Rapid emergence of extensively drug-resistant Shigella sonnei in France

Abstract Shigella sonnei , the main cause of bacillary dysentery in high-income countries, has become increasingly resistant to antibiotics. We monitored the antimicrobial susceptibility of 7121 S. sonnei isolates collected in France between 2005 and 2021. We detected a dramatic increase in the proportion of isolates simultaneously resistant to ciprofloxacin (CIP), third-generation cephalosporins (3GCs) and azithromycin (AZM) from 2015. Our genomic analysis of 164 such extensively drug-resistant (XDR) isolates identified 13 different clusters within CIP-resistant sublineage 3.6.1, which was selected in South Asia ∼15 years ago. AZM resistance was subsequently acquired, principally through IncFII (pKSR100-like) plasmids. The last step in the development of the XDR phenotype involved various extended-spectrum beta-lactamase genes ( bla CTX-M-3 , bla CTX-M-15 , bla CTX-M-27 , bla CTX-M-55 , and bla CTX-M-134 ) carried by different plasmids (IncFII, IncI1, IncB/O/K/Z) or even integrated into the chromosome, and encoding resistance to 3GCs. This rapid emergence of XDR S. sonnei , including an international epidemic strain, is alarming, and good laboratory-based surveillance of shigellosis will be crucial for informed decision-making and appropriate public health action.