The Surviving Sepsis Campaign strongly recommends initiating antibiotic therapy within the first hour of recognition of severe sepsis, selleckchem AZD9291 after suitable samples have been obtained for cultures [6].Nevertheless, although antibiotic therapy is the cornerstone in the treatment of sepsis, the optimal antimicrobial strategy has not been defined. Few data are available about antibiotic prescription patterns used most in severe sepsis.Furthermore, the advantages and disadvantages of combination therapy compared with monotherapy are controversial, and studies comparing the two approaches have mainly been limited to bacteremia, pneumonia, or serious Pseudomonas aeruginosa infections [7-9]. Importantly, a recent retrospective study concluded that certain combinations of antimicrobials, including antimicrobials with different targets, improve survival in patients with septic shock [10].

We present a secondary analysis of the Edusepsis study, which enrolled all patients with severe sepsis and septic shock admitted to the participating ICUs during 2 months in 2005 and 4 months in 2006. Our aims are (a) to describe the patterns of empiric antimicrobial therapy, analyzing the differences between community-acquired and nosocomial infections; and (b) to compare the impact on mortality of combination therapy, including at least two antimicrobials with different mechanisms of action, with that of monotherapy and other combinations of antimicrobials.Materials and methodsDesign of the studyWe conducted a secondary analysis of the Edusepsis study, a Spanish national multicenter before-and-after study involving 77 ICUs [11].

In this study, carried out between November 2005 and 2007, data were collected before and after a 2-month educational intervention based on the Surviving Sepsis Campaign guidelines; this approach to improving treatment of severe sepsis is cost-effective [12]. Each participating centers’ research and ethical-review boards approved the study, and patients remained anonymous. The need for informed consent was waived in view of the observational and anonymous nature of the study.The study included all patients in these ICUs with severe sepsis or septic shock. The study design is described in detail elsewhere [11]. In brief, severe sepsis was defined as sepsis associated with organ dysfunction unexplained by other causes.

Septic shock was defined Carfilzomib as sepsis associated with systolic blood pressure <90 mm Hg, mean arterial pressure <65 mm Hg, or a reduction in systolic blood pressure >40 mm Hg from baseline despite adequate volume resuscitation. Patients in whom the onset of severe sepsis could not be determined were excluded from the analysis. The approach to data collection and the quality-control measures to assure data reliability also are described elsewhere [11,12].