Drug-resistant tuberculosis and pulmonary co-infections in immunocompromised patients: from multi-omics to precision therapy
Abstract
Drug-resistant tuberculosis remains a major global health threat, with an estimated 400,000 people developing rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) worldwide in 2023, according to the WHO Global Tuberculosis Report 2024. Immunocompromised populations, including people living with HIV, transplant recipients, patients receiving immunosuppressive therapies, and individuals with chronic metabolic diseases, are at particularly high risk of severe disease and pulmonary co-infections, resulting in delayed diagnosis, increased treatment complexity, and poor clinical outcomes. Despite advances in therapeutics, management remains constrained by fragmented diagnostic pathways, limited pathogen resolution, antimicrobial toxicity, and clinically significant drug-drug interactions. Recent progress in multi-omics technologies is reshaping understanding of host-pathogen dynamics in tuberculosis and co-infection states. Whole-genome sequencing enables rapid resistance prediction and transmission tracking, whereas transcriptomic, proteomic, metabolomic, and single-cell approaches are identifying biomarkers of disease severity, immune dysregulation, treatment response, and relapse risk. Parallel advances in metagenomic diagnostics and artificial intelligence-assisted imaging offer opportunities for earlier detection of mixed infections and improved clinical triage. Therapeutic paradigms are also evolving. Shorter all-oral regimens, individualized dosing strategies,…
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