Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
Wellcome Trust Sanger Institute and the Department of Medicine, Cambridge University, Cambridge, United Kingdom.
PLoS Negl Trop Dis. 2018 Oct 11;12(10):e0006779. doi: 10.1371/journal.pntd.0006779. eCollection 2018 Oct.
The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies.
To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.
From these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.
伤寒的抗菌药物耐药性（AMR）趋势的时空变化尚未得到系统研究，此类信息对于确定干预措施以及规划可持续预防策略至关重要。
为了确定 AMR 的表型趋势，我们分析了 1973 年至 2018 年期间在 62 篇文献中报告的 13833 例个体伤寒沙门氏菌分离株，以确定随时间推移的 AMR 优势。我们还对 61 篇文献中报告的超过 4000 株分离株中存在的分子耐药决定因素进行了单独分析。亚洲的多重耐药（MDR）伤寒在氟喹诺酮耐药率高的情况下呈下降趋势，而非洲则呈上升趋势。gyrA（S83F、D87N）和 parC（S80I）中的 QRDR 突变是导致氟喹诺酮耐药的最常见机制。耐头孢菌素的伤寒沙门氏菌，被称为广泛耐药（XDR），是一个真正的威胁，并强调迫切需要部署 Vi 结合疫苗。
从这些观察结果来看，伤寒沙门氏菌中的 AMR 似乎将继续出现，导致治疗失败、抗菌药物政策改变以及在流行地区的伤寒沙门氏菌分离株和其他革兰氏阴性细菌中进一步出现耐药性。在流行地区部署伤寒结合疫苗来控制疾病可能是最好的防御措施。
