Azithromycin Resistance in Shigella spp. in Southeast Asia
Darton TC., Tuyen HT., The HC., Newton PN., Dance DAB., Phetsouvanh R., Davong V., Campbell JI., Hoang NVM., Thwaites GE., Parry CM., Thanh DP., Baker S.
<jats:title>ABSTRACT</jats:title> <jats:p> Infection by <jats:named-content content-type="genus-species">Shigella</jats:named-content> spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment; however, antimicrobial resistance in <jats:named-content content-type="genus-species">Shigella</jats:named-content> spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian <jats:named-content content-type="genus-species">Shigella</jats:named-content> isolates and use these data to assess appropriate susceptibility breakpoints. <jats:named-content content-type="genus-species">Shigella</jats:named-content> isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 μg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant <jats:named-content content-type="genus-species">Shigella sonnei</jats:named-content> isolates using whole-genome sequences. From 475 available <jats:named-content content-type="genus-species">Shigella</jats:named-content> spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 <jats:named-content content-type="genus-species">S. flexneri</jats:named-content> isolates (3.3%, MIC ≥ 16 g/liter) and 16/294 <jats:named-content content-type="genus-species">S. sonnei</jats:named-content> isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates ( <jats:italic>mphA</jats:italic> in 19 isolates and <jats:italic>ermB</jats:italic> in 3 isolates). The susceptibility data demonstrated the acceptability of the <jats:named-content content-type="genus-species">S. flexneri</jats:named-content> (MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and <jats:named-content content-type="genus-species">S. sonnei</jats:named-content> (MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese <jats:named-content content-type="genus-species">S. sonnei</jats:named-content> isolates 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 the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of <jats:named-content content-type="genus-species">Shigella</jats:named-content> infections in countries where <jats:named-content content-type="genus-species">Shigella</jats:named-content> is endemic. </jats:p>