The
glycylcycline antibiotic tigecycline was approved in 2005 for the treatment of complicated skin and
soft tissue infections and complicated
intra-abdominal infections.
Tigecycline is broadly active against both Gram-negative and Gram-positive microorganisms, including Clostridium difficile.
Tigecycline has a low MIC against C. difficile in vitro and thus may represent an alternate treatment for C. difficile
infection (CDI). To assess the use of
tigecycline for treatment of established CDI, 5- to 8-week-old C57BL/6 mice were colonized with C. difficile strain 630. After C. difficile colonization was established, mice (n = 10 per group) were treated with either a 5-day course of
tigecycline (6.25 mg/kg every 12 h subcutaneously) or a 5-day course of
vancomycin (0.4 mg/ml in
drinking water) and compared to infected, untreated control mice. Mice were evaluated for clinical signs of CDI throughout treatment and at 1 week posttreatment to assess potential for disease development. Immediately following a treatment course, C. difficile was not detectable in the feces of
vancomycin-treated mice but remained detectable in feces from
tigecycline-treated and untreated control mice. Toxin activity and histopathological
inflammation and
edema were observed in the ceca and colons of untreated mice;
tigecycline- and
vancomycin-treated mice did not show such changes directly
after treatment. One week after the conclusion of either
antibiotic treatment, C. difficile load, toxin activity, and histopathology scores increased in the cecum and colon, indicating that C. difficile-associated disease occurred. In vitro growth studies confirmed that subinhibitory concentrations of
tigecycline were able to suppress toxin activity and spore formation of C. difficile, whereas
vancomycin did not. Taken together, these data show how
tigecycline is able to alter C. difficile pathogenesis in a mouse model of CDI.