Poster : P-123 ; Linezolid resistance in clinical isolates of M. tuberculosis

Backgrounds: Linezolid is frequently used to treat MDR and XDR-TB. Development and mechanism of resistance in M. tuberculosis (Mtb), however, has not been investigated thoroughly. Methods: Mtb were isolated from patients who were failing on regimens containing linezolid and examined for the development of resistance by determining minimal inhibitory concentration (MIC) in 7H9 media. Nucleotide sequences of the genes known to be involved in linezolid resistance in other bacteria were determined. Results: Six among 14 isolates showed higher MIC of linezolid (4.0 - 16.0 μg/ml) than those of other isolates (0.25 - 0.5 μg/ml) implying the development of resistance. DNA sequencing of the 6 isolates reveled mutations either in rrl gene, encoding23S rRNA that forms binding site of linezolid, or rplC gene, encoding the ribosomal protein L3. Those mutations were not found in the linezolid-sensitive isolates. One isolates that accumulated mutations in both rrl and rplC showed the highestMIC, suggesting a possible synergistic effect of the mutations in conferring resistance. Two mutations in rrl are novel ones to be reported for the first time. Conclusion: Development of linezolid resistance was confirmed by the increase in MIC of clinical isolates. DNA sequencing of the resistant strains identified possible resistance mutations in two genes, rrl and rplC, including two novel mutations, enabling the understanding of detailed mechanism of linezolid resistance in Mtb. Collection of more information on the resistance mutations would allow rapid diagnosis of linezolid resistance.