This suggests that our assessment of the impact of acquired-BSI o

This suggests that our assessment of the impact of acquired-BSI on survival should be regarded as an upper-estimate of any effect.Finally, because of the relatively low incidence of ICU-acquired BSI in our population, neither ICU-acquired BSI would account for only 5% of deaths, that is 1% excess mortality in the total population. This observation has several implications for randomized controlled trials of interventions aimed at decreasing mortality by preventing ICU-acquired BSI. For example, a putative untargeted intervention capable of preventing 50% of ICU-acquired BSI would be expected to reduce the overall mortality of ICU patients staying for longer than 72 hours by only 0.5%. Accordingly, even a very effective intervention would have to be administered to 200 patients to save one life.

This effect is impossible to test in any feasibly sized randomized controlled trial (in excess of 100,000 patients would be required for adequate power). Interventions to prevent BSI could have a greater impact on survival by impacting sub-clinical, undiagnosed, or localized infection. However, the strength of such effects would need to be quantified if investigators wish to be assured that interventional studies were adequately sized. Our data do suggest that use of formally diagnosed BSI as a surrogate or secondary endpoint in untargeted interventional studies may not be feasible.Study strengths and weaknessesThis study has several strengths. We used a large sample of patients. Data were collected by dedicated data collectors and electronically stored and were thus not amenable to manipulation or bias.

Similarly, microbiological data were collected as part of patient care. We assessed the independent contribution of BSI to patient outcome, providing useful information for trial design and for the assessment of the relevant interventional literature.On the other hand, our study also has some weaknesses. Its findings may not be directly generalizable to differing microbiological environments worldwide. However, its results are comparable with those in similar studies conducted in the USA and Europe suggesting a degree of external validity. During the 11-year study period changes in case-mix, clinical workload, and clinical practice could have affected incidence and outcome of ICU-acquired BSI. However, no trend was evident on inspection of the yearly data (see Additional file 1).

By examining this time-span we were able to include data from over 6,000 ICU admissions Brefeldin_A making this one of the largest studies of BSI in intensive care.We did not have detailed clinical information including exact trigger for drawing blood cultures, antimicrobial therapy, response to treatment, and cause of death. Nor could we determine whether individual episodes of BSI represented true infections.

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