Exposure of drug-resistant tuberculosis drugs in breast milk

Mkhize, Buyisile

Exposure of drug-resistant tuberculosis drugs in breast milk

Thesis / Dissertation

2026

Publisher

University of Cape Town

Department

Department of Medicine

Faculty

Faculty of Health Sciences

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.

Keywords

tuberculosis

breast milk

Reference:

Collections

PhD / Doctoral

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