Host, pathogen, lesion, and pharmacological determinants of tuberculosis treatment outcomes: toward precision therapy—a narrative review

Tuberculosis (TB) remains a major global health challenge despite the availability of effective antimicrobial therapy and standardized multidrug treatment regimens. Although current treatment approaches achieve favorable outcomes in many patients, considerable variability in treatment response, bacterial clearance, relapse, and treatment failure persists. Such variability cannot be explained solely by drug efficacy and instead reflects the complex biological environment in which anti-tuberculosis therapy operates. Treatment outcomes are influenced by multiple interconnected determinants, including host-related factors, pharmacological variability, lesion heterogeneity, and pathogen-specific characteristics. Host factors such as immune status, diabetes, HIV infection, and malnutrition can significantly alter disease progression and therapeutic response. Pharmacokinetic variability may result in substantial differences in systemic and tissue drug exposure among patients receiving similar guideline-based treatment regimens. At the site of infection, heterogeneous lesion microenvironments influence drug penetration and bacterial survival, while pathogen-related factors, including bacterial burden, persistence, drug tolerance, and antimicrobial resistance, further contribute to variability in treatment outcomes. Understanding the interplay among host, pathogen, lesion, and pharmacological factors provides important opportunities for improving treatment precision and therapeutic effectiveness. This review examines the major determinants influencing tuberculosis treatment outcomes and discusses emerging precision-therapy strategies, including therapeutic drug monitoring, patient stratification, lesion-informed treatment approaches, and host-directed interventions. Recognizing and addressing biological variability may represent an important step toward more individualized and effective tuberculosis management.