title: Typing and susceptibility of bacterial isolates from the fidaxomicin (OPT-80) phase II study for C. difficile infection.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) has been increasing in incidence and severity in recent years, coincident with the spread of a "hypervirulent" strain, REA type BI (ribotype 027, PFGE NAP 1). Exacerbating the problem has been the observation that metronidazole may be showing decreased effectiveness, particularly in the more severe cases. Fidaxomicin is an 18-membered macrocycle currently in phase 3 trials for the treatment of C. difficile infection (CDI). An open-label, phase II study in CDI patients has been completed and the clinical results published. C. difficile organisms were isolated from patient stool specimens and typed by restriction endonuclease analysis (REA) in order to determine the frequency and susceptibility of the C. difficile isolates and their response to treatment.
  
  
  METHODS
  Fecal samples were plated on CCFA agar for isolation of C. difficile. These isolates were tested for susceptibility to fidaxomicin, vancomycin, and metronidazole using CLSI agar dilution methods and were typed by REA.
  
  
  RESULTS
  C. difficile was isolated from 38 of 49 subjects and 16 (42%) were the epidemic C. difficile BI group. The BI strain was distributed approximately equally in the three dosing groups. Overall antibiotic susceptibilities were consistent with the previously reported MIC(90) values for the three antibiotics tested, but the MIC(90) of BI strains was two dilutions higher than non-BI strains for metronidazole and vancomycin (for both antibiotics, MIC(90) was 2 microg/mL vs. 0.5 microg/mL, P<0.01 for metronidazole, P=NS for vancomycin). Clinical cure for BI isolates (11/14, 79%) was not significantly different from non-BI isolates (21/22, 95%).
  
  
  CONCLUSIONS
  These results underscore the high prevalence of the BI epidemic strain and demonstrate that mild to moderate CDI infection as well as severe disease can be caused by these strains. Fidaxomicin cure rates for subjects with BI and with non-BI strains are similar, although the small numbers of subjects preclude a robust statistical comparison.
authors.affiliation: RM Alden Research Lab, Culver City, CA, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Citron
authors.forename: F
authors.initials: F
authors.lastname: Babakhani
authors.forename: E J C
authors.initials: EJ
authors.lastname: Goldstein
authors.forename: K
authors.initials: K
authors.lastname: Nagaro
authors.forename: S
authors.initials: S
authors.lastname: Sambol
authors.forename: P
authors.initials: P
authors.lastname: Sears
authors.forename: Y-K
authors.initials: YK
authors.lastname: Shue
authors.forename: D N
authors.initials: DN
authors.lastname: Gerding
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015373:Bacterial Typing Techniques; D016360:Clostridioides difficile / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D000091402:Prohibitins; D021521:Ribotyping; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D006027:Glycosides; C487655:OPT 80; C000717331:PHB2 protein, human; D000091402:Prohibitins; D004262:DNA Restriction Enzymes