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
de En
| WPRIM
| ID: wpr-773400
Bibliothèque responsable:
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.
Mots clés
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Pharmacologie
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Lignée cellulaire
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Thiénamycine
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Tuberculose multirésistante
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Utilisations thérapeutiques
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Évaluation préclinique de médicament
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Traitement médicamenteux
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Macrophages
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Anti-infectieux
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Mycobacterium tuberculosis
Limites du sujet:
Animals
langue:
En
Texte intégral:
Biomedical and Environmental Sciences
Année:
2019
Type:
Article