Abstract:

Objective To evaluate the susceptibility of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains against SQ109, an analogue of ethambutol (EMB, a new anti-TB drug), and to provide evidence for the clinical application of SQ109.Methods Two hundred and twenty three strains including 109 MDR-TB and 114 XDR-TB were collected from the patients seeking health care in Beijing chest hospital from July 2014 to December 2016. The minimum inhibitory concentrations (MIC) of MTB isolates against SQ109 were detected by broth dilution micro-plate alamar blue assay. The epidemiological cutoff (ECOFF) value was determined on the basis of distribution of MIC values. RD207 gene was used to distinguish Beijing genotype and non-Beijing genotype. Difference in SQ109 resistance rates between groups was compared. According to the results of clinical drug sensitivity test, the EMB resistant strains were isolated, and SQ109 resistance rate was compared between EMB resistant and sensitive strains.Results The ECOFF value was determined to be 1.000 mg/L according to the frequency distribution of MIC against SQ109. The resistance rate was 4.4% (5/114) and 0.0% among XDR-TB and MDR-TB isolates, respectively. There was no statistical difference in SQ109-resisitant rate between MDR-TB and XDR-TB (Fisher exact probabilities, P>0.05). Eight isolates out of 109 MDR strains and 10 isolates out of 114 XDR strains were classified as non-Beijing genotype. The resistant rate of the Beijing geno-type strain was 2.4% (5/205), while no non-Beijing genotype strain harbored SQ109 resistance. Statistical analysis revealed that no significant difference was observed in SQ109 resistance rate between Beijing and non-Beijing group (Fisher exact probabilities, P>0.05). Of the 223 strains, there were 138 EMB sensitive strains and 85 EMB resistant strains. Among EMB sensitive strains, only one was resistant strain against SQ109, and the resistance rate was 0.7% (1/138). Among the EMB resistant strains, 4 strains were resistant to SQ109, and the resistance rate was 4.7% (4/85). The difference in SQ109 resistance rate between EMB sensitive and resistant strains was not statistically significant (Fisher exact probabilities, P>0.05).Conclusion SQ109 exhibits favorable efficacy against MDR- and XDR-TB isolates in vitro. In addition, there is no statistical correlation between SQ109 resistance and Beijing genotype or between EMB resistance and SQ109 resistance.

Key words: Mycobacterium tuberculosis, Drug resistance, multiple, bacterial, Genotype, Causality, SQ109