title: IMPACT OF TIGECYCLINE VERSUS OTHER ANTIBIOTICS ON THE FECAL METABOLOME AND ON COLONIZATION RESISTANCE TOCLOSTRIDIUM DIFFICILEIN MICE.
abstract: BACKGROUND
  The glycylcycline antibiotic tigecycline may have a relatively low propensity to promoteClostridium difficileinfection in part because it causes less disruption of the indigenous intestinal microbiota than other broad-spectrum antibiotics. We used a mouse model to compare the effects of tigecycline versus other commonly used antibiotics on colonization resistance toC. difficileand on the metabolic functions of the intestinal microbiota.
  
  
  METHODS
  To assessin vivocolonization resistance toC. difficile, mice were challenged with oralC. difficilespores 1, 7, or 12 days after completion of 3 days of treatment with subcutaneous saline, tigecycline, ceftriaxone, piperacillin-tazobactam, or linezolid. Levels of bacterial metabolites in fecal specimens of mice treated with the same antibiotics were analyzed using non-targeted metabolic profiling by gas chromatograph (GC)/mass spectrometry (MS) and ultra-high performance liquid chromatography-tandem MS (UPLC-MS/MS).
  
  
  RESULTS
  All of the antibiotics disrupted colonization resistance toC. difficilewhen challenge occurred 2 days after treatment. Only piperacillin/tazobactam mice had disturbed colonization resistance at 7 days after treatment. All of the antibiotics altered fecal metabolites in comparison to controls, but tigecycline caused significantly less alteration than the other antibiotics, including less suppression of multiple amino acids, bile acids, and lipid metabolites.
  
  
  CONCLUSIONS
  Tigecycline, linezolid, and ceftriaxone caused transient disruption of colonization resistance toC. difficile, whereas piperacillin/tazobactam caused disruption that persisted for 7 days post-treatment. Tigecycline caused less profound alteration of fecal bacterial metabolites than the other antibiotics, suggesting that the relatively short period of disruption of colonization resistance might be related in part to reduced alteration of the metabolic functions of the microbiota.
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve University School of Medicine, Cleveland, OH; Geriatric Research, Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, OH.
authors.forename: Robin L P
authors.initials: RL
authors.lastname: Jump
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve University School of Medicine, Cleveland, OH.
authors.forename: David
authors.initials: D
authors.lastname: Kraft
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve University School of Medicine, Cleveland, OH.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hurless
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve University School of Medicine, Cleveland, OH.
authors.forename: Alex
authors.initials: A
authors.lastname: Polinkovsky
authors.affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve University School of Medicine, Cleveland, OH; Geriatric Research, Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, OH.
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Donskey
keywords: Clostridium difficile; Tigecycline; ceftriaxone; colonization resistance; linezolid; metabolomics; piperacillin/tazobactam