De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock.

BACKGROUND: Mortality rates among patients with sepsis, severe sepsis or septic shock ranges from 27% to 54%. Empirical broad-spectrum antimicrobial treatment is aimed at achieving adequate antimicrobial therapy and thus reducing mortality. However, there is a risk that empirical broad-spectrum antimicrobial treatment can expose patients to overuse of antimicrobials. De-escalation has been proposed as a strategy to replace empirical broad-spectrum antimicrobial treatment with a narrower antimicrobial therapy. This is done by either changing the pharmacological agent or discontinuing a pharmacological combination according to the patient's microbial culture results.

OBJECTIVES: To evaluate the effectiveness and safety of de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock caused by any micro-organism.

SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 8); MEDLINE via PubMed (from inception to August 2010); EMBASE (from inception to August 2010); LILACS (from inception to August 2010); Current Controlled Trials and bibliographic references of relevant studies. We also contacted the main authors in the area. We applied no language restriction.

SELECTION CRITERIA: We planned to include randomized controlled trials comparing de-escalation (based on culture results) versus standard therapy for adults with sepsis, severe sepsis or septic shock. The primary outcome was mortality (at 28 days, hospital discharge or the end of the follow-up period). Studies including patients initially treated with an empirical but not adequate antimicrobial therapy were not considered for inclusion.

DATA COLLECTION AND ANALYSIS: Two authors planned to independently select and extract data and evaluate methodological quality of all studies. We planned to use relative risk (risk ratio) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals. We planned to use the random-effects statistical model when the estimate effects of two or more studies could be combined in a meta-analysis.

MAIN RESULTS: We retrieved 436 references via the search strategy. No randomized controlled trials testing de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock could be included in this review.

AUTHORS' CONCLUSIONS: There is no adequate, direct evidence as to whether de-escalation of antimicrobial agents is effective and safe for adults with sepsis, severe sepsis or septic shock. Therefore, it is not possible to either recommend or not recommend the de-escalation of antimicrobial agents in clinical practice for septic patients. This uncertainty warrants further research via randomized controlled trials or cohort studies.