Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India.

Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India.
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印度北方伤寒沙门氏菌独立谱系中阿奇霉素耐药性的自发出现。

DOI:
10.1093/cid/ciaa1773
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发表时间:
2021-03-01
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
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通讯作者:
Taneja N
Taneja N
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其他
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作者:
Carey ME;Jain R;Yousuf M;Maes M;Dyson ZA;Thu TNH;Nguyen Thi Nguyen T;Ho Ngoc Dan T;Nhu Pham Nguyen Q;Mahindroo J;Thanh Pham D;Sandha KS;Baker S;Taneja N

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抗生素耐药性(AMR)的出现和传播对伤寒的有效治疗和控制构成了重大威胁。正在爆发的广泛耐药伤寒沙门氏菌(S。在巴基斯坦,阿奇霉素已经成为南亚唯一广泛有效的伤寒口服抗菌药物。不幸的是,阿奇霉素耐药的S.随后在孟加拉国、巴基斯坦和尼泊尔报告了伤寒病菌。在此,我们的目的是了解66 S中AMR的分子基础。在印度北方的昌迪加尔郊区进行的一项横断面研究中,使用全基因组测序和系统发育分析分离出伤寒杆菌。我们发现了7个S。最近在孟加拉国发现acrB基因中具有R717 Q突变的伤寒菌可对阿奇霉素产生耐药性。七株阿奇霉素耐药的S.伤寒菌株也表现出gyrA(S83 F和D87 N)和parC(S80 I)基因的三重突变,并对环丙沙星耐药。这些当代的环丙沙星/阿奇霉素耐药分离株在遗传学上彼此不同,与孟加拉国、巴基斯坦和尼泊尔报道的分离株不同。印度北方出现的阿奇霉素耐药性伤寒反映了整个南亚正在出现的更广泛的问题,并说明该地区迫切需要引进伤寒结合疫苗。我们在印度北方的昌迪加尔发现了耐环丙沙星/阿奇霉素的伤寒沙门氏菌。在孟加拉国、巴基斯坦、尼泊尔和印度独立出现的耐环丙沙星/阿奇霉素伤寒,以及在巴基斯坦广泛耐药伤寒的持续传播,突出了南亚伤寒经许可的口服治疗的局限性。
The emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug-resistant Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin-resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal. Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis. We identified 7 S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the seven azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal. The independent emergence of azithromycin-resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines in the region. We identified ciprofloxacin/azithromycin-resistant Salmonella Typhi in Chandigarh in Northern India. The independent emergence of ciprofloxacin/azithromycin-resistant typhoid in Bangladesh, Pakistan, Nepal, and India and the continued spread of extensively drug-resistant typhoid in Pakistan highlight the limitations of licensed oral treatments for typhoid fever in South Asia.
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