BACKGROUND Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION PROSPERO CRD42018029432.

中文翻译：

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1990 年至 2018 年全球耐药性肠热病：系统评价和荟萃分析。


背景技术抗菌素耐药性（AMR）对全球健康构成日益严重的威胁。每年有 > 1400 万肠热病病例和 > 135,000 人死亡。该疾病主要通过抗菌治疗来控制，但由于抗菌素耐药性，控制变得越来越困难。我们的目标是评估全球肠沙门氏菌血清型伤寒和甲型副伤寒感染中 AMR 的患病率和地理分布，评估问题的严重程度，并促进创建 AMR 患病率的地理空间地图，以帮助有针对性的公共卫生干预。方法 我们通过搜索 7 个数据库来查找 1990 年至 2018 年间发表的研究，对文献进行了系统回顾。我们对分离株进行了重新分类，以便分析研究期间的氟喹诺酮耐药趋势。通过森林图说明了个别研究中多药耐药性 (MDR) 和氟喹诺酮类不敏感 (FQNS) 的患病率，并进行了随机效应荟萃分析，按全球疾病负担 (GBD) 区域和 5 年时间进行分层时期。使用 I2 统计数据评估异质性。我们对头孢曲松和阿奇霉素耐药性进行了描述性分析。结果 我们鉴定了 4557 篇文章，其中 384 篇，包括 124,347 个分离株（94,616 个伤寒沙门氏菌和 29,731 个甲型副伤寒沙门氏菌）符合预先指定的纳入标准。大多数（276/384；72%）研究来自南亚；确定了 40 篇 (10%) 文章来自撒哈拉以南非洲地区。除了南亚的耐多药伤寒沙门氏菌在 1990 年至 2018 年间有所下降，以及耐多药甲型副伤寒沙门氏菌仍保持在较低水平外，所有地区对所有抗菌药物的耐药性趋势都在恶化。我们发现非洲和中东存在一些数据差距。 发现抗菌药物敏感性测试 (AST) 报告不完整且缺乏质量保证。解释 耐药性肠热病在低收入和中等收入国家普遍存在，而且情况正在恶化。必须采取公共卫生和临床措施，包括改善水质和卫生设施、部署伤寒沙门氏菌疫苗接种以及明智地选择治疗方法。然而，甲型副伤寒沙门氏菌尚无获得许可的疫苗。迫切需要标准化 AST 数据报告和外部质量控制评估的推出，以促进循证政策和实践。试用注册 PROSPERO CRD42018029432。