Distributions of Minimum Inhibitory Concentration for Delpazolid and Linezolid in Drug-resistant Mycobacterium Tuberculosis in South Korea

Background As a recommendation for the treatment of multidrug-resistant (MDR) / rifampicin-resistant tuberculosis (RR) in WHO guidelines, the use of linezolid is strongly recommended for longer MDR-TB regimens. However, there are many reports of side effects from using linezolid. Delpazolid is a new antibiotic of an Oxazolidinone family, same as linezolid. Delpazolid was reported to be safer compared to linezolid with lower adverse effects. In this study, minimum Inhibitory Concentration (MIC) of drug-resistant TB isolates was measured for linezolid and delpazolid, and the distribution was confirmed. Methods A total of 514 resistant-TB clinical isolates were randomly selected from the Korea Mycobacterium Resource Center at the Korean institute of tuberculosis; respectively, 1 isoniazid-resistant, 389 MDR, 100 RR, and 24 extensively-resistant TB. The MIC test of linezolid and delpazolid was performed using Middlebrook 7H9 broth with 10% oleic-albumin-dextrose-catalase and 2,3 diphenyl-5-(2-thienyl)-tetrazolium chloride by broth microdilution Method in 96-well microplate. Results The MIC90 of linezolid and delpazolid were 0.5 mg/L and 1 mg/L, respectively. Additionally, for the MIC distribution, tentative epidemiological cutoff (ECOFF) of linezolid and delpazolid were determined as 1 mg/L and 4 mg/L. According to the ECOFFs, the number of resistant strains was 16 (3.11 %) and 10 (1.95 %) isolates for linezolid and delpazolid. Furthermore, 9 isolates were confirmed to be resistant to both antibiotics. Conclusions In this study, we compared the MIC distributions of linezolid and delpazolid in drug resistant-TB isolates, and confirmed the MIC90 and ECOFF values, and we also identified resistant isolates of linezolid and delpazolid, respectively. In further studies, the detailed resistance mechanism will be investigated in 8 isolates which have different resistance to the same oxazolidinone antibiotics. Finally, it will be confirmed whether there is a new mechanism of resistance that is still unknown for 9 strains having common resistance.