title: Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis.
abstract: It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups.
  
  
  CONCLUSIONS
  In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured.
authors: Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. yaseenarabi@yahoo.com
authors: Yaseen M
authors: YM
authors: Arabi
authors: Saqib I
authors: SI
authors: Dara
authors: Ziad
authors: Z
authors: Memish
authors: Abdulmajeed
authors: A
authors: Al Abdulkareem
authors: Hani M
authors: HM
authors: Tamim
authors: Nehad
authors: N
authors: Al-Shirawi
authors: Joseph E
authors: JE
authors: Parrillo
authors: Peter
authors: P
authors: Dodek
authors: Stephen
authors: S
authors: Lapinsky
authors: Daniel
authors: D
authors: Feinstein
authors: Gordon
authors: G
authors: Wood
authors: Sandra
authors: S
authors: Dial
authors: Sergio
authors: S
authors: Zanotti
authors: Anand
authors: A
authors: Kumar
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy; D002170:Canada; D016001:Confidence Intervals; D003422:Critical Care; D004359:Drug Therapy, Combination; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007902:Length of Stay; D016014:Linear Models; D008103:Liver Cirrhosis / Q000150:complications*; D016015:Logistic Models; D008297:Male; D008508:Medication Errors; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy; D016017:Odds Ratio; D012189:Retrospective Studies; D012529:Saudi Arabia; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014481:United States
chemical_list: D000890:Anti-Infective Agents