Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins

作者：Elizabeth J. Klemm, Sadia Shakoor, Andrew J. Page, Farah Naz Qamar, Kim Judge, Dania Khalid Saeed, Vanessa Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Rehan Saleem, Zahra Hasan, Gordon Dougan, Rumina Hasan · 发表于：mBio · 年份：2018 · DOI：10.1128/mbio.00105-18 · 被引用次数：666 · 研究领域：Antibiotic Resistance in Bacteria、Salmonella and Campylobacter epidemiology、Bacteriophages and microbial interactions

ABSTRACT Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S . Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S . Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the bla CTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited hig...