Abstract

Dear Editor:
We read with great interest the article by Hu et al. 1 The authors highlight that fluoroquinolone (FQ) resistance among multidrug-resistant (MDR) Mycobacterium tuberculosis remains the most serious threat to tuberculosis (TB) control. Although the authors confirm previous findings from Yang et al. in China where M. tuberculosis Beijing strain transmission does not necessarily occur in clusters, Hu et al. only focused on describing MDR Beijing strains identified using 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) genotyping. 2 Interestingly, they found a group of ancestral Beijing strains had more resistance mutations in the gyrB gene than modern Beijing strains. This finding is linked to evolutionary events in modern Beijing linages. Nevertheless, we would like to highlight a few points.
First, it would be helpful to discuss whether the 229 cases correspond to previously treated TB cases or new cases. This is fundamental for understanding FQ resistance gene diversity among primary or secondary resistance cases. 3 In contrast, the exact cluster localization would help to outline the appearance of recent new cases at the provincial level. Such an approach would clarify distinguish the presence of community or regional transmission.
It is also worth noting that using four hypervariable loci to genotype this collection would better discriminate clustering among these Beijing strains. In a previous study, the addition of these four loci to the 24 MIRU-VNTR panel identified a subcluster of Beijing strains. 4 The use of Beijing hypervariable loci would also allow the authors to draw possible conclusions supporting the dispersion of a Beijing strain clone within this population. In a recent study by Mokrousov et al., the authors applied 28-loci MIRU-VNTRs and were able to subtype the clones 14717-15 and 1071-32 with the highest risk of MDR or pre-XDR/XDR transmission among the cases. 5
Similarly, another study using 28-loci MIRU-VNTRs was able to describe two subtypes, including the Beijing subtype that is transmitted more frequently and involved in the largest number of cases. 6 Thus, by using 28-loci MIRU-VNTR, Beijing strains can be typified with higher resolution, stability, and epidemiological relevance. We believe that future studies applying these additional loci will help to better discriminate a clone or subcluster among MDR Beijing strains.
We acknowledge that another study based on whole genome sequencing on the new isolates was conducted by Zhao et al. in the same city and population 2 years after Hu et al. report (January 2018–December 2020). 7 This new study revealed the emergence of MDR and rifampicin-resistant TB strains led by the transmission of lineage 2 Beijing strains with respect to other lineages. This study also identified strains with a higher resistance to FQ [63% (28/44)]. Together, both studies provide strong evidence for Beijing strains acquiring FQ resistance within Chongqing, China.
In summary, we applaud the authors' efforts to outline the Beijing strains' transmission patterns. This characterization indicates that the strains are transmitted at the population level and not in clusters, and the transmission of new cases is due to the circulation of prevalent strains. Moreover, the finding that not all MDRs have the same resistance in FQ genes, which varies according to the study population, is significant.
