Infection of Hamsters with Historical and Epidemic BI Types ofClostridium difficile

Abstract

Background. North American and European hospitals have reported outbreaks of Clostridium difficile-associated disease with unexpectedly high mortality caused by a newly recognized group of C. difficile strains, group BI. Our objective was to compare, in hamsters, the virulence of a historical nonepidemic BI type, BI1, with that of 2 recent epidemic BI types, BI6 and BI17, and with that of 2 standard toxigenic strains, K14 and 630.Methods. For each strain, 10 hamsters were given 1 dose of clindamycin, followed 5 days later with 100 C. difficile spores administered by gastric inoculation. Outcomes were recorded.Results. The hamster model demonstrated variations in mean times from inoculation to death (for BI6, 40 h; for BI1, 48 h; for K14, 49 h; for BI17, 69 h; for 630, 102 h; for BI6, BI1, and K14 vs. 630, P Ͻ .01; for BI17 vs. 630, P Ͻ .05) and from colonization to death (for BI1, 7 h; for BI17, 13 h; for BI6, 16 h; for K14, 17 h; for 630, 52 h; for BI1, BI17, BI6, and K14 vs. 630, P Ͻ .01).Conclusion. Group BI strains were not more rapidly fatal than the standard toxinotype 0 strain K14 but were more rapidly fatal than the standard toxinotype 0 strain 630. BI6, the most common BI type in our collection, was particularly virulent in hamsters, consistently causing death within 48 h of inoculation.

Fourteen-Genome Comparison Identifies DNA Markers for Severe-Disease-Associated Strains of Clostridium difficile

“…Six isolates were of the predominant SDA strain type (NAP1), and collection dates ranged from 1984 to 2007. The international CIP 107932 reference isolate (isolated in 1984) and the BI-1 isolate (isolated in Minnesota in 1988 [47]) represented NAP1 isolates predating the CDI epidemic of 2003 to 2007. The other four NAP1 isolates (QCD-32g58, QCD-66c26, QCD-37x79, and QCD-97b34) were collected during the CDI epidemic from three locations across Canada.…”

Cefoperazone-treated mice as an experimental platform to assess differential virulence ofClostridium difficilestrains

“…27 While important insights into the pathogenesis of CDI have been gained from experimental infection of Syrian hamsters, 14,28 one limitation of this model is that animals infected with toxigenic C. difficile strains generally have a uniformly fatal course, reducing the ability to detect differences in virulence. 19,20 In this report, we present a model of CDI that should be useful to show relative differences in the pathogenicity of C. difficile strains. Animals are made susceptible to colonization with C. difficile through the administration of a single antibiotic, cefoperazone.…”

“…15 Our results in cefoperazone treated mice contrasts with the clinical outcome seen in hamsters infected with BI1 and strain 630. 19,20 Infection of hamsters with both of these strains was uniformly fatal, although death occurred more rapidly in animals infected with BI1. Cefoperazone-treated mice infected with a strain 630 have a clinically benign course.…”

“…As a proof of principle we compared the outcome of experimental infection of cefoperazone-treated mice with four C. difficile strains, including those used in past murine models. 16,19,20 In addition to VPI 10463, we also challenged mice with a BI1 strain which is a member of the restriction enzyme analysis (REA) group BI, ribotype 027, from North American isolates NAP1. This strain is an ancestor of the epidemic strain that has appeared in the past decade.…”

Clostridial typhlitis associated with topical antibiotic therapy in a Syrian hamster

“…Upon treatment with clindamycin and inoculation with spores from standard and BI strains, one strain, BI6, was found to be particularly virulent in hamsters, consistently causing death within 48 h of inoculation. 40 In the case reported herein, a fatal clostridial typhlitis occurred in association with topical antibiotic administration. Self-grooming may have resulted in unintentional oral exposure.…”