Tigecycline Exhibits Inhibitory Activity againstClostridium difficilein the Colon of Mice and Does Not Promote Growth or Toxin Production

Abstract

ABSTRACTTigecycline is a broad-spectrum glycylcycline antibiotic with potentin vitroactivity againstClostridium difficile. We used a mouse model to test the hypothesis that tigecycline has a low propensity to promote colonization and toxin production byC. difficiledue to inhibitory activity in the colon. Mice (5 to 8 per group) received subcutaneous injections of tigecycline (low and high doses) alone or in combination with clindamycin for 6 days. Growth of and toxin production by 3 strains ofC. difficile(tigecycline MICs ≤ 0.012 μg/ml) were measured in cecal contents collected 6 h or 3 days after the final antibiotic dose. Antibiotic concentrations were measured using a bioassay, and concentrations of total anaerobes andBacteroidesspp. were measured. The effects of tigecycline on rendering mice susceptible to colonization with and reducing the burden ofC. difficilewere also examined. In comparison to saline controls, clindamycin promoted the growth ofC. difficile(P< 0.001) in cecal contents, whereas tigecycline did not. Tigecycline did not suppress total anaerobes orBacteroidesspp. in comparison to saline controls. Concurrent administration of tigecycline prevented clindamycin-induced promotion ofC. difficilein cecal contents collected 6 h or 3 days (high dose only) after the final antibiotic dose. Tigecycline did not promote the establishment of colonization in mice, yet it did not reduce concentrations ofC. difficilein animals with established colonization. In summary, tigecycline did not promote the growth of or toxin production byC. difficile, probably due to inhibitory activity againstC. difficileand relative sparing of indigenous anaerobic microflora.