Personalized Tuberculosis Care for Drug-Resistant Tuberculosis

Drug-resistant tuberculosis (DR-TB) includes mono-resistant forms of TB and multidrug-resistant tuberculosis (MDR-TB), defined by loss of susceptibility to Rifampicin and Isoniazid. MDR-TB is subdivided along a gradient of further loss of susceptibility, with extensively drug-resistant tuberculosis (XDR-TB) characterized by resistance to any fluoroquinolones and Linezolid or Bedaquiline. Even XDR-TB is far from homogeneous, and neither are patient groups affected by these different forms of DR-TB, with co-infections and comorbidities, differences in genetic background, disease severity, nutritional status, gender, and body composition. Drug exposure relative to minimal inhibitory concentrations for each regimen drug, including core- and companion drugs, determines the outcome. Inter- and intra-individual drug exposure are highly variable; therapeutic drug monitoring (TDM) by measuring drug exposure in multiple blood samples following drug administration is helpful in fine-tuning treatment. Apart from TB drugs, patients may benefit from host-directed therapies, including therapeutic vaccinations and surgical interventions. TDM is still under development, but appropriate technologies have been developed to apply TDM even in low-resource settings.