Spatial clustering and livestock exposure as risk factor for community-acquired Clostridium difficile infection.

OBJECTIVES: Clostridium difficile infections (CDI) account for 1.5% of diarrhoeic episodes in patients attending a general practitioner in the Netherlands, but its sources are unknown. We searched for community clusters to recognize localized point sources of CDI. METHODS: Between October 2010 and February 2012, a community-based prospective nested case-control study was performed in three laboratories in the Netherlands with a study population of 2 810 830 people. Bernoulli spatial scan and space-time permutation models were used to detect spatial and/or temporal clusters of CDI. In addition, a multivariate conditional logistic regression model was constructed to test livestock exposure as a supposed risk factor in CDI patients without hospital admission within the previous 12 weeks (community-acquired (CA) CDI). RESULTS: In laboratories A, B and C, 1.3%, 1.8% and 2.1% of patients with diarrhoea tested positive for CDI, respectively. The mean age of CA-CDI patients (n = 124) was 49 years (standard deviation, 22.6); 64.5% were female. No spatial or temporal clusters of CDI cases were detected compared to C. difficile-negative diarrhoeic controls. Except for one false-positive signal, no spatiotemporal interaction amongst CDI cases was found. Livestock exposure was not related to CA-CDI (odds ratio, 0.99; 95% confidence interval, 0.44-2.24). Ten percent of CA-CDIs was caused by PCR ribotype 078, spatially dispersed throughout the study area. CONCLUSIONS: The absence of clusters of CDI cases in a community cohort of diarrhoeic patients suggests a lack of localized point sources of CDI in the living environment of these patients.

Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a nested case-control study.

Clostridium difficile infections (CDIs) are frequent in hospitals, but also seem to increase in the community. Here, we aim to determine the incidence of CDI in general practice and to evaluate current testing algorithms for CDI. Three Dutch laboratories tested all unformed faeces (12,714) for C. difficile when diagnostic testing (for any enteric pathogen) was requested by a general practitioner (GP). Additionally, a nested case-control study was initiated, including 152 CDI patients and 304 age and sex-matched controls. Patients were compared using weighted multivariable logistic regression. One hundred and ninety-four samples (1.5%) were positive for C. difficile (incidence 0.67/10,000 patient years). This incidence was comparable to that of Salmonella spp. Compared with diarrhoeal controls, CDI was associated with more severe complaints, underlying diseases, antibiotic use and prior hospitalization. In our study, GPs requested a test for C. difficile in 7% of the stool samples, thereby detecting 40% of all CDIs. Dutch national recommendations advise testing for C. difficile when prior antibiotic use or hospitalization is present (18% of samples). If these recommendations were followed, 61% of all CDIs would have been detected. In conclusion, C. difficile is relatively frequent in general practice. Currently, testing for C. difficile is rare and only 40% of CDI in general practice is detected. Following recommendations that are based on traditional risk factors for CDI, would improve detection of CDI.

Cardioprotective effects of nucleoside transport inhibition in rabbit hearts.

The cardioprotective effects of a nucleoside transport inhibitor, R75231, were investigated in the isolated rabbit heart. The hearts were subjected to 20 minutes of global normothermic ischemia followed by reperfusion. Before ischemia either solvent (group 1), 5 mumol/L of adenosine (group 2), or 0.64 mg/L R75231 (group 3) was added to the perfusate. Preischemic hemodynamics were not changed by treatment, except for an increase in coronary flow in the adenosine group (126% of control; p less than 0.05). Upon reperfusion, coronary flow was depressed in the controls (72% of the preischemic control values), increased in the adenosine group (113%) and unchanged in the R75231 group (89%). Functional recovery was significantly better in the adenosine group as well as in the R75231 group as compared with the controls (p less than 0.05). Cardiac output was 74% of the preischemic control value in the R75231 group, 67% in the adenosine group, and only 38% in the controls. Analysis of the coronary effluent after reperfusion showed a significant inhibition of rapid release of purines and a reverse of the adenosine/inosine ratio in the R75231 group as compared with the others. We conclude that R75231 has a cardioprotective effect that is probably related to accumulation of endogenous adenosine.