Document Detail


Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.
MedLine Citation:
PMID:  20639750     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern.
OBJECTIVE: To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock.
DESIGN: Retrospective, propensity matched, multicenter, cohort study.
SETTING: Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007.
SUBJECTS: A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated.
MEASUREMENTS AND MAIN RESULTS: The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with beta-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days.
CONCLUSION: Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.
Authors:
Anand Kumar; Ryan Zarychanski; Bruce Light; Joseph Parrillo; Dennis Maki; Dave Simon; Denny Laporta; Steve Lapinsky; Paul Ellis; Yazdan Mirzanejad; Greg Martinka; Sean Keenan; Gordon Wood; Yaseen Arabi; Daniel Feinstein; Aseem Kumar; Peter Dodek; Laura Kravetsky; Steve Doucette;
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Critical care medicine     Volume:  38     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2010-09-27     Revised Date:  2011-07-13    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1773-85     Citation Subset:  AIM; IM    
Affiliation:
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada. akumar61@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Aged
Anti-Bacterial Agents / administration & dosage,  therapeutic use*
Drug Therapy, Combination
Female
Humans
Male
Middle Aged
Propensity Score
Retrospective Studies
Shock, Septic / drug therapy*,  microbiology
Survival Rate*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents
Investigator
Investigator/Affiliation:
Kenneth E Wood / ; Kevin Laupland / ; Andreas Kramer / ; Charles Penner / ; Bruce Light / ; Satendra Sharma / ; Steve Lapinsky / ; John Marshall / ; Sandra Dial / ; Sean Bagshaw / ; Ionna Skrobik / ; Gourang Patel / ; Dave Gurka / ; Sergio Zanotti / ; Phillip Dellinger / ; Dan Feinstein / ; Jorge Guzman / ; Nehad Al Shirawi / ; Ziad Al Memish / ; John Ronald / ; Mustafa Suleman / ; Harleena Gulati / ; Erica Halmarson / ; Robert Suppes / ; Cheryl Peters / ; Katherine Sullivan / ; Rob Bohmeier / ; Sheri Muggaberg / ; Laura Kravetsky / ; Muhammed Wali Ahsan / ; Amrinder Singh / ; Lindsey Carter / ; Kym Wiebe / ; Laura Kolesar / ; Jody Richards / ; Danny Jaswal / ; Harris Chou / ; Tom Kosick / ; Winnie Fu / ; Charlena Chan / ; Jia Jia Ren / ; Mozdeh Bahrainian / ; Ziaul Haque / ; Omid Ahmadi Torshizi / ; Heidi Paulin / ; Farah Khan / ; Runjun Kumar / ; Johanne Harvey / ; Christina Kim / ; Jennifer Li / ; Latoya Campbell / ; Leo Taiberg / ; Christa Schorr / ; Ronny Tchokonte / ; Catherine Gonzales / ; Norrie Serrano / ; Sofia Delgra /
Comments/Corrections
Comment In:
Crit Care Med. 2010 Sep;38(9):1905-6   [PMID:  20724887 ]
Crit Care Med. 2010 Sep;38(9):1906-8   [PMID:  20724888 ]
Crit Care Med. 2011 Jun;39(6):1604; author reply 1604-5   [PMID:  21610652 ]
Crit Care Med. 2011 Feb;39(2):423-4; author reply 424-5   [PMID:  21248539 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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