印度儿童抗菌药物耐药性的地理和基因组决定因素：一项系统综述和荟萃分析。
完整摘要 · 中文译文
背景：抗菌药物耐药性（AMR）是一个重大的公共卫生挑战，尤其是在低收入和中等收入国家的儿童群体中，特别是在印度，其儿童感染负担较高。然而，目前仍缺乏具有地理分层、具有全国代表性的儿童特异性AMR估计数据。我们开展了一项系统综述和荟萃分析，以明确印度儿童中AMR的严重程度及区域差异。 方法：我们按照PRISMA 2020和乔安娜·布里格斯研究所指南开展了一项系统综述和荟萃分析。检索了PubMed/MEDLINE、Scopus和Cochrane图书馆，检索时间从建库至2025年12月，纳入报告印度儿童（≤18岁）细菌分离株抗菌药物耐药性的研究。鉴于不同病原体、抗生素类别及诊疗环境之间存在显著的临床和方法学异质性，我们按地理区域对关键耐药表型进行了分层随机效应荟萃分析。 结果：共47项研究符合纳入标准，其中23项纳入定量综合。印度各地区AMR存在显著的地理异质性。纳入各项合并估计的研究数量为2至8项，异质性（I²）范围为19%至79%。新生儿重症监护病房分离株的碳青霉烯耐药率从中印度地区的12%（95% CI 8-18）到北印度地区的80%（70-88）不等。超广谱β-内酰胺酶产生率在大多数地区持续处于高水平（60-80%），但中印度地区较低（38%）。 耐甲氧西林金黄色葡萄球菌的流行率从35%（26-44）到61%（49-72）不等。北部、南部和东部/东北部地区的氟喹诺酮耐药率超过85%，而粘菌素耐药率在全国范围内仍≤8%。基因组数据显示blaCTX-M-15广泛传播，碳青霉烯酶基因（blaNDM、blaOXA）呈区域性聚集，支持克隆传播和水平基因转移两种机制。 结论：印度儿童抗菌药物耐药性高度普遍且存在地域异质性，碳青霉烯耐药率地区间差异最高可达五倍。在高负担地区，这些耐药水平可能损害标准经验性治疗的有效性，尤其是在新生儿和重症监护环境中。这些发现支持迫切需要制定区域性经验性治疗指南、以儿科为重点的抗菌药物管理方案，以及表型-基因组整合监测系统。
完整摘要 · 英文原文
BACKGROUND: Antimicrobial resistance (AMR) is a major public health challenge, especially in the pediatric population in low- and middle-income countries, particularly India, where the burden of pediatric infections is high. However, nationally representative, pediatric-specific estimates of AMR with geographic stratification remain lacking. We conducted a systematic review and meta-analysis to define the magnitude and regional variation of AMR among Indian children. METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 and the Joanna Briggs Institute guidelines. PubMed/MEDLINE, Scopus, and the Cochrane Library were searched from inception to December 2025 for studies reporting antimicrobial resistance in bacterial isolates from children (≤ 18 years) in India. Given substantial clinical and methodological heterogeneity across pathogens, antibiotic classes, and settings, we conducted stratified random-effects meta-analyses by geographic zone for key resistance phenotypes. RESULTS: Forty-seven studies met the inclusion criteria, of which 23 contributed to the quantitative synthesis. Pronounced geographic heterogeneity in AMR was observed across India. The number of studies contributing to each pooled estimate ranged from 2 to 8, and heterogeneity (I²) ranged from 19% to 79%. Carbapenem resistance among neonatal intensive care unit isolates ranged from 12% (95% CI 8-18) in Central India to 80% (70-88) in North India. Extended-spectrum β-lactamase production was consistently high (60-80%) across most regions, but lower in Central India (38%). Methicillin-resistant Staphylococcus aureus prevalence ranged from 35% (26-44) to 61% (49-72). Fluoroquinolone resistance exceeded 85% in North, South, and East/Northeast regions, whereas colistin resistance remained ≤ 8% nationally. Genomic data demonstrated widespread dissemination of blaCTX-M-15 and regional clustering of carbapenemase genes (blaNDM, blaOXA), supporting both clonal spread and horizontal gene transfer. CONCLUSION: Antimicrobial resistance in Indian children is highly prevalent and geographically heterogeneous, with up to five-fold regional differences in carbapenem resistance. In high-burden regions, these resistance levels are likely to compromise the effectiveness of standard empirical therapies, particularly in neonatal and critical care settings. These findings support the urgent need for region-specific empirical treatment guidelines, pediatric-focused antimicrobial stewardship, and integrated phenotypic-genomic surveillance systems.