Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.
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.


METHODS
Retrospective, propensity matched, multicenter, cohort study.


METHODS
Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007.


METHODS
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.


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.


CONCLUSIONS
Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.
Kumar
Anand
A
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada. akumar61@yahoo.com
Zarychanski
Ryan
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Light
Bruce
B
Parrillo
Joseph
J
Maki
Dennis
D
Simon
Dave
D
Laporta
Denny
D
Lapinsky
Steve
S
Ellis
Paul
P
Mirzanejad
Yazdan
Y
Martinka
Greg
G
Keenan
Sean
S
Wood
Gordon
G
Arabi
Yaseen
Y
Feinstein
Daniel
D
Kumar
Aseem
A
Dodek
Peter
P
Kravetsky
Laura
L
Doucette
Steve
S
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D012189:Retrospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology; D015996:Survival Rate; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents