Objective: Treatment choices for Mycobacterium abscessus  (M. abscessus ) infections are very limited, and the prognosis is generally poor. Effective new antibiotics or repurposing existing antibiotics against M. abscessus  infection are urgently needed. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a member of the lipophilic weak acid class, is known as an efflux pump inhibitor for Mycobacterium tuberculosis . The aim of this study was to determine the inhibitory activity of CCCP as a potential novel antibiotic against M. abscessus .
Methods: A total of 47 reference strains of different mycobacterial species and 60 clinical isolates of M. abscessus  were enrolled. In vitro inhibitory activity of CCCP was accessed using microplates alamar blue method with the reference and clinical isolates. The activity of CCCP against intracellular M. abscessus  residing within macrophage was also evaluated by intracellular colony numerating assay.
Results: CCCP exhibited good activity against M. abscessus  clinical isolates in vitro, the minimum inhibitory concentration (MIC) ranged from 0.47 μg/mL to 3.75 μg/mL, with a MIC₅₀ of 1.875 μg/mL and MIC₉₀ of 3.75 μg/mL. At concentrations safe for the cells, CCCP exhibited highly intracellular bactericidal activities against M. abscessus  and M. massiliense  reference strains, with inhibitory rates of 84.8%± 8.8% and 72.5%± 13.7%, respectively. CCCP demonstrated bactericidal activity against intracellular M. abscessus  that was comparable to clarithromycin, and concentration-dependent antimicrobial activity against M. abscessus  in macrophages was observed. In addition, CCCP also exhibited good activities against most reference strains of rapidly growing mycobacterial species.
Conclusion: CCCP could be a potential candidate of novel antimicrobiological agent to treat M. abscessus  infection.
Keywords: Mycobacterium abscessus , carbonyl cyanide 3-chlorophenylhydrazone, minimum inhibitory concentration, intracellular bactericidal activity