Linezolid resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Iran

Abstract

The management of multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) presents a main challenge and the drug options for treating these infections are very limited. Linezolid (LNZ) has recently been approved for the treatment of MDR and XDR-TB. But, there are narrow data on genotypic and phenotypic LNZ resistance in clinical isolates. So, we aimed to determine the prevalence of LNZ resistance and to identify the mutations associated with LNZ resistance among clinical MDR-TB isolates. The minimum inhibitory concentration (MIC) values of LNZ for 22 MDR-TB isolates were determined by broth microdilution method. All MDR-TB isolates were sequenced in the rrl and rplC genes conferring LNZ resistance. LNZ resistance was found in 3 (13.6%) of 22 MDR-TB isolates. The MICs of LNZ were 8 μg/mL for two isolates and 16 μg/mL for one isolate. The 421 (A/G) and 449 (T/A) mutations in rplC gene were detected in one of the LNZ-resistant isolates. There was no mutation in rrl gene. The results reveal that the prevalence of LNZ-resistant isolates is 13.6% among MDR-TB isolates and drug susceptibility testing (DST) against LNZ is useful in the management of complicated and drug-resistant cases. However, further studies could identify other possible genetic mechanism of resistance in TB.

Expert consensus statement on therapeutic drug monitoring and individualization of linezolid

“…tuberculosis , it should estimate the AUC/MIC based on the local drug resistance profile of M . tuberculosis ( 87 – 91 ).…”

Mutations and insights into the molecular mechanisms of resistance of Mycobacterium tuberculosis to first-line

“…The mutation C154R in RplC is one of the most prevalent ones (Ushtanit et al, 2021). Nevertheless, other mutations reported to LZD were summarized by Kadura et al (2020) and Khosravi et al (2021). The other prevalent mutations include G2270T, G2299, G2746A, G2814T and C2848A for Rrl.…”

“…These authors also identified 2 polymorphisms in LZD resistance strains for rplC, V141I and I150N. However, they have not been completely validated to be the unique reason for LZD resistance (Kadura et al, 2020;Khosravi et al, 2021).…”