title: Prevention of fatal Clostridium difficile-associated disease during continuous administration of clindamycin in hamsters.
abstract: Clostridium difficile-associated disease (CDAD) due to toxigenic strains is prevented in hamsters by colonization by nontoxigenic C. difficile after administration of clindamycin (Cm). To prevent CDAD during treatment with antibiotics, we gave a Cm-resistant nontoxigenic C. difficile strain, M13 (minimal inhibitory concentration [MIC], >256 microg/mL), and a Cm-susceptible strain, M3 (MIC, 0.5 microg/mL), to hamsters receiving Cm daily for days 1-5. Either M13 or M3 was given orogastrically (1 x 10(6) spores/day) to each hamster in 3 groups of 5 each, on either day 3, days 3-5, or days 3-7. M13 colonized at a higher rate and faster than did M3 (P<.001). When hamsters were challenged by toxigenic strain B1 on days 5, 7, or 9, M13 prevented CDAD in 100% of the hamsters. M3 protected no hamsters challenged by B1 on day 5, 20% on day 7, and 100% on day 9. M13 contains the erm(B) resistance gene but not the mobilizable element Tn5398. The benefits of use of Cm-resistant nontoxigenic C. difficile to prevent CDAD must be balanced against the risk that resistance might be transferred to other enteric bacteria.
authors.affiliation: Infectious Disease Section, Department of Medicine, Veterans Affairs Chicago Health Care System, Lakeside Division, Chicago, Illinois, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Merrigan
authors.forename: Susan P
authors.initials: SP
authors.lastname: Sambol
authors.forename: Stuart
authors.initials: S
authors.lastname: Johnson
authors.forename: Dale N
authors.initials: DN
authors.lastname: Gerding
mesh_terms: D018829:Adhesins, Bacterial / Q000032:analysis / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002981:Clindamycin / Q000008:administration & dosage / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics*; D006224:Cricetinae; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial; D004761:Enterocolitis, Pseudomembranous / Q000473:pathology / Q000517:prevention & control*; D008647:Mesocricetus; D008780:Methyltransferases / Q000032:analysis / Q000235:genetics; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D002981:Clindamycin; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase