Impact of an intervention to control Clostridium difficile infection on hospital- and community-onset disease; an interrupted time series analysis.

Strategies to reduce rates of Clostridium difficile infection (CDI) generally recommend isolation or cohorting of active cases and the reduced use of cephalosporin and quinolone antibiotics. Data supporting these recommendations come predominantly from the setting of epidemic disease caused by ribotype 027 strains. We introduced an initiative involving a restrictive antibiotic policy and a CDI-cohort ward at an acute, 820-bed teaching hospital where ribotype 027 strains account for only one quarter of all CDI cases. Antibiotic use and monthly CDI cases in the 12 months before and the 15 months after the initiative were compared using an interrupted time series analysis and segmented regression analysis. The initiative resulted in a reduced level of cephalosporin and quinolone use (22.0% and 38.7%, respectively, both p <0.001) and changes in the trends of antibiotic use such that cephalosporin use decreased by an additional 62.1 defined daily doses (DDD) per month (p <0.001) and antipseudomonal penicillin use increased by 20.7 DDD per month (p = 0.011). There were no significant changes in doxycycline or carbapenem use. Although the number of CDI cases each month was falling before the intervention, there was a significant increase in the rate of reduction after the intervention from 3% to 8% per month (0.92, 95% CI 0.86-0.99, p = 0.03). During the study period, there was no change in the proportion of cases having their onset in the community, nor in the proportion of ribotype 027 cases. CDI cohorting and restriction of cephalosporin and quinolone use are effective in reducing CDI cases in a setting where ribotype 027 is endemic.

Drotrecogin alfa (activated): diffusion from clinical trials to clinical practice.

BACKGROUND AND OBJECTIVE: Although the PROWESS trial demonstrated a mortality benefit, subsequent studies in different patient populations have not reproduced the effect. As a result, concerns have been expressed about the clinical effectiveness of drotrecogin alfa (activated). Therefore the aim of this audit was to review the clinical impact of drotrecogin alfa (activated) when used outside clinical trials. METHODS: A retrospective review of ICU charts and medical records of patients who had received drotrecogin alfa (activated) in the five largest users of drotrecogin alfa (activated) in England. Patients characteristics details at ICU admission and vital status at hospital discharge were recorded. The severity of illness was assessed by the APACHE II score (using first 24 h admission data) and the number of organ dysfunctions. Adverse incidents were recorded and any sequence effect explored. RESULTS: In all, 351 patients received drotrecogin alfa (activated) between December 2002 and November 2005. Of those, 201 (57.2%) were male, and 177 (50.4%) were admitted after recent surgery. The patients' average age was 61.8 yr. The mean admission APACHE II score was 23.3 and the average number of dysfunctional organs on admission was 3.3. The hospital mortality was 46.7% (164 deaths). The expected number of deaths calculated by using the APACHE II risk of death was 173 (49.3%) and by number of sepsis induced organ failures 210 (59.7%). Overall, there were 33 (9.4%) adverse incidents. CONCLUSIONS: Expected mortality derived from both the APACHE II score and organ dysfunctions suggests that drotrecogin alfa (activated) does reduce mortality. Serious adverse incidents occurred in 5.1% patients; however, the direct contributing effect of drotrecogin alfa (activated) cannot be established from this type of audit.