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Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection.
J Antimicrob Chemother. 2016 Jan; 71(1):213-9.JA

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.

Authors+Show Affiliations

Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA dale.gerding2@va.gov.Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA.University of Calgary, Calgary, Alberta, Canada.Karolinska Institute, Stockholm, Sweden.Talbot Advisors, Anna Maria, FL, USA.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.Idaho Falls Infectious Diseases, Idaho Falls, ID, USA.Leeds General Infirmary, Leeds, UK.Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA.Loyola University, Maywood, IL, USA Edward Hines Jr VA Hospital, Hines, IL, USA.Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.Leeds General Infirmary, Leeds, UK.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26433782

Citation

Gerding, D N., et al. "Susceptibility of Clostridium Difficile Isolates From a Phase 2 Clinical Trial of Cadazolid and Vancomycin in C. Difficile Infection." The Journal of Antimicrobial Chemotherapy, vol. 71, no. 1, 2016, pp. 213-9.
Gerding DN, Hecht DW, Louie T, et al. Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection. J Antimicrob Chemother. 2016;71(1):213-9.
Gerding, D. N., Hecht, D. W., Louie, T., Nord, C. E., Talbot, G. H., Cornely, O. A., Buitrago, M., Best, E., Sambol, S., Osmolski, J. R., Kracker, H., Locher, H. H., Charef, P., & Wilcox, M. (2016). Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection. The Journal of Antimicrobial Chemotherapy, 71(1), 213-9. https://doi.org/10.1093/jac/dkv300
Gerding DN, et al. Susceptibility of Clostridium Difficile Isolates From a Phase 2 Clinical Trial of Cadazolid and Vancomycin in C. Difficile Infection. J Antimicrob Chemother. 2016;71(1):213-9. PubMed PMID: 26433782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection. AU - Gerding,D N, AU - Hecht,D W, AU - Louie,T, AU - Nord,C E, AU - Talbot,G H, AU - Cornely,O A, AU - Buitrago,M, AU - Best,E, AU - Sambol,S, AU - Osmolski,J R, AU - Kracker,H, AU - Locher,H H, AU - Charef,P, AU - Wilcox,M, Y1 - 2015/10/03/ PY - 2015/03/31/received PY - 2015/08/23/accepted PY - 2015/10/5/entrez PY - 2015/10/5/pubmed PY - 2016/10/7/medline SP - 213 EP - 9 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 71 IS - 1 N2 - 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. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/26433782/Susceptibility_of_Clostridium_difficile_isolates_from_a_Phase_2_clinical_trial_of_cadazolid_and_vancomycin_in_C__difficile_infection_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkv300 DB - PRIME DP - Unbound Medicine ER -