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. DATA SOURCES: 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. STUDY SELECTION: Randomized or observational studies of antimicrobial therapy of serious bacterial infections potentially associated with sepsis or septic shock. Fifty studies met entry criteria. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSION: 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.
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. DATA SOURCES: 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. STUDY SELECTION: Randomized or observational studies of antimicrobial therapy of serious bacterial infections potentially associated with sepsis or septic shock. Fifty studies met entry criteria. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSION: 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: Etienne de Montmollin; Lila Bouadma; Nathalie Gault; Bruno Mourvillier; Eric Mariotte; Sarah Chemam; Laurent Massias; Emmanuelle Papy; Florence Tubach; Michel Wolff; Romain Sonneville Journal: Intensive Care Med Date: 2014-04-01 Impact factor: 17.440
Authors: Ignacio Martin-Loeches; Maria Deja; Despoina Koulenti; George Dimopoulos; Brian Marsh; Antonio Torres; Michael S Niederman; Jordi Rello Journal: Intensive Care Med Date: 2013-01-29 Impact factor: 17.440
Authors: Andre C Kalil; Mark L Metersky; Michael Klompas; John Muscedere; Daniel A Sweeney; Lucy B Palmer; Lena M Napolitano; Naomi P O'Grady; John G Bartlett; Jordi Carratalà; Ali A El Solh; Santiago Ewig; Paul D Fey; Thomas M File; Marcos I Restrepo; Jason A Roberts; Grant W Waterer; Peggy Cruse; Shandra L Knight; Jan L Brozek Journal: Clin Infect Dis Date: 2016-07-14 Impact factor: 9.079