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      Risk Factors for and Estimated Incidence of Community-associated Clostridium difficile Infection, North Carolina, USA 1

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          Abstract

          Antimicrobial drug exposure is the most common modifiable risk factor for infection.

          Abstract

          We determined estimated incidence of and risk factors for community-associated Clostridium difficile infection (CA-CDI) among patients treated at 6 North Carolina hospitals. CA-CDI case-patients were defined as adults (>18 years of age) with a positive stool test result for C. difficile toxin and no hospitalization within the prior 8 weeks. CA-CDI incidence was 21 and 46 per 100,000 person-years in Veterans Affairs (VA) outpatients and Durham County populations, respectively. VA case-patients were more likely than controls to have received antimicrobial drugs (adjusted odds ratio [aOR] 17.8, 95% confidence interval [CI] 6.6–48] and to have had a recent outpatient visit (aOR 5.1, 95% CI 1.5–17.9). County case-patients were more likely than controls to have received antimicrobial drugs (aOR 9.1, 95% CI 2.9–28.9), to have gastroesophageal reflux disease (aOR 11.2, 95% CI 1.9–64.2), and to have cardiac failure (aOR 3.8, 95% CI 1.1–13.7). Risk factors for CA-CDI overlap with those for healthcare-associated infection.

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          Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe.

          Michel Warny, Jacques Pépin, Aiqi Fang … (2005)
          Toxins A and B are the primary virulence factors of Clostridium difficile. Since 2002, an epidemic of C difficile-associated disease with increased morbidity and mortality has been present in Quebec province, Canada. We characterised the dominant strain of this epidemic to determine whether it produces higher amounts of toxins A and B than those produced by non-epidemic strains. We obtained isolates from 124 patients from Centre Hospitalier Universitaire de Sherbrooke in Quebec. Additional isolates from the USA, Canada, and the UK were included to increase the genetic diversity of the toxinotypes tested. Isolate characterisation included toxinotyping, pulsed-field gel electrophoresis (PFGE), PCR ribotyping, detection of a binary toxin gene, and detection of deletions in a putative negative regulator for toxins A and B (tcdC). By use of an enzyme-linked immunoassay, we measured the in-vitro production of toxins A and B by epidemic strain and non-dominant strain isolates. The epidemic strain was characterised as toxinotype III, North American PFGE type 1, and PCR-ribotype 027 (NAP1/027). This strain carried the binary toxin gene cdtB and an 18-bp deletion in tcdC. We isolated this strain from 72 patients with C difficile-associated disease (58 [67%] of 86 with health-care-associated disease; 14 [37%] of 38 with community-acquired disease). Peak median (IQR) toxin A and toxin B concentrations produced in vitro by NAP1/027 were 16 and 23 times higher, respectively, than those measured in isolates representing 12 different PFGE types, known as toxinotype 0 (toxin A, median 848 microg/L [IQR 504-1022] vs 54 microg/L [23-203]; toxin B, 180 microg/L [137-210] vs 8 microg/L [5-25]; p<0.0001 for both toxins). The severity of C difficile-associated disease caused by NAP1/027 could result from hyperproduction of toxins A and B. Dissemination of this strain in North America and Europe could lead to important changes in the epidemiology of C difficile-associated disease.
          Article 0 comments Cited 290 times – based on 0 reviews     Review now
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            Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity.

            Jacques Pépin, Louis Valiquette, Marie-Eve Alary … (2004)
            Recent reports suggest that Clostridium difficile colitis may be evolving into a more severe disease. During the second half of 2002 we noted an increase in the number of patients with severe C. difficile-associated diarrhea (CDAD) in our institution. We describe cases of CDAD at our institution over a 13-year period and investigate changes in illness severity. We undertook a retrospective chart review of all cases of CDAD diagnosed at the Centre hospitalier universitaire de Sherbrooke from Jan. 1, 1991, to Dec. 31, 2003. Because the hospital serves a well-defined population of Quebec, we were also able to calculate population-based incidence during this period. We abstracted data on individual patients from patient charts and from hospital and pharmacy computer databases. We defined cases of CDAD as having a positive C. difficile cytotoxicity assay result, or endoscopic or histopathological evidence of pseudomembranous colitis. A case was considered complicated if one or more of the following was observed: megacolon, perforation, colectomy, shock requiring vasopressor therapy, or death within 30 days after diagnosis. A total of 1721 cases of CDAD were diagnosed during the study period. The incidence increased from 35.6 per 100,000 population in 1991 to 156.3 per 100,000 in 2003; among patients aged 65 years or more, it increased from 102.0 to 866.5 per 100,000. The proportion of cases that were complicated increased from 7.1% (12/169) in 1991-1992 to 18.2% (71/390) in 2003 (p < 0.001), and the proportion of patients who died within 30 days after diagnosis increased from 4.7% (8/169) in 1991-1992 to 13.8% (54/390) in 2003 (p < 0.001). A high leukocyte count (20.0 small ha, Cyrillic 10(9)/L or greater) and an elevated creatinine level (200 micromol/L or greater) were strongly associated with adverse outcomes: in 2003, 45 (40.9%) of 110 patients with a high leukocyte count or creatinine level, or both, had complicated CDAD and 28 (25.5%) died within 30 days after diagnosis. After adjustment for age and other confounding factors, patients initially given oral vancomycin therapy had a risk of progression to complicated CDAD that was 79% lower than the risk among patients initially treated with metronidazole (adjusted odds ratio 0.2, 95% confidence interval 0.06-0.8, p = 0.02). An epidemic of CDAD with an increased case-fatality rate has had important consequences on the elderly population of our region. Our observational data suggest that the equivalence of vancomycin and metronidazole in the treatment of CDAD needs to be questioned.
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              Incidence of Clostridium difficile infection in inflammatory bowel disease.

              K Reske, Joseph Rodemann, D Seo … (2007)
              Clostridium difficile-associated disease (CDAD) rates have been increasing. We sought to determine whether CDAD incidence has increased specifically in hospitalized patients with IBD. We also explored possible differences in the risk for and time to presentation of CDAD between IBD and non-IBD patients. We analyzed hospital admissions from 1998-2004 for demographics, length of stay, C difficile infections, and time from admission to a positive C difficile test. We calculated CDAD incidence for non-IBD, all IBD, CD, and UC admissions and used logistic regression to estimate the risk for CDAD. CDAD incidence increased in each group and was higher in all IBD than non-IBD groups. During the observation period, CDAD rates approximately doubled in CD (9.5 to 22.3/1000 admissions) and tripled in UC (18.4 to 57.6/1000). Length of stay was similar among the groups. For all years combined, the adjusted odds ratios for CDAD in all IBD, CD, and UC admissions were 2.9 (95% confidence interval, 2.1-4.1), 2.1 (1.3-3.4), and 4.0 (2.4-6.6), respectively. The median times from admission to a positive C difficile test result for non-IBD, CD, and UC were 4.0, 0.8, and 0.5 days, respectively. CDAD incidence in IBD has increased and is higher than in the non-IBD population. IBD and UC patients in particular have a higher risk for CDAD. C difficile infections in IBD are confirmed predominantly within 48 hours of admission, suggesting most were acquired before hospitalization.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Infect Dis
                Journal ID (publisher-id): EID
                Title: Emerging Infectious Diseases
                Publisher: Centers for Disease Control and Prevention
                ISSN (Print): 1080-6040
                ISSN (Electronic): 1080-6059
                Publication date (Print): February 2010
                Volume: 16
                Issue: 2
                Pages: 198-204
                Affiliations
                [1]Centers for Disease Control and Prevention, Atlanta, Georgia, USA (P.K. Kutty, S.R. Benoit, L.C. McDonald)
                [2]Department of Veterans Affairs Medical Center, Durham, North Carolina, USA (C.W. Woods, S. Naggie, J. Frederick)
                [3]Duke University Medical Center, Durham (C.W. Woods, S. Naggie, S. Evans); Durham County Health Department, Durham (A.C. Sena)
                [4]University of North Carolina, Chapel Hill, North Carolina, USA (A.C. Sena)
                [5]North Carolina Department of Health and Human Services, Raleigh, North Carolina, USA (J. Engel)
                [1 ]Presented in part at the 44th Annual Meeting of the Infectious Diseases Society of America, Toronto, Ontario, Canada, October 12–15, 2006.
                Author notes
                Address for correspondence: L. Clifford McDonald, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop A31, Atlanta, GA 30333, USA; email: cmcdonald1@ 123456cdc.gov
                Article
                Publisher ID: 09-0953
                DOI: 10.3201/eid1602.090953
                PMC ID: 2958012
                PubMed ID: 20113547
                SO-VID: f07f881e-8926-4c2c-acb2-1cfa86f3cba9
                History
                Categories
                Subject: Research

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: risk factors,community,incidence,clostridium difficile,research,enteric infections,bacteria
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: risk factors, community, incidence, clostridium difficile, research, enteric infections, bacteria

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