title: Prevention of Clostridium difficile spore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam.
abstract: BACKGROUND
  Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on C. difficile sporulation in vitro.
  
  
  METHODS
  The reference strains ATCC 9689, 630, VPI 10463, and seven other clinical isolates of C. difficile were used, including three epidemic NAP1/027 isolates. Minimum inhibitory concentrations (MIC) were determined and sporulation was assessed after growth in the absence or presence of ≤0.5x MIC concentrations of each antibiotic.
  
  
  RESULTS
  All strains were sensitive to the antibiotics tested, except ribotype 027 isolates that were resistant to ciprofloxacin (MIC = 128 mg/L). Metronidazole and vancomycin generally did not significantly affect spore production in C. difficile, although vancomycin slightly affected sporulation of a few isolates. Ciprofloxacin inhibited sporulation of ribotype 027 isolates mainly. Interestingly, sub-MIC concentrations of piperacillin/tazobactam reduced spore formation in several isolates. However, the most striking observation was made with tigecycline, with an important reduction of spore formation in most isolates.
  
  
  CONCLUSIONS
  The capacity of C. difficile to sporulate can be significantly affected by certain antibiotics. The reduced sporulation observed with tigecycline and piperacillin/tazobactam might explain why these antibiotics are generally associated with lower risk of C. difficile infections. In addition, the inhibition of sporulation might partly explain the apparent efficacy of tigecycline for treatment of patients with recurrent infection.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Garneau
authors.forename: Louis
authors.initials: L
authors.lastname: Valiquette
authors.affiliation: Département de microbiologie et d'infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3201 rue Jean Mignault, Sherbrooke, Québec J1E 4K8, Canada. Louis-Charles.Fortier@USherbrooke.ca.
authors.forename: Louis-Charles
authors.initials: LC
authors.lastname: Fortier
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002939:Ciprofloxacin / Q000008:administration & dosage; D016360:Clostridioides difficile / Q000187:drug effects*; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D021521:Ribotyping; D013171:Spores, Bacterial; D000078142:Tazobactam; D000078304:Tigecycline; D014640:Vancomycin / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D000077725:Piperacillin, Tazobactam Drug Combination; D002939:Ciprofloxacin; D014640:Vancomycin; D000078304:Tigecycline; D010397:Penicillanic Acid; D008911:Minocycline; D000078142:Tazobactam; D010878:Piperacillin