title: Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection.
abstract: OBJECTIVE
  The aim of this study was to evaluate the susceptibilities of Clostridium difficile isolates to cadazolid, a novel antibiotic for the treatment of C. difficile infection.
  
  
  METHODS
  Ribotyping and susceptibilities were determined for C. difficile isolates from a multicentre, double-blind, Phase 2 study of oral cadazolid in patients with C. difficile infection (NCT01222702, ClinicalTrials.gov; EudraCT 2010-020941-29, European Clinical Trials Database). Patients were randomized to receive 250, 500 or 1000 mg of cadazolid twice daily or 125 mg of vancomycin four times daily, for 10 days. MICs of cadazolid, vancomycin, fidaxomicin, linezolid and moxifloxacin were determined at baseline for all patients and post-baseline for patients with clinical failure or recurrence, using the agar dilution method.
  
  
  RESULTS
  Seventy-eight of 84 patients had an evaluable toxigenic C. difficile isolate at baseline. The most frequent PCR ribotype was 027 (15.4%). Cadazolid MICs for baseline isolates (including epidemic strain 027) ranged from 0.06 to 0.25 mg/L. Baseline cadazolid MICs were similar to those of fidaxomicin and lower than those of vancomycin, linezolid and moxifloxacin. For each clinical outcome group (clinical cure, clinical failure, sustained clinical response and clinical failure or recurrence), the baseline cadazolid MIC range was 0.06-0.25 mg/L. Mean (min-max) cadazolid faecal concentration (μg/g) on day 5 was 884 (101-2710), 1706 (204-4230) and 3226 (1481-12 600) for the doses 250, 500 and 1000 mg, respectively.
  
  
  CONCLUSIONS
  For all cadazolid doses, the faecal concentration was in excess of several thousand-fold the MIC90 for C. difficile. The MIC of cadazolid for all C. difficile isolates, including epidemic strains, was low and in the same narrow range regardless of treatment outcome.
authors.affiliation: Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA dale.gerding2@va.gov.
authors.forename: D N
authors.initials: DN
authors.lastname: Gerding
authors.affiliation: Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Hecht
authors.affiliation: University of Calgary, Calgary, Alberta, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Louie
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: C E
authors.initials: CE
authors.lastname: Nord
authors.affiliation: Talbot Advisors, Anna Maria, FL, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Talbot
authors.affiliation: Department of Internal Medicine, University Hospital of Cologne, Cologne, Germany Clinical Trials Centre Cologne, University of Cologne, Cologne, Germany Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: O A
authors.initials: OA
authors.lastname: Cornely
authors.affiliation: Idaho Falls Infectious Diseases, Idaho Falls, ID, USA.
authors.forename: M
authors.initials: M
authors.lastname: Buitrago
authors.affiliation: Leeds General Infirmary, Leeds, UK.
authors.forename: E
authors.initials: E
authors.lastname: Best
authors.affiliation: Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sambol
authors.affiliation: Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Osmolski
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Kracker
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: H H
authors.initials: HH
authors.lastname: Locher
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Charef
authors.affiliation: Leeds General Infirmary, Leeds, UK.
authors.forename: M
authors.initials: M
authors.lastname: Wilcox
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016360:Clostridioides difficile / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000494:pharmacology; D021521:Ribotyping; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; C000591679:cadazolid; D014640:Vancomycin