Heteroresistance to rifampicin & isoniazid in clinical samples of patients with presumptive drug-resistant tuberculosis

Abstract

Background
Tuberculosis (TB) remains a significant global health challenge, particularly with the rise of drug-resistant strains. Heteroresistance, where subpopulations of bacteria show varying levels
of resistance within the same patient, complicates diagnosis and treatment. This study aims to
assess the prevalence of heteroresistance to rifampicin and isoniazid in clinical samples from
patients with presumptive drug-resistant tuberculosis.
Materials and Methods
A cross-sectional study was conducted from January to June 2024 at a tertiary care hospital. Clinical samples, including sputum and bronchial lavage, were collected from 200 patients
suspected of having drug-resistant TB. Samples were processed using the GeneXpert MTB/RIF
assay and Löwenstein-Jensen culture for drug susceptibility testing. Isolates were tested for
heteroresistance to rifampicin and isoniazid using the BACTEC MGIT 960 system and
molecular techniques like whole-genome sequencing.
Results
Out of 200 samples, 150 (75%) were confirmed to have Mycobacterium tuberculosis complex.
Among these, 60 samples (40%) exhibited heteroresistance to rifampicin, while 45 samples (30%) showed heteroresistance to isoniazid. Dual heteroresistance to both drugs was observed in 20 samples (13.3%). Whole-genome sequencing revealed mutations in the rpoB and katG genes associated with resistance. The presence of heteroresistant populations was associated with prior TB treatment history and poor treatment outcomes.
Conclusion
The study highlights a substantial prevalence of heteroresistance to rifampicin and isoniazid in
patients with presumptive drug-resistant TB. This underscores the need for advanced diagnostic techniques to detect heteroresistant strains and guide effective treatment regimens. Tailored therapeutic strategies are crucial to managing and controlling the spread of drug resistant TB.