Beyond the pill count: unmasking the pharmacokinetic drivers of recurrent tuberculosis

A young adult female presented with recurrent sputum smear-positive pulmonary tuberculosis (TB) despite completing four prior courses of standard first-line anti-tubercular therapy. She presented with progressive breathlessness, productive cough and intermittent fever. Imaging revealed bilateral upper lobe fibrocavitary disease with cystic bronchiectasis. Repeated molecular testing confirmed Mycobacterium tuberculosis without rifampicin or isoniazid resistance. Therapeutic drug monitoring (TDM), though not routinely recommended in TB management, was undertaken in view of recurrent disease and showed undetectable rifampicin and subtherapeutic isoniazid concentrations, pointing towards impaired absorption or altered pharmacokinetics as the likely cause of recurrence. The patient was treated with a higher-dose fixed-dose combination regimen supplemented with pyridoxine, probiotics, vitamin D and nutritional support. After 6 months, she showed symptomatic improvement, weight gain, sputum conversion and reduced respiratory symptoms. This case emphasises the importance of identifying alternative causes of recurrence and supports the role of TDM in patients with recurrent drug-sensitive TB.