Toward better cures for Mycobacterium abscessus lung disease

Area of Science:

• Infectious Diseases
• Antimicrobial Resistance
• Pulmonary Medicine

Background:

• Mycobacterium abscessus (Mab) causes severe lung infections with limited treatment options.
• Mab infections share similarities with tuberculosis but have poorer outcomes and fewer approved therapies.
• Current treatments for Mab disease are often ineffective, toxic, and administered parenterally.

Purpose of the Study:

• To identify factors contributing to poor Mab disease cure rates.
• To propose preclinical strategies for developing safe, sterilizing, and injectable-free Mab treatment regimens.
• To highlight knowledge and tool gaps in Mab drug discovery and clinical development.

Main Methods:

• Discussion of intrinsic resistance and pathogen persistence in Mab.
• Proposal of prioritizing oral bactericidal antibiotics and early drug combination testing.
• Emphasis on optimizing novel drug leads and considering lung-specific pharmacokinetic-pharmacodynamic targets.

Main Results:

• Identified intrinsic resistance and persistence as key challenges in Mab treatment.
• Proposed a multi-pronged preclinical strategy including oral agents and combination therapies.
• Highlighted the need for improved preclinical models and translational tools for Mab drug discovery.

Conclusions:

• Urgent need for novel, safe, and effective treatment regimens for Mycobacterium abscessus lung infections.
• Development requires prioritizing oral bactericidal agents, combination strategies, and optimized drug discovery pipelines.
• Collaborative efforts between academia, industry, and government are crucial for advancing Mab therapeutics.