay in appropriate antimicrobial therapy was associated with a 1.86 times increased hospital mortality. Admission APACHEII and serum lactate also significantly impacted hospital mortality. Earlier initiation of appropriate antimicrobial therapy could substantially improve outcome.
authors.affiliation: Division of Critical Care Medicine and Gastroenterology/Hepatology, University of Alberta, Edmonton, AB, Canada; Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, AB, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Karvellas
authors.forename: J G
authors.initials: JG
authors.lastname: Abraldes
authors.forename: Y M
authors.initials: YM
authors.lastname: Arabi
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy*; D005260:Female; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D016017:Odds Ratio; D010538:Peritonitis / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000890:Anti-Infective Agents