Mycobacterium abscessus strain variability in preclinical drug development: does it really matter?

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Novel treatment options for Mycobacterium abscessus infections are critical.
• Standard in vitro assays often use the ATCC 19977 strain, but its representativeness for diverse clinical isolates is uncertain.
• Establishing reliable preclinical drug activity assays is essential for Mycobacterium abscessus complex (MAC) drug development.

Purpose of the Study:

• To determine if the relationship between Minimum Inhibitory Concentration (MIC) and quantitative antimycobacterial activity differs between the M. abscessus ATCC 19977 strain and clinical isolates.
• To validate the use of the ATCC 19977 strain in preclinical drug activity assays for MAC.

Main Methods:

• Experiments utilized M. abscessus ATCC 19977 and six clinical isolates representing different subspecies and morphotypes.
• Cultures were exposed to amikacin, imipenem, and clofazimine at MIC-standardized concentrations.
• Mycobacterial load was assessed over time to evaluate drug activity.

Main Results:

• The concentration- and time-dependent activity of amikacin, imipenem, and clofazimine was similar across the tested clinical isolates.
• Minimal variations in drug activity were observed when comparing the ATCC 19977 strain to clinical isolates.

Conclusions:

• In vitro drug activity against the M. abscessus ATCC 19977 strain appears indicative of drug behavior against clinical isolates within the M. abscessus complex.
• Including a smooth morphotype clinical isolate alongside ATCC 19977 is recommended for robust interpretation of in vitro drug activity assays in MAC preclinical drug development.