In Vitro activity comparison of linezolid, tedizolid, sutezolid and delpazolid against rapid growing Mycobacteria isolated in Beijing, China

Int J Infect Dis. 2021 Jun 30:S1201-9712(21)00544-0. doi: 10.1016/j.ijid.2021.06.055. Online ahead of print.

ABSTRACT

INTRODUCTION: The natural resistance of rapid growth Mycobacterium (RGM) to multiple antibiotics renders the treatment of caused infections less successful. Our objective was to evaluate the in vitro susceptibilities of four oxazolidinones against different RGM species.

METHODS: For four oxazolidinones, delpazolid, sutezolid, tedizolid and linezolid, the microplate AlamarBlue assay was performed to identify the minimal inhibitory concentration (MIC) of 32 reference strains and 115 clinical strains of different RGM species. The MIC breakpoint concentration was defined as 16 μg/mL for linezolid. Then the gene fragments associated with oxazolidinones resistance were amplified and sequenced, and mutation was defined in contrast with the sequences of the reference strains.

RESULTS: Tedizolid showed the strongest inhibitory activity against the M. abscessus isolates. Delpazolid exhibited better antimicrobial activity against the M. fortuitum isolates with 4-fold lower MIC values, in contrast with linezolid. The protein alignment and structure based analysis showed there might be no correlation between oxazolidinones resistance and mutations in rplC,rplD and 23srRNA genes in the tested RGM.

CONCLUSIONS: Tedizolid harbors the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best inhibitory activity against M. fortuitum, which provided important insights on the potential clinical application of oxazolidinones to treat RGM infections.

PMID:34216736 | DOI:10.1016/j.ijid.2021.06.055