RESULTS

1. Risk Factors and Mortality Attributable to Clostridium difficile PCR-Ribotype 027 Infections During a Large Outbreak in North of France. G.Birgand a, K.Blanckaert b, F.Barbut d, F.Puisieux c, B.Grandbastien a a Infection Control Unit, Lille Teaching Hospital, France, b Regional coordinating center for nosocomial infection control, Paris, France, c GeriatricGerontology Unit, Lille Teaching Hospital, France, d National reference laboratory for anaerobic bacteria and C. difficile, St Antoine Hospital, Paris, France METHODS BACKGROUND • Risk factors study: • Multicentric match (1:3) case-control study among 10 hospitals including 33 cases and 99 control patients between June 1, and December 1, 2006 to determinerisk factors of CDI027. • - A case was a patient died with a CDI027 hospital acquired • - A control was a patient died without CDI matched on the age and ward of hospitalization. • Strains isolated were characterized as 027 after ribotyping. • Clinical and biological data about patients were collected with a standardized form. Missing values were managed in order to limit bias. • Attributable mortality study: • Mortality attributable to CDI027 on 43 cases and 94 control patients. - A case was defined as a patient died with hospital-acquired CDI027 • - A control was a patient alive during the study with CDI other than PCR-ribotype 027. • Univariate (Mann-Withney, 2-tailed Fischer’s exact tests) and a multivariate analysis (logistic regression) • Proportions attributable risk (PAR) using odds ratio. • Clostridium difficile: anaerobic strict spore forming bacterium • Responsible for 15 to 25% of antibiotic associated diarrhea in developed countries and virtually all cases of pseudomembranous colitis (1). • Since 2002: - emergence of a hypervirulent strain namedClostridium difficile PCR-ribotype 027 represented 80% of all strains isolated in Quebec and 50% in USA (2,3). - 5 to 25 CDI per 1000 elective bed days - attributable mortality estimated to 16.7% in Quebec (4,5). • This study evaluated risk factors of CDI027 and determined the fraction of death potentially associated with CDI027 during a large outbreak in North of France. RESULTS • Sex-ratio (M/F) = 0.7. • Mean age was 82 years old without significance difference between cases and controls (p=0.96). • Risk factors of CDI027: - previous hospitalization (OR=4.2; 95%CI=1.8-10.1), • - arterial hypertension (OR=3.05; 95%CI=1.1-8.1), • - chronic renal failure (OR=2.9; 95%CI=1.3-6.7), • - dementia (OR=2.8; 95%CI=1.2-6.3), • - diabetes (OR=3.1; 95%CI=1.3-7.5), • - malnutrition (OR=2.6; 95%CI=1.1-6.1) and • - ofloxacine treatment (OR=3.8; 95%CI=1.6-9.1). • Any associations regarding biological factors (albumin, protide, hematocrite), the dependence score ADL and the Charlson score, the length of hospitalization or the place of hospitalization (acute vs long stay units). • Proportion of death attributable to CDI027 = - 40.2%(IC95=-0.37 – 68.9%) with crude analysis - 44%(IC95=-0.57 – 73%) after adjustment on other variables like previous hospitalization, innutrition, dependence score and prescription of ceftriaxone. CONCLUSION • A previous hospitalization was the main risk factor of CDI027. Infected patients were significantly more affected by chronic comorbidities. Origins of hospital acquisitions are linked to several facts favoring the cross-transmission : a low health state, the proximity to other patients, an intensive nursing and medical cares. • An assessment of attributable mortality has been performed in 2003 in Quebec. Similarly to our study, the group cases was characterized with more hospital histories than control patients. However, differences were found between both studies. - the population studied by Pepin was in better overall health state and, contrary to our study because any differences of comorbidities were determined. - the choice of cases were done on clinical and biological characteristics but without typing of strains. - analysis was based on an univariate study without inclusion of confusion factors. In consequence, the rate of associated mortality in our study (44%) was higher than . • The attributable mortality of CDI027 is difficult to evaluate and is probably underestimated. The best way to manage CDI027 is the prevention of cross-transmission. • The control of CDI027 outbreaks is possible. It is actually the case in France but the survey need to be followed to prevent the reemergence of this new strain in the north of this country. • Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2007 Jul 3;147(1):69-70. • Loo VG, Poirier L, Miller MA and al. A predominantly clonal multi-institutional outbreak of Clostridium difficile associated diarrhea with high morbidity and mortality. N Eng J Med 2005 8;353(23):2442-9. • Mc Donald LC, Killgore GE, Thompson A, Owens RC, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Eng J Med 2005;353:2433-41. • Agence de la santé Public Canada http://publications.msss.gouv.qc.ca/acrobat/f/documentation/2006/06-209-05no8.pdf (consulté le 29/06/07) • Pépin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 2005;173:1037-42. ICAAC, 12-15th of September 2009, San Francisco