Tags

Type your tag names separated by a space and hit enter

SMT19969 as a treatment for Clostridium difficile infection: an assessment of antimicrobial activity using conventional susceptibility testing and an in vitro gut model.
J Antimicrob Chemother. 2015 Jan; 70(1):182-9.JA

Abstract

OBJECTIVES

We investigated the efficacy of the novel antimicrobial agent SMT19969 in treating simulated Clostridium difficile infection using an in vitro human gut model.

METHODS

Concentrations of the predominant cultivable members of the indigenous gut microfloras and C. difficile (total and spore counts) were determined by viable counting. Cytotoxin titres were determined using cell cytotoxicity and expressed as log10 relative units (RU). Clindamycin was used to induce simulated C. difficile PCR ribotype 027 infection. Once high-level cytotoxin titres (≥ 4 RU) were observed, SMT19969 was instilled for 7 days. Two SMT19969 dosing regimens (31.25 and 62.5 mg/L four times daily) were evaluated simultaneously in separate experiments. MICs of SMT19969 were determined against 30 genotypically distinct C. difficile ribotypes.

RESULTS

SMT19969 was 7- and 17-fold more active against C. difficile than metronidazole and vancomycin, respectively, against a panel of genotypically distinct isolates (P < 0.05). Both SMT19969 dosing regimens demonstrated little antimicrobial activity against indigenous gut microflora groups except clostridia. SMT19969 inhibited C. difficile growth and repressed C. difficile cytotoxin titres in the gut model.

CONCLUSIONS

These data suggest that SMT19969 is a narrow-spectrum and potent antimicrobial agent against C. difficile. Additional studies evaluating SMT19969 in other models of C. difficile infection are warranted, with human studies to place these gut model observations in context.

Authors+Show Affiliations

Department of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK s.baines2@herts.ac.uk.Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds LS2 9JT, UK.Department of Microbiology, Leeds Teaching Hospitals NHS Trust, The General Infirmary, Old Medical School, Leeds LS1 3EX, UK.Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds LS2 9JT, UK.Summit plc, 85b Park Drive, Milton Park, Abingdon, Oxfordshire OX14 4RY, UK.Leeds Institute for Biomedical and Clinical Sciences, University of Leeds, Leeds LS2 9JT, UK Department of Microbiology, Leeds Teaching Hospitals NHS Trust, The General Infirmary, Old Medical School, Leeds LS1 3EX, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25190720

Citation

Baines, S D., et al. "SMT19969 as a Treatment for Clostridium Difficile Infection: an Assessment of Antimicrobial Activity Using Conventional Susceptibility Testing and an in Vitro Gut Model." The Journal of Antimicrobial Chemotherapy, vol. 70, no. 1, 2015, pp. 182-9.
Baines SD, Crowther GS, Freeman J, et al. SMT19969 as a treatment for Clostridium difficile infection: an assessment of antimicrobial activity using conventional susceptibility testing and an in vitro gut model. J Antimicrob Chemother. 2015;70(1):182-9.
Baines, S. D., Crowther, G. S., Freeman, J., Todhunter, S., Vickers, R., & Wilcox, M. H. (2015). SMT19969 as a treatment for Clostridium difficile infection: an assessment of antimicrobial activity using conventional susceptibility testing and an in vitro gut model. The Journal of Antimicrobial Chemotherapy, 70(1), 182-9. https://doi.org/10.1093/jac/dku324
Baines SD, et al. SMT19969 as a Treatment for Clostridium Difficile Infection: an Assessment of Antimicrobial Activity Using Conventional Susceptibility Testing and an in Vitro Gut Model. J Antimicrob Chemother. 2015;70(1):182-9. PubMed PMID: 25190720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SMT19969 as a treatment for Clostridium difficile infection: an assessment of antimicrobial activity using conventional susceptibility testing and an in vitro gut model. AU - Baines,S D, AU - Crowther,G S, AU - Freeman,J, AU - Todhunter,S, AU - Vickers,R, AU - Wilcox,M H, Y1 - 2014/09/03/ PY - 2014/9/6/entrez PY - 2014/9/6/pubmed PY - 2015/8/11/medline KW - Clostridium difficile KW - NAP1/027 KW - antibiotics KW - cytotoxin KW - gut model KW - microflora SP - 182 EP - 9 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 70 IS - 1 N2 - OBJECTIVES: We investigated the efficacy of the novel antimicrobial agent SMT19969 in treating simulated Clostridium difficile infection using an in vitro human gut model. METHODS: Concentrations of the predominant cultivable members of the indigenous gut microfloras and C. difficile (total and spore counts) were determined by viable counting. Cytotoxin titres were determined using cell cytotoxicity and expressed as log10 relative units (RU). Clindamycin was used to induce simulated C. difficile PCR ribotype 027 infection. Once high-level cytotoxin titres (≥ 4 RU) were observed, SMT19969 was instilled for 7 days. Two SMT19969 dosing regimens (31.25 and 62.5 mg/L four times daily) were evaluated simultaneously in separate experiments. MICs of SMT19969 were determined against 30 genotypically distinct C. difficile ribotypes. RESULTS: SMT19969 was 7- and 17-fold more active against C. difficile than metronidazole and vancomycin, respectively, against a panel of genotypically distinct isolates (P < 0.05). Both SMT19969 dosing regimens demonstrated little antimicrobial activity against indigenous gut microflora groups except clostridia. SMT19969 inhibited C. difficile growth and repressed C. difficile cytotoxin titres in the gut model. CONCLUSIONS: These data suggest that SMT19969 is a narrow-spectrum and potent antimicrobial agent against C. difficile. Additional studies evaluating SMT19969 in other models of C. difficile infection are warranted, with human studies to place these gut model observations in context. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/25190720/SMT19969_as_a_treatment_for_Clostridium_difficile_infection:_an_assessment_of_antimicrobial_activity_using_conventional_susceptibility_testing_and_an_in_vitro_gut_model_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dku324 DB - PRIME DP - Unbound Medicine ER -