Universität zu Köln

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. and Wilcox, M. (2016). Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C-difficile infection. J. Antimicrob. Chemother., 71 (1). S. 213 - 220. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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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 (mu g/g) on day 5 was 884 (101-2710), 1706 (204-4230) and 3226 (1481-12aEuroS600) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gerding, D. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hecht, D. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Louie, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nord, C. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Talbot, G. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, O. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buitrago, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Best, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sambol, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Osmolski, J. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kracker, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Locher, H. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Charef, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilcox, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-291015
DOI:	10.1093/jac/dkv300
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	71
Number:	1
Page Range:	S. 213 - 220
Date:	2016
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-VITRO ACTIVITY; EPIDEMIOLOGY; DISEASE; STRAIN; METRONIDAZOLE; RESISTANCE; COLITIS Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29101