Managing drug-resistant mycobacterial infections: practical approaches for clinicians

Drug-resistant mycobacterial infections demand coordinated clinical management that integrates diagnostics, pharmacology, and public-health measures. Clinicians should prioritize timely species identification, targeted susceptibility testing, and individualized regimens that account for site of disease, comorbidities, and potential drug interactions. Multidisciplinary input improves outcomes and reduces the risk of further resistance through stewardship and surveillance.

This article is for informational purposes only and should not be considered medical advice. Please consult a qualified healthcare professional for personalized guidance and treatment.

Antibiotics: What factors guide selection?

Antibiotic selection requires knowledge of the mycobacterial species and resistance profile. For pulmonary disease, consider agents with good lung penetration and intracellular activity. Use combination therapy to reduce selective pressure and avoid monotherapy for active infection. Adjust dosing for renal or hepatic dysfunction, and review interactions with rifamycins and other commonly used drugs. Where available, therapeutic drug monitoring can optimize exposure for agents with narrow therapeutic windows.

Diagnostics: Which tests should be prioritized?

Rapid molecular diagnostics accelerate species identification and detect common resistance mutations, informing early treatment choices. Culture and phenotypic susceptibility testing remain important for complex or uncommon resistance patterns and when molecular markers do not fully predict phenotype. High-quality respiratory samples, induced sputum or bronchoscopy for pulmonary cases, and tailored sampling strategies for extrapulmonary disease improve diagnostic yield. Integrating lab results with local surveillance data supports better empiric choices while awaiting definitive results.

Resistance: How to interpret mechanisms and patterns?

Resistance arises from target-site mutations, efflux mechanisms, and enzymatic drug modification. Interpreting genotypic results requires awareness of which mutations confer high-level resistance and which indicate intermediate risk. When resistance to first-line agents is detected, expand testing to second-line drugs and newer agents that may retain activity. Document resistance patterns clearly, and report unexpected profiles to public-health authorities to inform regional surveillance and outbreak response.

Adherence: How can clinicians support sustained treatment?

Sustained adherence is essential to prevent treatment failure and limit further resistance. Use patient-centred strategies: simplify regimens where feasible, provide clear counselling on expected side effects, and engage adherence supports such as community health workers or directly observed therapy in suitable contexts. Address social determinants—medication access, transportation, housing instability—that impede adherence by coordinating with social services. For adolescents and adults, digital adherence tools may supplement conventional approaches; in children, caregiver education and palatable formulations are crucial.

Regimen: How to design effective treatment plans?

Regimen design should be individualized based on susceptibility testing, disease severity, and patient-specific factors including pregnancy and comorbidities. Prefer multidrug regimens with complementary mechanisms and avoid agents with overlapping toxicity when alternatives exist. Define target treatment duration based on site of infection and microbiologic response, and schedule regular monitoring for clinical, radiologic, and laboratory markers of efficacy and toxicity. Engage pharmacy and infectious-disease specialists for regimen optimization and management of complex interactions.

Pediatric and pulmonary: What are the special considerations?

Children often require different diagnostic approaches, dosing strategies, and attention to long-term toxicity risks. Sample collection may need alternative techniques, and dosing must be weight-based with appropriate formulations. Pulmonary disease management emphasizes airway sampling, radiologic follow-up, and interventions to support sputum clearance when indicated. Growth, hearing, vision, and developmental monitoring are important during prolonged courses, and vaccination history and preventive measures should be reviewed.

Surveillance, vaccination, stewardship, and drug development are cross-cutting priorities. Robust surveillance systems allow clinicians to anticipate local resistance trends and adjust empiric therapy accordingly. Vaccination strategies that reduce overall disease incidence decrease the burden on treatment programs. Antimicrobial stewardship programs help preserve treatment options by guiding appropriate initiation, optimization, and de-escalation of therapy. Ongoing drug development expands therapeutic choices but may initially be available only through specialist or expanded-access pathways. Equitable access to diagnostics, medicines, and specialist care remains essential to translate clinical advances into improved outcomes globally.

Conclusion Effective management of drug-resistant mycobacterial infections rests on accurate diagnostics, carefully selected antibiotic combinations, tailored regimens for pulmonary and pediatric patients, and sustained adherence supports. Surveillance and stewardship protect therapeutic options while ongoing drug development and improved access can broaden choices over time. Multidisciplinary collaboration and use of local epidemiologic data help clinicians balance efficacy, safety, and resistance prevention in clinical practice.