This finding is particularly interesting, because the protopathic bias of the study was limited, as all cases had necrotizing fasciitis and all controls had severe post-varicella skin or soft tissue infections. As far as we know, our study is the first case-control selleck chem inhibitor investigation to focus on adults with community-acquired bacterial infections. Because the incidence of skin and soft tissue infections in ICUs is lower than that of lung or urinary tract infections [20], we included patients with many kinds of severe bacterial infections generally admitted to ICUs. The main site of infection was lung, for which fewer patients were given NSAIDs than for other infected sites, followed by urinary tract.Several possible explanations can be suggested for our inability to find a link between NSAID use and increased risk for sepsis during bacterial infection.

First, the sites of infection and micro-organisms that we identified, especially the low incidence of skin and soft tissue infections and consequently of streptococcal infections, differ from those most frequently identified in studies that found a link between NSAID and sepsis. We included various kinds of bacterial community-acquired infections, and among the 16 case/control pairs with skin and soft tissue infections Streptococcus pyogenes was identified in just seven cases and one control. Second, more microbiological documentation was available for cases than controls. However, this was not surprising, because the incidence of bacteraemia is usually higher in severe sepsis and septic shock, and because lung samples are more frequently available in patients with mechanical ventilation than in those without.

The resulting high rate of undocumented infection in the control group may have biased the results of the study.Finally, it is possible that we underestimated NSAID use among the cases. However, we assumed that more cases than controls took NSAIDs because the cases were more severely ill, and that NSAIDs were prescribed or self-administered to manage pain or fever. Such underestimation of NSAID use could have been due to the greater difficulty of assessing drug use in severely ill patients than in controls with mild infection, whose interviews provided more accurate information. Family questioning and analysis of initial prescriptions were mostly used in cases, and direct questioning in controls.

Other possible explanations for our negative findings Cilengitide are as follows: the study might have been underpowered (for instance, as a result of overestimation of NSAID use in cases); there may have been a sampling bias if the true population using NSAIDs was not representative of either the cases or the controls; and the patients with the most severe septic shock might have had no time to use NSAIDs.