Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice.
- Author:
Zhen Yong GUO
1
;
Wei Jie ZHAO
1
;
Mei Qin ZHENG
1
;
Shuo LIU
1
;
Chen Xia YAN
1
;
Peng LI
1
;
Shao Fa XU
1
Author Information
- Publication Type:Journal Article
- Keywords: Activity; Biapenem; Clavulanate; Extensive drug-resistant; Macrophage; Multidrug resistant; Mycobacterium tuberculosis; Synergy
- MeSH: Animals; Anti-Infective Agents; pharmacology; therapeutic use; Cell Line; Drug Evaluation, Preclinical; Macrophages; Mice; Mycobacterium tuberculosis; drug effects; Thienamycins; pharmacology; therapeutic use; Tuberculosis, Multidrug-Resistant; drug therapy
- From: Biomedical and Environmental Sciences 2019;32(4):235-241
- CountryChina
- Language:English
-
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.
