Rapid emergence of extensively drug-resistant Shigella sonnei in France

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. There have been increasing reports of extensively drug-resistant (XDR) Shigella sonnei infections in recent years. In this laboratory surveillance study from France, the authors document the rise of XDR isolates from 2005 to 2021 and perform whole genome sequencing to investigate their genomic diversity and evolutionary history.