Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice / 生物医学与环境科学(英文)
Biomedical and Environmental Sciences
; (12): 235-241, 2019.
Article
in En
| WPRIM
| ID: wpr-773400
Responsible library:
WPRO
ABSTRACT
OBJECTIVE@#To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.@*METHODS@#Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice..@*RESULTS@#BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment.@*CONCLUSION@#BP/CL may provide a new option to clinically treat MDR tuberculosis.
Key words
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Index:
WPRIM
Main subject:
Pharmacology
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Cell Line
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Thienamycins
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Tuberculosis, Multidrug-Resistant
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Therapeutic Uses
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Drug Evaluation, Preclinical
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Drug Therapy
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Macrophages
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Anti-Infective Agents
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Mycobacterium tuberculosis
Limits:
Animals
Language:
En
Journal:
Biomedical and Environmental Sciences
Year:
2019
Type:
Article