In vitro
and
in vivo
activity of oxazolidinone candidate OTB-658 against
Mycobacterium tuberculosis
In this work, we assess anti-tuberculosis activity of OTB-658 in vitro and in vivo . In vitro , OTB-658 showed bacteriostatic effectiveness with a lower minimum inhibitory concentration than linezolid against Mycobacterium tuberculosis . The minimal bactericidal concentrations and time-kill curves for OTB-658 indicated similar inhibition activity to that of linezolid. OTB-658 entered macrophages to inhibit of M. tuberculosis growth. OTB-658 had a low mutant frequency (10 −8 ), which would prevent drug-resistant mutations from emerging in combination regimens. In vivo , OTB-658 reduced colony-forming unit counts in the lungs and slightly inhibited bacterial growth in the spleen in the early stage and steady state in acute and chronic murine TB models. These results support the preclinical evaluation of OTB-658 and further clinical trials in China.