Table 2Comparison of NSAID and aspirin use by cases versus controlsFinally, there was still no difference between the two groups after adjustment for pre-existing diseases or for treatment centre (data not shown). Few diabetic patients were included in the study (only 20 pairs). There was no difference between their NSAID or aspirin consumption and that of the rest of the population sellekchem studied. However, more nondiabetic controls than cases used aspirin (11% versus 4%; OR = 0.36; P = 0.04). For the three main sites of infection (lung, urinary tract, and skin or soft tissue), NSAID use varied depending on the site. Twice as many cases and controls with urinary tract or skin and soft tissue infections used NSAIDs compared with those who had lung infections.

We did not observe any difference between cases and controls for any of the sites studied.Consequently, in the light of these findings, only the cases were studied. Among the cases, the time from the first signs to the prescription of effective antibiotic therapy was longer for NSAID users than for nonusers (median [95% CI]: 6 days, 3 days to 7 days for NSAID users versus 3 days, 2 days to 3 days for NSAID nonusers; P = 0.02; Figure Figure2).2). Among the cases, the mortality rate in NSAID users was 27% and that in nonusers was 23% (P = 0.58).Figure 2Time from the first signs of infection to effective antibiotic therapy. Shown is a comparison of the times from the first signs of infection to effective antibiotic therapy for cases; the compared groups were cases using nonsteroidal anti-inflammatory …

DiscussionThe findings presented here do not support the hypothesis that NSAID exposure during evolving bacterial infection is associated with an increased risk for severe sepsis or septic shock. However, in patients with severe sepsis or septic shock we observed that NSAID use is associated with a longer time from the first signs of infection to prescription of effective antibiotic therapy.As stated in the Introduction (above), several case reports for patients admitted to ICUs [7-9] have suggested that NSAID treatment might increase the severity of infection and lead to shock and multiple organ failure. This is because life-threatening infections �C mainly streptococcal, especially necrotizing fasciitis �C have been described following NSAID use [3,5], as have infections with other organisms such as Staphylococcus spp.

or Gram-negative bacilli, albeit less frequently [15]. However, unlike these case reports, Batimastat case-control studies are designed to establish an association between an event and a risk factor and to quantify the risk involved. Most of the case-control studies relevant to the present investigation concerned the link between NSAID exposure of children with varicella and skin or soft tissue infections [16-19].