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Systematic review and meta-analysis
Meta-analysis based on limited data shows no evidence to support the guideline recommendation for early administration of antibiotics in severe sepsis and septic shock
  1. Brian Casserly1,2,
  2. Ailish Hannigan2
  1. 1 University Hospital, Limerick, Ireland;
  2. 2 GEMS, University of Limerick, Limerick, Ireland
  1. Correspondence to : Dr Brian Casserly, University Hospital, Limerick, Ireland; brian_casserly{at}

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Commentary on: OpenUrlCrossRefPubMed.


The use of recombinant activated protein C was given a grade B recommendation in severe sepsis in the 2004 edition of the surviving sepsis campaign (SSC) guidelines.1 This initial recommendation was based on the PROWESS trial but subsequent negative randomised controlled trials prompted withdrawal of the drug from the market. This highlights how even the most thoughtful synthesis of the available evidence can be misleading. This has lead, rightly or wrongly, to questioning the evidence base supporting other recommendations within SSC guidelines.


This was a systematic review and meta-analysis of data from studies of patients with severe sepsis or septic shock to establish the association between timing of antibiotics and mortality. Because of the expected limited number of clinical trials in this area, both observational studies and randomised controlled trials (RCT) were included. The primary outcome was mortality. The effects on mortality of antibiotic administration within 3 h …

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  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.