The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro

Show simple item record

dc.contributor.advisor Stoltz, Anton Carel
dc.contributor.coadvisor Nardell, Edward Anthony
dc.contributor.coadvisor Apostolides, Zeno
dc.contributor.postgraduate Van Breda, Shane Vontelin
dc.date.accessioned 2016-01-26T06:28:36Z
dc.date.available 2016-01-26T06:28:36Z
dc.date.created 2016-04-22
dc.date.issued 2016 en_ZA
dc.description Thesis (PhD)--University of Pretoria, 2016. en_ZA
dc.description.abstract Polymyxins have previously been described to have activity against M. tuberculosis (M. tb), 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. Reported here for the first time are the MIC and MBC data for CMS, CST and PST determined by the microtiter Alamar Blue® assay (MABA) against H37Ra and multi-drug-resistant (MDR) M. tb. Additionally determined is how the MIC of CMS 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 M. tb was also determined. MICs for CMS, CST and PST were determined to be too high for systemic use. CMS can, however, be administered by inhalation allowing for high local concentrations with reduced systemic toxicity. The MIC for CMS was antagonised eight fold in PS. For synergy, indifference was determined for both H37Ra and MDR M. tb. Time-kill assays revealed a bactericidal killing effect when CMS was used together with INH against H37Ra M. tb while no enhanced effect of CMS with INH or RIF was observed against MDR M. tb. The resistant effects caused by rpoB and katG mutations could not be overcome. With regard to H37Ra M. tb, ultrastructure analysis suggests that the disruption of the capsule layer (CL) and cytoplasmic membrane (CM) by CMS may enhance the uptake of INH. These findings may provide insight for further investigations of CMS against M. tb. en_ZA
dc.description.availability Unrestricted en_ZA
dc.description.department Medical Microbiology en_ZA
dc.identifier.citation Van Breda, SV 2012, The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro. PhD thesis, University of Pretoria, Pretoria, yymmdd <http://hdl.handle.net/2263/51262> en_ZA
dc.identifier.other A2016
dc.identifier.uri http://hdl.handle.net/2263/51262
dc.language.iso en en_ZA
dc.publisher University of Pretoria en_ZA
dc.rights © 2016 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. en_ZA
dc.subject Internal Medicine en_ZA
dc.subject UCTD
dc.subject Infectious Diseases
dc.title The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro en_ZA
dc.type Thesis en_ZA


Files in this item

This item appears in the following Collection(s)

Show simple item record