title: A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study.
abstract: OBJECTIVE
  To assess whether a potential benefit with combination antibiotic therapy is restricted to the most critically ill subset of patients, particularly those with septic shock.
  
  
  METHODS
  OVID MEDLINE (1950-October 2009), EMBASE (1980-October 2009), the Cochrane Central Register of Controlled Trials (to third quarter 2009), the ClinicalTrial.gov database, and the SCOPUS database.
  
  
  METHODS
  Randomized or observational studies of antimicrobial therapy of serious bacterial infections potentially associated with sepsis or septic shock. Fifty studies met entry criteria.
  
  
  METHODS
  Study design, mortality/clinical response, and other variables were extracted independently by two reviewers. When possible, study datasets were split into mutually exclusive groups with and without shock or critical illness.
  
  
  RESULTS
  Although a pooled odds ratio indicated no overall mortality/clinical response benefit with combination therapy (odds ratio, 0.856; 95% confidence interval, 0.71-1.03; p = .0943; I = 45.1%), stratification of datasets by monotherapy mortality risk demonstrated substantial benefit in the most severely ill subset (monotherapy risk of death >25%; odds ratio of death, 0.51; 95% confidence interval, 0.41-0.64; I = 8.6%). Of those datasets that could be stratified by the presence of shock/critical illness, the more severely ill group consistently demonstrated increased efficacy of a combination therapy strategy (odds ratio, 0.49; 95% confidence interval, 0.35-0.70; p < .0001; I = 0%). An increased risk of death was found in low-risk patients (risk of death <or=15% in the monotherapy arm) exposed to combination therapy (odds ratio, 1.53; 95% confidence interval, 1.16-2.03; p = .003; I = 8.2%). Meta-regression indicated that efficacy of combination therapy was dependent only on the risk of death in the monotherapy group.
  
  
  CONCLUSIONS
  Combination antibiotic therapy improves survival and clinical response of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients.
authors.affiliation: Medical Microbiology and Pharmacology/Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada. akumar61@yahoo.com
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Nasia
authors.initials: N
authors.lastname: Safdar
authors.forename: Shravan
authors.initials: S
authors.lastname: Kethireddy
authors.forename: Dan
authors.initials: D
authors.lastname: Chateau
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D002423:Cause of Death; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D004359:Drug Therapy, Combination; D004502:Education, Medical, Continuing; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D018570:Risk Assessment; D012772:Shock, Septic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents