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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 (13) case-control study among
  10 hospitals including 33 cases and 99 control
  patients between June 1, and December 1, 2006 to
  determine risk 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 Fischers
  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 named Clostridium 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 (p0.96).
• Risk factors of CDI027
• - previous hospitalization (OR4.2
  95CI1.8-10.1),
• - arterial hypertension (OR3.05
  95CI1.1-8.1),
• - chronic renal failure (OR2.9
  95CI1.3-6.7),
• - dementia (OR2.8 95CI1.2-6.3),
• - diabetes (OR3.1 95CI1.3-7.5),
• - malnutrition (OR2.6 95CI1.1-6.1) and
• - ofloxacine treatment (OR3.8 95CI1.6-9.1).
  
• 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 3147(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
  8353(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 20053532433-41.
• Agence de la santé Public Canada
  http//publications.msss.gouv.qc.ca/acrobat/f/docu
  mentation/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
  20051731037-42.

ICAAC, 12-15th of September 2009, San Francisco