title: Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI.
abstract: The microflora-sparing properties of fidaxomicin were examined during the conduct of a randomized clinical trial comparing vancomycin 125 mg 4 times per day versus fidaxomicin 200 mg twice per day for 10 days as treatment of Clostridium difficile infection (CDI). Fecal samples were obtained from 89 patients (45 received fidaxomicin, and 44 received vancomycin) at study entry and on days 4, 10, 14, 21, 28, and 38 for quantitative cultures for C. difficile and cytotoxin B fecal filtrate concentrations. Additionally, samples from 10 patients, each receiving vancomycin or fidaxomicin, and 10 samples from healthy controls were analyzed by quantitative real-time polymerase chain reaction with multiple group-specific primers to evaluate the impact of antibiotic treatment on the microbiome. Compared with controls, patients with CDI at study entry had counts of major microbiome components that were 2-3-log(10) colony-forming units (CFU)/g lower. In patients with CDI, fidaxomicin allowed the major components to persist, whereas vancomycin was associated with a further 2-4-log(10) CFU reduction of Bacteroides/Prevotella group organisms, which persisted to day 28 of the study, and shorter term and temporary suppression of both Clostridium coccoides and Clostridium leptum group organisms. In the posttreatment period, C. difficile counts similarly persisted in both study populations, but reappearance of toxin in fecal filtrates was observed in 28% of vancomycin-treated patient samples (29 of 94), compared with 14% of fidaxomicin-treated patient samples (13 of 91; P = .03). Similarly, 23% of vancomycin-treated patients (10 of 44) and 11% of fidaxomicin-treated patients (5 of 44) had recurrence of CDI. Whereas vancomycin and fidaxomicin are equally effective in resolving CDI symptoms, preservation of the microflora by fidaxomicin is associated with a lower likelihood of CDI recurrence.
authors: Department of Medicine, University of Calgary, Foothills Medical Center, 1403 29th St NW, Calgary, Canada. thomas.louie@albertahealthservices.ca
authors: Thomas J
authors: TJ
authors: Louie
authors: Kris
authors: K
authors: Cannon
authors: Brendan
authors: B
authors: Byrne
authors: Judy
authors: J
authors: Emery
authors: Linda
authors: L
authors: Ward
authors: Melissa
authors: M
authors: Eyben
authors: Walter
authors: W
authors: Krulicki
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D058491:Bacterial Load; D001427:Bacterial Toxins / Q000032:analysis / Q000378:metabolism*; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology; D003603:Cytotoxins / Q000032:analysis / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D000077732:Fidaxomicin; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D057230:Limit of Detection; D054892:Metagenome; D012336:RNA, Ribosomal, 16S / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055502:Secondary Prevention; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D003603:Cytotoxins; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D014640:Vancomycin; D000077732:Fidaxomicin