Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea

ABSTRACT: Objectives: Antibiotics are associated with increased risk of Clostridioides difficile infection, which has limited treatment options. We assessed in vitro activity of omadacycline (an aminomethylcycline antibiotic) against the C. difficile infection strain and efficacy in a hamster model...

Full description

Bibliographic Details
Main Authors: Raina Gay Leahy, Alisa W. Serio, Kelly Wright, Maria M. Traczewski, S. Ken Tanaka
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:Journal of Global Antimicrobial Resistance
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213716522000960
_version_ 1798003240450654208
author Raina Gay Leahy
Alisa W. Serio
Kelly Wright
Maria M. Traczewski
S. Ken Tanaka
author_facet Raina Gay Leahy
Alisa W. Serio
Kelly Wright
Maria M. Traczewski
S. Ken Tanaka
author_sort Raina Gay Leahy
collection DOAJ
description ABSTRACT: Objectives: Antibiotics are associated with increased risk of Clostridioides difficile infection, which has limited treatment options. We assessed in vitro activity of omadacycline (an aminomethylcycline antibiotic) against the C. difficile infection strain and efficacy in a hamster model of C. difficile-associated diarrhoea. Methods: Omadacycline, clindamycin, tigecycline, vancomycin, and metronidazole minimum inhibitory concentrations (MICs) for the infection-model strain (C. difficile ATCC 43596) were determined. Hamsters were pretreated with subcutaneous clindamycin (10 mg/kg) and infected 24 h later with C. difficile ATCC 43596; 24 h post infection, they received oral omadacycline (50 mg/kg/day), vancomycin (50 mg/kg/day), or vehicle for 5 days. Efficacy was reported as survival. Results: Omadacycline was as active as tigecycline, vancomycin, and metronidazole (MIC 0.06 mg/L); clindamycin showed no activity. Median survival in hamsters was: 12 days, omadacycline; 2 days, vancomycin; 4 days, clindamycin pretreatment only. Conclusion: Omadacycline exhibited potent in vitro activity against C. difficile and showed efficacy in a model of C. difficile-associated diarrhoea.
first_indexed 2024-04-11T12:05:50Z
format Article
id doaj.art-061fc20000c14acfb1c1d713fad6c482
institution Directory Open Access Journal
issn 2213-7165
language English
last_indexed 2024-04-11T12:05:50Z
publishDate 2022-09-01
publisher Elsevier
record_format Article
series Journal of Global Antimicrobial Resistance
spelling doaj.art-061fc20000c14acfb1c1d713fad6c4822022-12-22T04:24:44ZengElsevierJournal of Global Antimicrobial Resistance2213-71652022-09-01309699Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoeaRaina Gay Leahy0Alisa W. Serio1Kelly Wright2Maria M. Traczewski3S. Ken Tanaka4Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USAParatek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA; Corresponding author. 1000 First Avenue, Suite 200, King of Prussia, PA 19406, USA.Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USAClinical Microbiology Institute, Inc., Wilsonville, Oregon, USAParatek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USAABSTRACT: Objectives: Antibiotics are associated with increased risk of Clostridioides difficile infection, which has limited treatment options. We assessed in vitro activity of omadacycline (an aminomethylcycline antibiotic) against the C. difficile infection strain and efficacy in a hamster model of C. difficile-associated diarrhoea. Methods: Omadacycline, clindamycin, tigecycline, vancomycin, and metronidazole minimum inhibitory concentrations (MICs) for the infection-model strain (C. difficile ATCC 43596) were determined. Hamsters were pretreated with subcutaneous clindamycin (10 mg/kg) and infected 24 h later with C. difficile ATCC 43596; 24 h post infection, they received oral omadacycline (50 mg/kg/day), vancomycin (50 mg/kg/day), or vehicle for 5 days. Efficacy was reported as survival. Results: Omadacycline was as active as tigecycline, vancomycin, and metronidazole (MIC 0.06 mg/L); clindamycin showed no activity. Median survival in hamsters was: 12 days, omadacycline; 2 days, vancomycin; 4 days, clindamycin pretreatment only. Conclusion: Omadacycline exhibited potent in vitro activity against C. difficile and showed efficacy in a model of C. difficile-associated diarrhoea.http://www.sciencedirect.com/science/article/pii/S2213716522000960Clostridioides difficileClostridium difficileOmadacyclineHamster modelSurvivalMinimum inhibitory concentration
spellingShingle Raina Gay Leahy
Alisa W. Serio
Kelly Wright
Maria M. Traczewski
S. Ken Tanaka
Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea
Journal of Global Antimicrobial Resistance
Clostridioides difficile
Clostridium difficile
Omadacycline
Hamster model
Survival
Minimum inhibitory concentration
title Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea
title_full Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea
title_fullStr Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea
title_full_unstemmed Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea
title_short Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea
title_sort activity of omadacycline in vitro against clostridioides difficile and preliminary efficacy assessment in a hamster model of c difficile associated diarrhoea
topic Clostridioides difficile
Clostridium difficile
Omadacycline
Hamster model
Survival
Minimum inhibitory concentration
url http://www.sciencedirect.com/science/article/pii/S2213716522000960
work_keys_str_mv AT rainagayleahy activityofomadacyclineinvitroagainstclostridioidesdifficileandpreliminaryefficacyassessmentinahamstermodelofcdifficileassociateddiarrhoea
AT alisawserio activityofomadacyclineinvitroagainstclostridioidesdifficileandpreliminaryefficacyassessmentinahamstermodelofcdifficileassociateddiarrhoea
AT kellywright activityofomadacyclineinvitroagainstclostridioidesdifficileandpreliminaryefficacyassessmentinahamstermodelofcdifficileassociateddiarrhoea
AT mariamtraczewski activityofomadacyclineinvitroagainstclostridioidesdifficileandpreliminaryefficacyassessmentinahamstermodelofcdifficileassociateddiarrhoea
AT skentanaka activityofomadacyclineinvitroagainstclostridioidesdifficileandpreliminaryefficacyassessmentinahamstermodelofcdifficileassociateddiarrhoea