Michael Tvede

Procalcitonin increase in early identification of critically ill patients at high risk of mortality.

Objective:To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients. Design:Prospective observational cohort study. Setting:Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark. Patients:Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit. Interventions:Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level. Measurements and Main Results:Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3–2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4–2.4); after 2 days increase, 2.2 (95% confidence interval 1.6–3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0–3.8). Conclusions:A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.

Mortality in enterococcal bloodstream infections increases with inappropriate antimicrobial therapy

Enterococcus species are common in nosocomial bloodstream infections and their incidence is rising. Although well recognized in several serious bacterial infections, the influence of appropriate antimicrobial therapy in enterococcal bacteraemia has not been fully settled. The aim of the study was to determine whether administration of inappropriate antibiotics in enterococcal bacteraemia is an independent risk factor for mortality, among other known and suspected risk factors. We conducted a cohort study of E. faecalis/faecium bacteraemia during a 3-year period at a single tertiary care hospital in Denmark. Patients with growth of non-enterococcus co-pathogens apart from the enterococcal bacteraemia were also included, as were patients with repeated enterococcal bacteraemia. Time to appropriate antimicrobial therapy was counted from the first episode. Appropriate antibiotic therapy was defined as any therapy with documented clinical effect, in vitro activity and a minimum treatment length of 6 days. Multivariate regression models were built to determine the independent risk factors for mortality. We included 196 patients with enterococcal bacteraemia. Appropriate antibiotics for at least 6 days were administered in 146 of these (74%). Thirty-day mortality was 26%. Multivariate logistic regression identified independent predictors of 30-day all-cause mortality: appropriate antimicrobial therapy for ≥ 6 days (odds ratio for mortality 0.33, 0.14-0.79), ICU admission (4.2, 1.7-10), thrombocytopenia (3.9, 1.6-9.3), chronic liver failure (3.3, 1.1-10) and age ≥ 60 years (2.2, 0.99-5.0). Antibiotics not appropriately covering enterococci are frequently administered empirically in suspected bloodstream infections. Inappropriate antibiotic therapy was an independent risk factor for mortality in enterococcal bacteraemia.