Reducing Mortality in Severe Sepsis and Septic Shock

Andrew T. Levinson, M.D., M.P.H.; Brian P. Casserly, M.D.; Mitchell M. Levy, M.D.


Semin Respir Crit Care Med. 2011;32(2):195-205. 

In This Article


Timely administration of antibiotics is an independent predictor of survival in patients with severe sepsis. A very large retrospective study of over 18,000 patients admitted with community-acquired pneumonia found a significant reduction in in-hospital and 30-day mortality (adjusted OR 0.85) if antibiotics were given within 4 hours of arrival at the hospital.[61] Another large, multicenter, retrospective cohort study found that in 2731 patients with persistent or refractory hypotension each hour of delay in the administration of appropriate antibiotics (ie, the eventual cultured organism had in vitro susceptibility) was associated with a 7.6% mean decrease in survival. The same study found that survival was 83% if appropriate antibiotics were administered within 30 minutes of the first occurrence of hypotension but declined to 42% if antibiotics were not administered until the sixth hour after first documentation of hypotension.[62] A recent analysis by Gaieski and colleagues examined the relationship between mortality and time to administration of antibiotics in 261 septic patients presenting to a single urban academic medical department. The retrospective cohort study found that if appropriate antibiotics were administered within 1 hour of triage, compared with greater than 1 hour from triage, there was a 13.7% decrease in mortality.[63,64]

Appropriate initial choice of antibiotic coverage has also been shown to be an independent predictor of survival in patients with severe sepsis. Appropriate antibiotic therapy is defined as that which has in vitro activity against the isolated organism. In the recent retrospective cohort study by Gaieski and colleagues, patients who received appropriate antibiotics as prescribed by an institution-specific antibiotic nomogram had a 17.5% reduction in mortality compared with those who did not receive appropriate antibiotics.[63,64] One smaller study found a significantly increased relative risk of death (2.18) if patients initially received inadequate antibiotic coverage in the ICU for bloodstream infections.[65] Given the challenges of increasing drug-resistant pathogens, selecting appropriate combinations of antibiotics may be crucial. A recent retrospective study of 760 patients with severe sepsis or septic shock found that those patients who received initial combination therapy covering gram-negative bacteria had significantly lower rates of hospital mortality (36%) compared with those that did not (52%).[66] Because almost all of the evidence for timely and appropriate antibiotic use is from cohort studies, it is possible that the relationship between mortality and timely and appropriate antibiotics is indirect and is a surrogate marker for other components of quality care.[64] The SSC recommends the selection of initial empirical antibiotic therapy that has known susceptibility for all likely pathogens.[14]


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