Background: 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 (XDR) 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. Methods: Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole genome sequencing (WGS) and phylogenetic analysis. Results: We identified seven 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 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. Conclusions: 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 (TCVs) in the region.

中文翻译：

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印度北部鼠伤寒沙门氏菌独立谱系中对阿奇霉素耐药性的自发出现

背景：抗菌素耐药性（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。巴基斯坦持续爆发的广泛耐药（XDR）鼠伤寒沙门氏菌（S. Typhi）使得阿奇霉素成为​​南亚唯一剩下的对伤寒唯一广泛有效的口服抗菌剂。不祥的是，随后在孟加拉国，巴基斯坦和尼泊尔报道了对阿奇霉素具有抗性的伤寒沙门氏菌。方法：在这里，我们旨在通过全基因组测序（WGS）和系统发育分析，在印度北部昌迪加尔郊区进行的一项横断面研究中，了解分离出的66株伤寒杆菌AMR的分子基础。结果：我们确定了七个S。最近发现在acrB基因中具有R717Q突变的伤寒菌对孟加拉国的阿奇霉素具有抗性。耐阿奇霉素的鼠伤寒沙门氏菌中有六种在gyrA（S83F和D87N）和parC（S80I）基因中也表现出三重突变，并且对环丙沙星耐药。这些当代抗环丙沙星/阿奇霉素的分离株在系统发育上彼此不同，也与孟加拉国，巴基斯坦和尼泊尔报道的分离。结论：印度北部对阿奇霉素抗性伤寒的独立出现反映了整个南亚一个新出现的更广泛的问题，并说明了该地区迫切需要引入伤寒共轭疫苗（TCV）。鼠伤寒分离株在gyrA（S83F和D87N）和parC（S80I）基因中也表现出三重突变，并且对环丙沙星具有抗性。这些当代抗环丙沙星/阿奇霉素的分离株在系统发育上彼此不同，也与孟加拉国，巴基斯坦和尼泊尔报道的分离。结论：印度北部对阿奇霉素耐药性伤寒的独立出现反映了南亚一个新出现的更广泛的问题，并说明了该地区迫切需要引入伤寒缀合物疫苗（TCV）。鼠伤寒分离株在gyrA（S83F和D87N）和parC（S80I）基因中也表现出三重突变，并且对环丙沙星具有抗性。这些当代抗环丙沙星/阿奇霉素的分离株在系统发育上彼此不同，也与孟加拉国，巴基斯坦和尼泊尔报道的分离。结论：印度北部对阿奇霉素耐药性伤寒的独立出现反映了南亚一个新出现的更广泛的问题，并说明了该地区迫切需要引入伤寒缀合物疫苗（TCV）。