Abstract:
Polymyxins have previously been described to have activity against M. tuberculosis
(MTB), but further research was abandoned due to systemic toxicity concerns to
achieve the required MIC. Colistin methanesulfonate (CMS), a polymyxin, is well
tolerated when inhaled directly into the lungs, resulting in high local concentrations.
We report here for the first time, MIC and MBC data for CMS determined by the
microtiter Alamar Blue assay (MABA). We also determined how the MIC would be
affected by the presence of pulmonary surfactant (PS) and if any synergy with isoniazid (INH) and rifampicin (RIF) exists. The effect of CMS on the ultrastructure
of MTB was also determined. The MIC for CMS was 16 mg/L, while the MBC was
256 mg/L. MIC for CMS in PS was antagonised by eight fold. For synergy,
indifference was determined while time-kill assays revealed a greater killing effect
when CMS was used together with INH. Ultrastructure analysis suggests that the
disruption of the outer polysaccharide layer of MTB by CMS may lead to enhanced
uptake of INH. Our findings may provide insight for further investigations of CMS
against MTB.
