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

Crit Care Med. Sept 2010 V.38  N.9  p.1773-85.

Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G, Keenan S, Wood G, Arabi Y, Feinstein D, Kumar A, Dodek P, Kravetsky L, Doucette S; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group.

Collaborators (57)Wood KE, Laupland K, Kramer A, Penner C, Light B, Sharma S, Lapinsky S, Marshall J, Dial S, Bagshaw S, Skrobik I, Patel G, Gurka D, Zanotti S, Dellinger P, Feinstein D, Guzman J, Al Shirawi N, Al Memish Z, Ronald J, Suleman M, Gulati H, Halmarson E, Suppes R, Peters C, Sullivan K, Bohmeier R, Muggaberg S, Kravetsky L, Ahsan MW, Singh A, Carter L, Wiebe K, Kolesar L, Richards J, Jaswal D, Chou H, Kosick T, Fu W, Chan C, Ren JJ, Bahrainian M, Haque Z, Torshizi OA, Paulin H, Khan F, Kumar R, Harvey J, Kim C, Li J, Campbell L, Taiberg L, Schorr C, Tchokonte R, Gonzales C, Serrano N, Delgra S.

Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada. akumar61@yahoo.com

Comment in:

Crit Care Med. 2010 Sep;38(9):1906-8.

http://www.ncbi.nlm.nih.gov/pubmed/20724888

Crit Care Med. 2010 Sep;38(9):1905-6.

http://www.ncbi.nlm.nih.gov/pubmed/20585123?dopt=Abstract

Abstract

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.

abstract

http://www.ncbi.nlm.nih.gov/pubmed/20639750?dopt=Abstract