Interactions of linezolid and second-line anti-TB agents against multidrug-resistant Mycobacterium tuberculosis in vitro and in vivo.

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Interactions of linezolid and second-line anti-TB agents against multidrug-resistant Mycobacterium tuberculosis in vitro and in vivo.

Int J Infect Dis. 2016 Sep 6;

Authors: Zhao W, Zheng M, Wang B, Mu X, Li P, Fu L, Liu S, Guo Z

Abstract
OBJECTIVES: (i) To evaluate the interactions between linezolid (LZD) and second-line anti-TB agents against susceptible and multidrug-resistant tuberculosis in vitro. (ii) To validate the in vitro results in tuberculosis murine model.
METHODS: The MICs of LZD and 7 second-line anti-TB drugs against H37Rv and 3 multidrug-resistant clinical isolates were determined by Alamar Blue assay, and the interaction patterns of LZD and the 7 second-line anti-TB agents against 4 isolates were studied using a dynamic checkerboard method. The activities of these combinations against M. tuberculosis were evaluated in a murine model of tuberculosis.
RESULTS: The combination of LZD+capreomycin exhibited partial synergism in 3 of 4 isolates, LZD+para-aminosalisylic acid exhibited partial synergismdid in 2 of 4 isolates, and LZD+Levofloxacin and LZD+Amikacin exhibited partial synergism in 1 of 4 isolates, whereas all other combinations showed indifference or additive in vitro. The activities of 6 combinations and the standard regimen Rifampicin+Isoniazid+Pyraziamid were investigated in a murine model of tuberculosis infected with H37Rv. Significant CFU reductions were found in LZD+CPM and LZD+CFZ groups when the CFU in the lungs were compared on D0 (the day of beginning treatment) and after 2 months of treatment.
CONCLUSIONS: These combinations of LZD and second-line anti-TB drugs were all active against MDR-TB with indifference or additive effect, except LZD+CPM, which showed partial synergy.

PMID: 27613365 [PubMed - as supplied by publisher]