Azithromycin resistance in Shigella spp. in Southeast Asia

Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment, however antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolated in Vietnam and Laos were screened for susceptibility against azithromycin (15μg) by disc diffusion and minimum inhibitory concentration (MIC). Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin resistant S. sonnei using whole genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri (3.3%, MIC≥16g/L) and 16/294 S. sonnei (5.4%, MIC≥32g/L) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (19 mphA and 3 ermB). Susceptibility data demonstrated the acceptability of S. flexneri (MIC≥16g/L, zone≤15mm) and S. sonnei (MIC≥32g/L, zone≤11mm) breakpoints with <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei on at least seven occasions between 2000 and 2009, but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative management options for Shigella infections in endemic countries.