Exposure of drug-resistant tuberculosis drugs in breast milk
| dc.contributor.advisor | Wiesner, Lubbe | |
| dc.contributor.advisor | Court, Richard | |
| dc.contributor.advisor | Castel, Sandra | |
| dc.contributor.advisor | Joubert, Anton | |
| dc.contributor.author | Mkhize, Buyisile | |
| dc.date.accessioned | 2026-09-23T12:01:06Z | |
| dc.date.available | 2026-09-23T12:01:06Z | |
| dc.date.issued | 2026 | |
| dc.date.updated | 2026-09-23T12:00:14Z | |
| dc.description.abstract | Resistance of Mycobacterium tuberculosis to therapeutic drugs is a growing concern. Therefore, it is essential to evaluate the presence and concentration of these drugs in breast milk, as this provides crucial insight into potential infant exposure during breastfeeding. Novel analytical methods for the analysis of major second-line anti-tuberculosis drugs bedaquiline and delamanid (and their metabolites), and a multiplex method for the analysis of clofazimine, linezolid, levofloxacin, and moxifloxacin in breast milk, were developed and validated according to the guidelines of the USA Food and Drug Administration and the European Medicines Agency. The analytes were extracted by protein precipitation combined with off-line or on-line solid phase extraction and quantified using liquid chromatography with mass spectrometry. The methods were shown to be sensitive, accurate, reproducible, and robust, ensuring reliable measurements of all the drugs in breast milk. The validated methods successfully measured drug concentrations in breast milk samples of participants with drug-resistant tuberculosis in the BEAT-Tuberculosis and King Dinizulu Hospital studies in South Africa. Validated analytical methods were used to analyse the drugs in plasma samples taken in parallel to the breast milk samples, allowing for a comparison of drug concentrations between plasma and breast milk. Higher drug concentrations in breast milk than in plasma were observed for most tuberculosis drugs analysed, suggesting a notable potential for drug transfer to breastfed infants. This dual analysis supports a deeper understanding of drug distribution and exposure in breastfeeding mothers and their infants. The findings highlight the need for further research into the pharmacokinetics of anti-tuberculosis drugs in breastfed infants to establish potential health impacts and identify safety concerns. Such knowledge will allow for the adjustment of treatment protocols for breastfeeding mothers to achieve effective multidrug-resistant/extensively drug-resistant tuberculosis treatment while ensuring the safety of breastfed infants. | |
| dc.identifier.apacitation | Mkhize, B. (2026). <i>Exposure of drug-resistant tuberculosis drugs in breast milk</i>. (). University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/43804 | en_ZA |
| dc.identifier.chicagocitation | Mkhize, Buyisile. <i>"Exposure of drug-resistant tuberculosis drugs in breast milk."</i> ., University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2026. http://hdl.handle.net/11427/43804 | en_ZA |
| dc.identifier.citation | Mkhize, B. 2026. Exposure of drug-resistant tuberculosis drugs in breast milk. . University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. http://hdl.handle.net/11427/43804 | en_ZA |
| dc.identifier.ris | TY - Thesis / Dissertation AU - Mkhize, Buyisile AB - Resistance of Mycobacterium tuberculosis to therapeutic drugs is a growing concern. Therefore, it is essential to evaluate the presence and concentration of these drugs in breast milk, as this provides crucial insight into potential infant exposure during breastfeeding. Novel analytical methods for the analysis of major second-line anti-tuberculosis drugs bedaquiline and delamanid (and their metabolites), and a multiplex method for the analysis of clofazimine, linezolid, levofloxacin, and moxifloxacin in breast milk, were developed and validated according to the guidelines of the USA Food and Drug Administration and the European Medicines Agency. The analytes were extracted by protein precipitation combined with off-line or on-line solid phase extraction and quantified using liquid chromatography with mass spectrometry. The methods were shown to be sensitive, accurate, reproducible, and robust, ensuring reliable measurements of all the drugs in breast milk. The validated methods successfully measured drug concentrations in breast milk samples of participants with drug-resistant tuberculosis in the BEAT-Tuberculosis and King Dinizulu Hospital studies in South Africa. Validated analytical methods were used to analyse the drugs in plasma samples taken in parallel to the breast milk samples, allowing for a comparison of drug concentrations between plasma and breast milk. Higher drug concentrations in breast milk than in plasma were observed for most tuberculosis drugs analysed, suggesting a notable potential for drug transfer to breastfed infants. This dual analysis supports a deeper understanding of drug distribution and exposure in breastfeeding mothers and their infants. The findings highlight the need for further research into the pharmacokinetics of anti-tuberculosis drugs in breastfed infants to establish potential health impacts and identify safety concerns. Such knowledge will allow for the adjustment of treatment protocols for breastfeeding mothers to achieve effective multidrug-resistant/extensively drug-resistant tuberculosis treatment while ensuring the safety of breastfed infants. DA - 2026 DB - OpenUCT DP - University of Cape Town KW - tuberculosis KW - breast milk LK - https://open.uct.ac.za PB - University of Cape Town PY - 2026 T1 - Exposure of drug-resistant tuberculosis drugs in breast milk TI - Exposure of drug-resistant tuberculosis drugs in breast milk UR - http://hdl.handle.net/11427/43804 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/43804 | |
| dc.identifier.vancouvercitation | Mkhize B. Exposure of drug-resistant tuberculosis drugs in breast milk. []. University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2026 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/43804 | en_ZA |
| dc.language.iso | en | |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Medicine | |
| dc.publisher.faculty | Faculty of Health Sciences | |
| dc.publisher.institution | University of Cape Town | |
| dc.subject | tuberculosis | |
| dc.subject | breast milk | |
| dc.title | Exposure of drug-resistant tuberculosis drugs in breast milk | |
| dc.type | Thesis / Dissertation | |
| dc.type.qualificationlevel | Doctoral | |
| dc.type.qualificationlevel | PhD |