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Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin.
J Antimicrob Chemother. 2018 08 01; 73(8):2078-2084.JA

Abstract

Objectives

We evaluated the antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from participants in a Phase 2 study of ridinilazole, a novel targeted-spectrum agent for treatment of C. difficile infection.

Methods

Participants received ridinilazole (200 mg twice daily) or vancomycin (125 mg four times daily) for 10 days (ClinicalTrials.gov: NCT02092935). The MICs of ridinilazole and comparators for C. difficile isolates from stool samples were determined by agar dilution. Toxin gene profiling was performed by multiplex PCR and ribotype identification by capillary electrophoresis.

Results

Eighty-nine isolates were recovered from 88/100 participants (one participant had two strains at baseline). The median colony count (cfu/g stool) was 1.9 × 104 (range: 2.5 × 102-7.0 × 106). Twelve participants (three received ridinilazole and nine received vancomycin) experienced recurrence, confirmed by immunoassays for free toxin in stool samples. The ribotype of eight out of nine isolates obtained at recurrence matched those of the initial isolates. All isolates, including those obtained at recurrence, were susceptible to ridinilazole within the expected range [median (range) MIC: 0.12 (0.06-0.5) mg/L]. The median (range) vancomycin MIC was 1 (0.5-4.0) mg/L. At baseline, 13.6% and 13.3% of samples in the ridinilazole and vancomycin groups were positive for VRE, increasing to 23.7% and 29.7% by day 40, respectively. Common ribotypes included 014-20 (14 isolates), 027 (13), 106 (7), 002 (7), 078-126 (4), 001 (4), 087 (3) and 198 (3). Toxin gene profiling of nearly all baseline isolates (98.9%) revealed a binary toxin gene (cdtA/cdtB) prevalence of 35%.

Conclusions

Ridinilazole potently inhibited recovered C. difficile isolates. Recurrence was not associated with altered susceptibility.

Authors+Show Affiliations

Division of Geographic Medicine and Infectious Diseases and Department of Medicine, Tufts Medical Center, Boston, MA, USA. Tufts University School of Medicine, Boston, MA, USA.Division of Geographic Medicine and Infectious Diseases and Department of Medicine, Tufts Medical Center, Boston, MA, USA.Division of Geographic Medicine and Infectious Diseases and Department of Medicine, Tufts Medical Center, Boston, MA, USA. Tufts University School of Medicine, Boston, MA, USA.Division of Geographic Medicine and Infectious Diseases and Department of Medicine, Tufts Medical Center, Boston, MA, USA.Division of Geographic Medicine and Infectious Diseases and Department of Medicine, Tufts Medical Center, Boston, MA, USA.Department of Microbiology and Immunology, Montana State University, Bozeman, MT, USA.Summit Therapeutics Plc, Abingdon, Oxfordshire, UK.

Pub Type(s)

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

Language

eng

PubMed ID

29718329

Citation

Snydman, David R., et al. "Antimicrobial Susceptibility and Ribotypes of Clostridium Difficile Isolates From a Phase 2 Clinical Trial of Ridinilazole (SMT19969) and Vancomycin." The Journal of Antimicrobial Chemotherapy, vol. 73, no. 8, 2018, pp. 2078-2084.
Snydman DR, McDermott LA, Thorpe CM, et al. Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin. J Antimicrob Chemother. 2018;73(8):2078-2084.
Snydman, D. R., McDermott, L. A., Thorpe, C. M., Chang, J., Wick, J., Walk, S. T., & Vickers, R. J. (2018). Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin. The Journal of Antimicrobial Chemotherapy, 73(8), 2078-2084. https://doi.org/10.1093/jac/dky135
Snydman DR, et al. Antimicrobial Susceptibility and Ribotypes of Clostridium Difficile Isolates From a Phase 2 Clinical Trial of Ridinilazole (SMT19969) and Vancomycin. J Antimicrob Chemother. 2018 08 1;73(8):2078-2084. PubMed PMID: 29718329.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin. AU - Snydman,David R, AU - McDermott,Laura A, AU - Thorpe,Cheleste M, AU - Chang,Justin, AU - Wick,Jenna, AU - Walk,Seth T, AU - Vickers,Richard J, PY - 2017/11/30/received PY - 2018/03/20/accepted PY - 2018/5/3/pubmed PY - 2019/10/23/medline PY - 2018/5/3/entrez SP - 2078 EP - 2084 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 73 IS - 8 N2 - Objectives: We evaluated the antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from participants in a Phase 2 study of ridinilazole, a novel targeted-spectrum agent for treatment of C. difficile infection. Methods: Participants received ridinilazole (200 mg twice daily) or vancomycin (125 mg four times daily) for 10 days (ClinicalTrials.gov: NCT02092935). The MICs of ridinilazole and comparators for C. difficile isolates from stool samples were determined by agar dilution. Toxin gene profiling was performed by multiplex PCR and ribotype identification by capillary electrophoresis. Results: Eighty-nine isolates were recovered from 88/100 participants (one participant had two strains at baseline). The median colony count (cfu/g stool) was 1.9 × 104 (range: 2.5 × 102-7.0 × 106). Twelve participants (three received ridinilazole and nine received vancomycin) experienced recurrence, confirmed by immunoassays for free toxin in stool samples. The ribotype of eight out of nine isolates obtained at recurrence matched those of the initial isolates. All isolates, including those obtained at recurrence, were susceptible to ridinilazole within the expected range [median (range) MIC: 0.12 (0.06-0.5) mg/L]. The median (range) vancomycin MIC was 1 (0.5-4.0) mg/L. At baseline, 13.6% and 13.3% of samples in the ridinilazole and vancomycin groups were positive for VRE, increasing to 23.7% and 29.7% by day 40, respectively. Common ribotypes included 014-20 (14 isolates), 027 (13), 106 (7), 002 (7), 078-126 (4), 001 (4), 087 (3) and 198 (3). Toxin gene profiling of nearly all baseline isolates (98.9%) revealed a binary toxin gene (cdtA/cdtB) prevalence of 35%. Conclusions: Ridinilazole potently inhibited recovered C. difficile isolates. Recurrence was not associated with altered susceptibility. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/29718329/Antimicrobial_susceptibility_and_ribotypes_of_Clostridium_difficile_isolates_from_a_Phase_2_clinical_trial_of_ridinilazole__SMT19969__and_vancomycin_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dky135 DB - PRIME DP - Unbound Medicine ER -