Among the cases, the median time from the first signs of infection to prescription of effective antibiotic therapy was twice as long for NSAID users as for nonusers (Figure (Figure2).2). This was in agreement with the observations reported by Zerr and coworkers [19], kinase inhibitor Ponatinib who found a longer duration of secondary symptoms before hospitalization in NSAID-exposed than in NSAID-unexposed patients [19]. These findings suggest that NSAIDs probably delay the prescription of effective antibiotic therapy because they may mask the progression of disease by suppressing the inflammatory response induced by the infection [21,22]. This is a very important consideration, because delay in diagnosis and consequently in the administration of effective antibiotic therapy was recently shown to be one of the main risk factors for mortality [23].

The potentially harmful effect of NSAIDs may vary, depending on whether patients receive effective antibiotic therapy. Although this was not taken into account in our study, we observed higher mortality, albeit not significantly so, in NSAID-exposed patients. Certain other authors aimed to demonstrate, in contrast, that NSAIDs have a beneficial effect during sepsis, as observed in animals, and that inhibition of cyclo-oxygenase activity improves survival and reduces the physiological abnormalities caused by sepsis [22]. In adults given effective antibiotic therapy for sepsis, some investigators found no difference in clinical outcomes between NSAID users and nonusers, despite a decrease in prostacyclin metabolites in users [24-26].

However, the latter findings do not rule out the possibility that NSAIDs might be harmful in patients given ineffective antibiotic therapy. In any case, these drugs may predispose to severe bacterial infections because they inhibit leucocyte adherence, phagocytosis and bactericidal activity in vitro [22]. In addition, because NSAIDs have been found to increase inflammatory cytokine production in animal and human studies [24,27,28], and because the mortality rate for sepsis correlates with high interleukin-6 and tumour necrosis factor-�� levels, the use of prostaglandin inhibitors in sepsis may be harmful. From this point of view, it might be useful to study infections that are more directly linked to the impairment of granulocyte function, such as fasciitis, extensive abscesses or collections of bacteria from different sites, rather than severe sepsis or septic shock, which are mainly the consequence of the systemic inflammatory reaction.

ConclusionsThe prescribed or self-administered use of NSAIDs is frequent during evolving bacterial infection, but in the present study it did not differ between patients with mild community acquired-infection and those with severe sepsis or septic shock. Our results therefore do not support the hypothesis that, Drug_discovery during bacterial community-acquired infection, NSAIDs increase the risk for severe sepsis or septic shock.