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Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis
Dissertation (MSc)--University of Pretoria, 2020.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2020
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| _version_ | 1867613498978074625 |
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| access_status_str | Open Access |
| author2 | Cholo, Moloko C. |
| author_browse | Cholo, Moloko C. |
| author_facet | Cholo, Moloko C. |
| collection | Thesis |
| dc_rights_str_mv | © 2019 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 | Dissertation (MSc)--University of Pretoria, 2020. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/75502 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:06.816Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| 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:2263/75502 Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis Cholo, Moloko C. mashelesa2@gmail.com Steel, Helen Carolyn Mashele, Sizeka Aubrey UCTD Tuberculosis (TB) Clofazimine (CFZ) Antimycobacterial Mycobacterium tuberculosis Antitubercular drugs Drug combinations Inhibitory activity Bactericidal activity Minimum inhibitory concentration (MIC) Minimum bactericidal concentration (MBC) Fractional inhibitory concentration index (FICI) Microbial cultures Planktonic cultures Biofilm-forming cultures Synergistic effects Treatment outcome Antimicrobial resistance TB chemotherapy Public health Drug development Drug efficacy TB treatment Health sciences theses SDG-03 SDG-03: Good health and well-being Health sciences theses SDG-17 SDG-17: Partnerships for the goals Dissertation (MSc)--University of Pretoria, 2020. This thesis/dissertation is under embargo or restricted until September 2022. BACKGROUND : The chemotherapy of tuberculosis (TB) patients is administered for a six to nine-month period consisting of an intensive phase during the first two months with four primary anti-TB drugs, rifampicin (RMP), isoniazid (INH), ethambutol (EMB) and pyrazinamide (PZA), followed by a continuation phase during the remaining four to seven months with RMP and INH. During the intensive phase the active-replicating organisms (AR) are effectively and rapidly eliminated (99% killing), while the slow-replicating (SR) / non-replicating (NR) populations are targeted during the continuation phase. These latter bacterial populations respond poorly to treatment and are often associated with disease reactivation and relapse in treated patients, highlighting the necessity of identifying effective antimicrobial agents against these bacteria. Clofazimine (CFZ) has demonstrated high antimycobacterial activities against the AR, SR and NR microbial populations in vitro. However, its effects in combination with the primary drugs against these bacteria have not been demonstrated. AIMS AND OBJECTIVES : To investigate the antimycobacterial activity of CFZ in combination with primary anti-TB drugs against the AR and SR organisms isolated in planktonic and biofilm-forming cultures respectively, by evaluating their inhibitory and bactericidal activities. METHODS : The inhibitory activities of CFZ and three primary anti-TB drugs viz. RMP, INH and EMB were evaluated individually and in combination using minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) determinations by the microtitre Alamar blue assay (MABA) and biofilm formation/ and crystal violet quantification for planktonic and biofilm cultures respectively. The bactericidal activities of these various combinations of the test agents were evaluated using minimum bactericidal concentration (MBC) and fractional bactericidal concentration index (FBCI) determinations by colony-counting procedures. RESULTS : In planktonic cultures, CFZ demonstrated a high inhibitory (MIC: 0.15 μg/mL), but low bactericidal activity (MBC: 5 μg/mL). In combination with primary anti-TB drugs, CFZ demonstrated synergistic inhibitory activities in combination with RMP and INH individually, as well as when the two antibiotics were used together. With respect to bactericidal activity, CFZ exhibited synergistic activity only in a two-drug combination with RMP. Synergistic activities were also demonstrated in a two-drug combination of RIF and INH and in a three-drug combination of these two antibiotics with EMB. However, in biofilm-forming cultures, CFZ demonstrated high inhibitory and bactericidal activities, achieving equal MIC and MBC values of 0.15 μg/mL. All CFZ-containing anti-TB drug combinations exhibited synergistic effects, with high activities being shown in combinations containing RIF and INH. CONCLUSION : CFZ exhibited synergistic effects in combination with primary anti-TB drugs against both planktonic and biofilm-forming cultures, showing potential benefit in promoting treatment outcome when used in TB chemotherapy. em2025 Immunology MSc Unrestricted SDG-03: Good health and well-being SDG-17: Partnerships for the goals 2020-07-30T10:13:36Z 2020-07-30T10:13:36Z 2020 2020 Dissertation Mashele, SA 2020, Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/75502> S2020 http://hdl.handle.net/2263/75502 en © 2019 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 University of Pretoria |
| spellingShingle | UCTD Tuberculosis (TB) Clofazimine (CFZ) Antimycobacterial Mycobacterium tuberculosis Antitubercular drugs Drug combinations Inhibitory activity Bactericidal activity Minimum inhibitory concentration (MIC) Minimum bactericidal concentration (MBC) Fractional inhibitory concentration index (FICI) Microbial cultures Planktonic cultures Biofilm-forming cultures Synergistic effects Treatment outcome Antimicrobial resistance TB chemotherapy Public health Drug development Drug efficacy TB treatment Health sciences theses SDG-03 SDG-03: Good health and well-being Health sciences theses SDG-17 SDG-17: Partnerships for the goals Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis |
| title | Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis |
| title_full | Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis |
| title_fullStr | Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis |
| title_full_unstemmed | Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis |
| title_short | Optimising the efficacy of clofazimine against biofilm-encased Mycobacterium tuberculosis |
| title_sort | optimising the efficacy of clofazimine against biofilm encased mycobacterium tuberculosis |
| topic | UCTD Tuberculosis (TB) Clofazimine (CFZ) Antimycobacterial Mycobacterium tuberculosis Antitubercular drugs Drug combinations Inhibitory activity Bactericidal activity Minimum inhibitory concentration (MIC) Minimum bactericidal concentration (MBC) Fractional inhibitory concentration index (FICI) Microbial cultures Planktonic cultures Biofilm-forming cultures Synergistic effects Treatment outcome Antimicrobial resistance TB chemotherapy Public health Drug development Drug efficacy TB treatment Health sciences theses SDG-03 SDG-03: Good health and well-being Health sciences theses SDG-17 SDG-17: Partnerships for the goals |
| url | http://hdl.handle.net/2263/75502 |