Overview of C difficile Infections - Dr Steve Brecher - November 2010 Symposium


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Presented by Dr. Brecher at the 40th Annual Symposium "Diagnostic and Clinical Challenges of 20th Century Microbes", held on Nov 18, 2010 in Philadelphia.

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  • Slide Originally, it was thought that the administration of antimicrobial therapy following asymptomatic colonization resulted in C. difficile -associated diarrhea. However, later findings suggested that patients who are colonized with C. difficile are at a reduced risk of developing active infection. 1 Those data led to the revised hypothesis of C. difficile pathogenesis, as shown in this slide. After hospitalization or admission to a long-term healthcare facility, patients are at an increased risk of exposure to C. difficile. The administration of antimicrobials or other agents that may alter the colonic flora (eg, chemotherapy) render the patient susceptible and lead to the development of C. difficile disease, asymptomatic C. difficile colonization, or nothing. The incubation period after exposure in a susceptible patient is less than 1 week. 1 Do not exclude the diagnosis of C. difficile in patients who have received other agents that can potentially alter the colonic flora. (This is the exception; the vast majority of patients with CDI will have received antimicrobials.) Johnson S, Gerding DN. Clostridium difficile -associated diarrhea. Clin Infect Dis. 1998;26:1027-1036.
  • Slide The CDC has reported a new strain of C. difficile . 3 Various methods of classification exist for the epidemic strain. The epidemic strain is characterized as toxinotype III, North American pulsed-field gel electrophoresis (PFGE) type 1, and polymerase chain reaction (PCR)-ribotype 027 (NAP1/027). 1 In Quebec, the strain is classified as Pulsovar A and was determined to be identical to NAP1. 2 This new strain produces both toxin A and toxin B and they are not “missed” by laboratories that use toxin A immunoassays. This strain has caused multiple recent outbreaks of C. difficile infection across the United States and in Montreal, Canada, and the United Kingdom. Other features of the new strain include high-level resistance to fluoroquinolones, which may be related to increased virulence. 2,4 The epidemic strain also produces binary toxin. However, the significance of binary toxin is unknown at this time. This strain appears to produce greater amounts of toxins A and B and has a deletion in the tcdC gene, which potentially downregulates toxin production. 1 This slide shows the polymorphisms and deletions in the tcdC variants that have been identified in toxinotype III strains (the tcdC protein may downregulate the production of toxins A and B), which may result in a decreased ability to regulate toxin production, causing dramatically increased amounts of toxins A and B. This association requires further verification. 4-6 Warny M, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet . 2005;366:1079-1084. Hubert B, et al. A portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile -associated disease in Quebec. Clin Infect Dis. 2007;44:238-244. CDC. Frequently asked questions about a new strain of Clostridium difficile. Fact Sheet, July 2005. McDonald LC, et al. An epidemic, toxin gene-variant strain of Clostridium difficile . N Engl J Med. 2005;353:2433-2441. Spigaglia P, Mastrantonio P. Molecular analysis of the pathogenicity locus and polymorphism in the putative negative regulator of toxin production (TcdC) among Clostridium difficile clinical isolates. J Clin Microbiol . 2002;40:3470-3475. Rupnik M, et al. Revised nomenclature of Clostridium difficile toxins and associated genes. J Med Microbiol. 2005;54:113-117.
  • Slide The figure depicts the in vitro production of toxins A and B by C. difficile isolates of toxinotype 0 (red line) and toxinotype III (blue line). These data are based on observations published recently by Warny and colleagues using isolates from 124 patients with CDAD in Quebec, Canada. Additional isolates from recent outbreaks were obtained from the US Centers for Disease Control and Prevention, Montreal, and the United Kingdom. As shown, the peak concentration of toxin A was 16 times higher in the toxinotype III strain than in type 0 strains, and the concentration of toxin B was 23 times higher. Furthermore, control strains (type 0) produced toxin during the stationary phase, whereas type III strains produced toxin during the log and stationary phases. 1 Warny M, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet . 2005;366:1079-1084.
  • Swindell et al paper Xpert = 19 Pos, BDGO = 18 Pos
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