Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Jan;71(1):213-9.
doi: 10.1093/jac/dkv300. Epub 2015 Oct 3.

Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection

D N Gerding  1 , D W Hecht  2 , T Louie  3 , C E Nord  4 , G H Talbot  5 , O A Cornely  6 , M Buitrago  7 , E Best  8 , S Sambol  2 , J R Osmolski  2 , H Kracker  9 , H H Locher  9 , P Charef  9 , M Wilcox  8
Affiliations
Clinical Trial

Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection

D N Gerding et al. J Antimicrob Chemother. 2016 Jan.

Abstract

Objectives: 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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Distribution of cadazolid MICs at baseline for pooled cadazolid dosages (mITT analysis set).
See this image and copyright information in PMC

References

    1. McDonald LC, Killgore GE, Thompson A et al. . An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353: 2433–41. - PubMed
    1. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009; 7: 526–36. - PubMed
    1. Burke KE, Lamont JT. Clostridium difficile infection: a worldwide disease. Gut Liver 2014; 8: 1–6. - PMC - PubMed
    1. Jones AM, Kuijper EJ, Wilcox MH. Clostridium difficile: a European perspective. J Infect 2013; 66: 115–28. - PubMed
    1. Borgmann S, Kist M, Jakobiak T et al. . Increased number of Clostridium difficile infections and prevalence of Clostridium difficile PCR ribotype 001 in southern Germany. Euro Surveill 2008; 13: pii=19057. - PubMed

Publication types

MeSH terms

Associated data