Abstract

Background and objectives: 

The high intrinsic antibiotic resistance of Mycobacterium abscessus complex (MABC) makes it crucial to discover effective drugs for the treatment of MABC. Therefore, this study aimed to investigate and compare in vitro and intracellular activities of several drugs of interest against MABC, particularly the difference between rough and smooth morphotypes. 

Materials and methods:

Using broth microdilution, drug susceptibility testing was performed for three drugs of interest (Bedaquiline, Delamanid, Tedizolid) as well as Clarithromycin and Amikacin on clinical MABC isolates. Among these MABC isolates, two strains with similar bacterial characteristics but different morphotypes would be chosen for THP-1 cell infection experiments. 

Results:

Of the tested drugs, only Bedaquiline had a lower minimal inhibitory concentration than Clarithromycin and Amikacin regardless of colony morphotypes on 57 MABC isolates. THP-1 cell infection experiments were performed with two strains, V388 (with rough morphotype) and V1170 (with smooth morphotype). It was found that both Bedaquiline and Clarithromycin could significantly inhibit the growth of V388 in macrophages while Bedaquiline rather than Clarithromycin could inhibit the intracellular growth of V1170. Both Bedaquiline and Clarithromycin could inhibit intracellular growth of V388 more effectively than V1170. The viability of THP-1 cell was significantly reduced when infected with V388 after treatment with either Bedaquiline or Clarithromycin but stable for V1170 strain.

Conclusions:

The results of this study suggested that Bedaquiline is effective in the treatment of MABC infection regardless of colony morphotypes.