Azithromycin is increasingly being used for the treatment of
shigellosis despite a lack of interpretative guidelines and with limited clinical evidence. The present study determined
azithromycin susceptibility and correlated this with
macrolide-resistance genes in Shigella spp. isolated from stool specimens in Vellore, India. The susceptibility of 332 Shigella isolates to
azithromycin was determined using the disc diffusion method. Of these, 31 isolates were found to be
azithromycin resistant. The
azithromycin minimum inhibitory concentration (MIC) was determined using the broth microdilution method. In addition, isolates were screened for mphA and ermB genes using conventional PCR. Furthermore, an isolate that was positive for resistance genes was subjected to complete genome analysis, and was analysed for mobile genetic elements. The
azithromycin MIC for the 31 resistant Shigella isolates ranged between 2 and 16 mg l-1. PCR results showed that a single isolate of Shigella sonnei carried a mphA gene. Complete genome analysis revealed integration of an IncFII plasmid into the chromosome of S. sonnei , which was also found to carry the following resistance genes: sul1, bla DHA1, qnrB4, mphA, tetR. Mutations in the
quinolone-resistance-determining region (QRDR) were also observed. Additionally, prophages, insertion sequences and integrons were identified. The novel finding of IncFII plasmid integration into the chromosome of S. sonnei highlights the potential risk of Shigella spp. becoming resistance to
azithromycin in the future. These suggests that it is imperative to monitor Shigella susceptibility and to study the resistance mechanism of Shigella to
azithromycin considering the limited treatment choices for
shigellosis.