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The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro
Thesis (PhD)--University of Pretoria, 2016.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2016
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| _version_ | 1867613610346283008 |
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| access_status_str | Open Access |
| author2 | Stoltz, Anton Carel |
| author_browse | Stoltz, Anton Carel |
| author_facet | Stoltz, Anton Carel |
| collection | Thesis |
| dc_rights_str_mv | © 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. |
| description | Thesis (PhD)--University of Pretoria, 2016. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/51262 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:38:53.005Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/51262 The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro Stoltz, Anton Carel Nardell, Edward Anthony Apostolides, Zeno Van Breda, Shane Vontelin Internal Medicine UCTD Infectious Diseases Drug safety Antagonism Drug efficacy Tuberculosis treatment Antibiotic synergy Health sciences theses SDG-03 SDG-03: Good health and well-being Health sciences theses SDG-09 SDG-09: Industry, innovation and infrastructure Health sciences theses SDG-17 SDG-17: Partnerships for the goals Thesis (PhD)--University of Pretoria, 2016. 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. em2025 Medical Microbiology Unrestricted SDG-03: Good health and well-being SDG-09: Industry, innovation and infrastructure SDG-17: Partnerships for the goals 2016-01-26T06:28:36Z 2016-01-26T06:28:36Z 2016-04-22 2016 Thesis 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> A2016 http://hdl.handle.net/2263/51262 en © 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. application/pdf application/pdf application/pdf University of Pretoria |
| spellingShingle | Internal Medicine UCTD Infectious Diseases Drug safety Antagonism Drug efficacy Tuberculosis treatment Antibiotic synergy Health sciences theses SDG-03 SDG-03: Good health and well-being Health sciences theses SDG-09 SDG-09: Industry, innovation and infrastructure Health sciences theses SDG-17 SDG-17: Partnerships for the goals The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro |
| title | The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro |
| title_full | The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro |
| title_fullStr | The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro |
| title_full_unstemmed | The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro |
| title_short | The antimicrobial effect of colistin methanesulfonate (polymyxin E) on Mycobacterium tuberculosis in vitro |
| title_sort | antimicrobial effect of colistin methanesulfonate polymyxin e on mycobacterium tuberculosis in vitro |
| topic | Internal Medicine UCTD Infectious Diseases Drug safety Antagonism Drug efficacy Tuberculosis treatment Antibiotic synergy Health sciences theses SDG-03 SDG-03: Good health and well-being Health sciences theses SDG-09 SDG-09: Industry, innovation and infrastructure Health sciences theses SDG-17 SDG-17: Partnerships for the goals |
| url | http://hdl.handle.net/2263/51262 |