Resistance mechanisms and tedizolid susceptibility in clinical isolates of linezolid-resistant bacteria in Japan.

OBJECTIVES

Studies combining linezolid resistance mechanisms and tedizolid susceptibility in linezolid-resistant clinical isolates are scarce. This study investigated the linezolid resistance mechanisms and tedizolid susceptibility of linezolid-resistant strains isolated clinically in Japan.

METHODS

We analysed 25 linezolid-resistant strains of and isolated from Japanese hospitals between 2015 and 2021. MICs of linezolid and tedizolid were determined using the agar plate dilution method. Each 23S rRNA copy was amplified by PCR, sequenced and analysed for mutations. The linezolid resistance genes , , , and were also detected by PCR.

RESULTS

Drug susceptibility tests revealed that five linezolid-resistant isolates had low (≤1 mg/L) tedizolid MICs. Resistance mechanisms included the G2576T mutation in 23S rRNA, the T2504A mutation and the resistance genes , and . The T2504A mutation was identified in one isolate, which exhibited linezolid and tedizolid MICs of 64 and 32 mg/L, respectively.

CONCLUSIONS

Some linezolid-resistant isolates demonstrated low (≤1 mg/L) tedizolid MICs. To determine whether tedizolid susceptibility testing should be performed on linezolid-resistant isolates, more linezolid-resistant isolates should be collected and tested for tedizolid MICs. Tedizolid MICs were 2-3 doubling dilutions lower than linezolid MICs. The results of this study suggest that future research should investigate whether the T2504A mutation contributes to tedizolid resistance. To our knowledge, this is the first study to report tedizolid susceptibility in with the T2504A mutation and in isolate harbouring this mutation.