In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 61, No. 5 ( 2017-05)
Abstract:
The in vitro activity and in vivo efficacy of omadacycline (OMC) were evaluated against the causative pathogens of anthrax and plague, Bacillus anthracis and Yersinia pestis , respectively. MICs of OMC were determined by broth microdilution according to CLSI guidelines for 30 isolates each of Y. pestis and B. anthracis . The in vivo efficacy of omadacycline was studied at a range of dosages in both a postexposure prophylaxis (PEP) murine model of anthrax and plague as well as in a delayed treatment model of inhalational anthrax. Omadacycline was active in vitro against Y. pestis (MIC 90 of 1 μg/ml) and B. anthracis (MIC 90 of 0.06 μg/ml). Omadacycline was less active in vitro than ciprofloxacin (CIP) against Y. pestis (CIP MIC 90 of 0.03 μg/ml) but was more potent in vitro against B. anthracis (CIP MIC 90 of 0.12 μg/ml). In the mouse model of infection, the survival curves for all treatment cohorts differed significantly from the vehicle control ( P = 0.004). The median survival for the vehicle-treated controls was 6 days postchallenge, while all antibiotic-treated mice survived the entire study. Omadacycline treatment with 5, 10, or 20 mg/kg of body weight twice daily for 14 days had significant efficacy over the vehicle control in the treatment of aerosolized B. anthracis . Additionally, for postexposure prophylaxis treatment of mice infected with Y. pestis , the survival curves for omadacycline (40 mg/kg twice daily), ciprofloxacin, and doxycycline cohorts differed significantly from the vehicle control ( P 〈 0.0001). Omadacycline is potent and demonstrates efficacy against both B. anthracis and Y. pestis . The well-characterized oral and intravenous pharmacokinetics, safety, and tolerability warrant further assessment of the potential utility of omadacycline in combating these serious biothreat organisms.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.02434-16
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2017
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
