title: Effects of tigecycline and vancomycin administration on established Clostridium difficile infection.
abstract: 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.
authors.affiliation: Department of Internal Medicine/Division of Infectious Diseases, The University of Michigan, Ann Arbor, Michigan, USA caseythe@med.umich.edu.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Theriot
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Cassie A
authors.initials: CA
authors.lastname: Schumacher
authors.affiliation: Department of Internal Medicine/Division of Infectious Diseases, The University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Bassis
authors.affiliation: Department of Internal Medicine/Division of Infectious Diseases, The University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Seekatz
authors.affiliation: Department of Internal Medicine/Division of Infectious Diseases, The University of Michigan, Ann Arbor, Michigan, USA Department of Microbiology and Immunology, The University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002432:Cecum / Q000382:microbiology; D016360:Clostridioides difficile / Q000187:drug effects*; D003106:Colon / Q000382:microbiology; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078304:Tigecycline; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline