Despite the sporadic detection of fluoroquinolone-resistant Shigella in Asia in the early 2000s and the subsequent global spread of ciprofloxacin-resistant (cipR) Shigella sonnei from 2010, fluoroquinolones remain the recommended therapy for shigellosis^{1,2,3,4,5,6,7}. The potential for cipR S. sonnei to develop resistance to alternative second-line drugs may further limit future treatment options⁸. Here, we aim to understand the evolution of novel antimicrobial resistant (AMR) S. sonnei variants after introduction into Vietnam. We found that cipR S. sonnei displaced the resident ciprofloxacin-susceptible (cipS) lineage while rapidly acquiring additional resistance to multiple alternative antimicrobial classes. We identified several independent acquisitions of extensively drug-resistant/multidrug-resistant-inducing plasmids, probably facilitated by horizontal transfer from commensals in the human gut. By characterizing commensal Escherichia coli from Shigella-infected and healthy children, we identified an extensive array of AMR genes and plasmids, including an identical multidrug-resistant plasmid isolated from both S. sonnei and E. coli in the gut of a single child. We additionally found that antimicrobial usage may impact plasmid transfer between commensal E. coli and S. sonnei. These results suggest that, in a setting with high antimicrobial use and a high prevalence of AMR commensals, cipR S. sonnei may be propelled towards pan-resistance by adherence to outdated international treatment guidelines.

尽管 2000 年代初在亚洲零星发现了耐氟喹诺酮类志贺菌，且随后自 2010 年起耐环丙沙星 (cipR)宋内志贺菌在全球蔓延，但氟喹诺酮类药物仍然是志贺菌病的推荐治疗方法^{1,2,3,4,5,6 ,7} . cipR S. sonnei对替代二线药物产生耐药性的可能性可能会进一步限制未来的治疗选择⁸ 。在这里，我们的目标是了解新型抗微生物药物耐药性 (AMR)宋内链球菌变种传入越南后的演变。我们发现 cipR S. sonnei取代了固有的环丙沙星敏感 (cipS) 谱系，同时迅速获得了对多种替代抗菌药物的额外耐药性。我们发现了几个独立获得的广泛耐药/多重耐药诱导质粒，可能是通过人类肠道共生体的水平转移来促进的。通过表征来自志贺氏菌感染和健康儿童的共生大肠杆菌，我们鉴定了一系列广泛的 AMR 基因和质粒，包括从单个儿童肠道中的宋内氏链球菌和大肠杆菌中分离出的相同的多重耐药质粒。我们还发现抗菌药物的使用可能会影响共生大肠杆菌和索尼沙门氏菌之间的质粒转移。这些结果表明，在抗菌药物使用率较高且 AMR 共生菌流行率较高的环境中，cipR S. sonnei可能会因遵守过时的国际治疗指南而产生泛耐药性。