Prevalence of sub-optimal drug levels of Rifampicin, Isoniazid and Pyrazinamide among tuberculosis patients in Sydney, Australia. A pilot study.

<b>Background:</b> Despite its potential utility, therapeutic drug monitoring (TDM) for Mycobacterium tuberculosis (TB) is not available in many settings including New South Wales (NSW). <b>Objectives:</b> Establish a TDM assay for clinical use amongst drug susceptible-TB patients in Sydney and evaluate its acceptance and utility in identifying sub-optimal drug levels. <b>Methods:</b> All adult patients with newly diagnosed microbiologically-confirmed pulmonary TB at St Vincent’s Hospital between January 2020 and May 2020 were eligible. Serum was collected before TB medications and again at 1, 3 and 6 hours. Collection was repeated at weeks 2, 4 and 6. Patients completed standardised questionnaires at each visit. Quantitative TDM was performed via liquid-chromatography tandem-mass spectrometry. Drug exposure (area under concentration time curve) was calculated and related to clinical outcomes and published reference ranges for each TB medication. <b>Results:</b> Of 23 new TB patients, 22 (96%) consented to the study with 2 withdrawals (personal reasons) and a median age of 31.5 years. Disinterest and fear of needles was cited by the singular non-participant. 96% of study patients attended all scheduled sample collections. Cmax levels below the published reference range were found for rifampicin; 16% (3/19), isoniazid; 41% (7/17) and pyrazinamide; 10% (2/20) ranges across all sampling sessions. <b>Conclusions:</b> TDM appears to be well accepted among patients and reveals lower than expected levels of TB medications particularly for Isoniazid. This raises potential concerns about acquired drug resistance and treatment failure.