Interaction between linezolid and Mycobacterium tuberculosis in an experimental in vitro model

As linezolid is emerging as a useful alternative in the treatment of multi-resistant tuberculosis, we developed an in vitro model to elucidate certain aspects of the interaction that takes place between the microorganism and the antibiotic. We found that the drug does not generate resistant mutants following repeated exposure at subinhibitory concentrations and that it exhibits bactericidal activity against most of the susceptible strains in vitro at high concentrations (83.3% of the strains at concentrations of 50 μg/mL) in the exponential growth phase. This bactericidal activity is much less if the microorganism is in nonreplicating phase, even in the case of susceptible strains in vitro. Therefore, linezolid appears to be an alternative as far as generation of resistance is concerned in the treatment of multi-resistant tuberculosis. However, it has limited bactericidal capacity against strains in nonreplicant phase, which makes it necessary to use linezolid in combination with other drugs that act on these microorganisms.