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Nearly half of all\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants\u2014resistant to ciprofloxacin, ceftriaxone, and azithromycin\u2014has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      isolates collected during 2021\u20132023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      isolates carried the\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>CTX-M-15<\/jats:sub>\n                      gene from 2013 to 2019, its prevalence increased to 26% by 2022\u20132023. Among 38 ceftriaxone-resistant\n                      <jats:italic toggle=\"yes\">S. sonnei<\/jats:italic>\n                      isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>CTX-M-15<\/jats:sub>\n                      and\n                      <jats:italic toggle=\"yes\">mphA<\/jats:italic>\n                      ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid\u2019s transferability. We report a rising trend in third-generation cephalosporin resistance among\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      spp., primarily driven by the spread of extended-spectrum \u03b2-lactamase-producing\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      and the emergence of XDR\n                      <jats:italic toggle=\"yes\">S. sonnei<\/jats:italic>\n                      . These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      to mitigate this growing public health threat.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                        is a leading cause of diarrheal disease globally and has been prioritized by the World Health Organization due to its rapid acquisition of antimicrobial resistance. Our prospective surveillance in Kolkata, India, reveals a worrisome escalation of third-generation cephalosporin resistance over the past decade, primarily associated with the spread of\n                        <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                        <jats:sub>CTX-M-15<\/jats:sub>\n                        and the emergence of extensively drug-resistant (XDR)\n                        <jats:italic toggle=\"yes\">S. sonnei<\/jats:italic>\n                        . The detection of plasmids carrying both\n                        <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                        <jats:sub>CTX-M-15<\/jats:sub>\n                        and\n                        <jats:italic toggle=\"yes\">mphA<\/jats:italic>\n                        , coupled with evidence of their transferability, highlights the potential for accelerated dissemination of multidrug resistance. When compared with a global data set of international genomes, the Kolkata XDR isolates were found to cluster closely with isolates reported from England. By linking local surveillance with global genomic context, our findings provide critical insights for treatment guidelines, antimicrobial stewardship, and the design of international containment strategies aimed at curbing the rise of cephalosporin- and azithromycin-resistant\n                        <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02824-25","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:01:26Z","timestamp":1784898086000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Escalation of CTX-M-producing extensively drug-resistant\n                    <i>Shigella<\/i>\n                    spp. in Kolkata, India, following the COVID-19 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