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Abstract：
Klebsiella pneumoniae is the most common pathogen causing neonatal infections, leading to high mortality worldwide. Along with increasing antimicrobial use in neonates, carbapenem-resistant K. pneumoniae (CRKP) has emerged as a severe challenge for infection control and treatment. However, no comprehensive systematic review is available to describe the global epidemiology of neonatal CRKP infections. We therefore performed a systematic review of available data worldwide and combined a genome-based analysis to address the prevalence, clonal diversity, and carbapenem resistance genes of CRKP causing neonatal infections.
We performed a systematic review of studies reporting population-based neonatal infections caused by CRKP in combination with a genome-based analysis of all publicly available CRKP genomes with neonatal origins. We searched multiple databases (PubMed, Web of Science, Embase, Ovid MEDLINE, Cochrane, bioRxiv, and medRxiv) to identify studies that have reported data of neonatal CRKP infections up to June 30, 2022. We included studies addressing the prevalence of CRKP infections and colonization in neonates but excluded studies lacking the numbers of neonates, the geographical location, or independent data on Klebsiella or CRKP isolates. We used narrative synthesis for pooling data with JMP statistical software. We identified 8,558 articles and excluding those that did not meet inclusion criteria. We included 128 studies, none of which were preprints, comprising 127,583 neonates in 30 countries including 21 low- and middle-income countries (LMICs) for analysis. We found that bloodstream infection is the most common infection type in reported data. We estimated that the pooled global prevalence of CRKP infections in hospitalized neonates was 0.3% (95% confidence interval [CI], 0.2% to 0.3%). Based on 21 studies reporting patient outcomes, we found that the pooled mortality of neonatal CRKP infections was 22.9% (95% CI, 13.0% to 32.9%). A total of 535 neonatal CRKP genomes were identified from GenBank including Sequence Read Archive, of which 204 were not linked to any publications. We incorporated the 204 genomes with a literature review for understanding the species distribution, clonal diversity, and carbapenemase types. We identified 146 sequence types (STs) for neonatal CRKP strains and found that ST17, ST11, and ST15 were the 3 most common lineages. In particular, ST17 CRKP has been seen in neonates in 8 countries across 4 continents. The vast majority (75.3%) of the 1,592 neonatal CRKP strains available for analyzing carbapenemase have genes encoding metallo-β-lactamases and NDM (New Delhi metallo-β-lactamase) appeared to be the most common carbapenemase (64.3%). The main limitation of this study is the absence or scarcity of data from North America, South America, and Oceania.
CRKP contributes to a considerable number of neonatal infections and leads to significant neonatal mortality. Neonatal CRKP strains are highly diverse, while ST17 is globally prevalent and merits early detection for treatment and prevention. The dominance of blaNDM carbapenemase genes imposes challenges on therapeutic options in neonates and supports the continued inhibitor-related drug discovery.
We performed a systematic review of studies reporting population-based neonatal infections caused by CRKP in combination with a genome-based analysis of all publicly available CRKP genomes with neonatal origins. We searched multiple databases (PubMed, Web of Science, Embase, Ovid MEDLINE, Cochrane, bioRxiv, and medRxiv) to identify studies that have reported data of neonatal CRKP infections up to June 30, 2022. We included studies addressing the prevalence of CRKP infections and colonization in neonates but excluded studies lacking the numbers of neonates, the geographical location, or independent data on Klebsiella or CRKP isolates. We used narrative synthesis for pooling data with JMP statistical software. We identified 8,558 articles and excluding those that did not meet inclusion criteria. We included 128 studies, none of which were preprints, comprising 127,583 neonates in 30 countries including 21 low- and middle-income countries (LMICs) for analysis. We found that bloodstream infection is the most common infection type in reported data. We estimated that the pooled global prevalence of CRKP infections in hospitalized neonates was 0.3% (95% confidence interval [CI], 0.2% to 0.3%). Based on 21 studies reporting patient outcomes, we found that the pooled mortality of neonatal CRKP infections was 22.9% (95% CI, 13.0% to 32.9%). A total of 535 neonatal CRKP genomes were identified from GenBank including Sequence Read Archive, of which 204 were not linked to any publications. We incorporated the 204 genomes with a literature review for understanding the species distribution, clonal diversity, and carbapenemase types. We identified 146 sequence types (STs) for neonatal CRKP strains and found that ST17, ST11, and ST15 were the 3 most common lineages. In particular, ST17 CRKP has been seen in neonates in 8 countries across 4 continents. The vast majority (75.3%) of the 1,592 neonatal CRKP strains available for analyzing carbapenemase have genes encoding metallo-β-lactamases and NDM (New Delhi metallo-β-lactamase) appeared to be the most common carbapenemase (64.3%). The main limitation of this study is the absence or scarcity of data from North America, South America, and Oceania.
CRKP contributes to a considerable number of neonatal infections and leads to significant neonatal mortality. Neonatal CRKP strains are highly diverse, while ST17 is globally prevalent and merits early detection for treatment and prevention. The dominance of blaNDM carbapenemase genes imposes challenges on therapeutic options in neonates and supports the continued inhibitor-related drug discovery.
摘要：
背景：肺炎克雷伯菌是引起新生儿感染的最常见病原体，导致全球高死亡率。随着新生儿抗菌药物使用的增加，耐碳青霉烯类肺炎克雷伯菌（CRKP）已成为感染控制和治疗的严峻挑战。然而,目前尚无全面的系统评价来描述新生儿CRKP感染的全球流行病学.因此，我们对全球现有数据进行了系统回顾，并结合基于基因组的分析来解决患病率问题。克隆多样性，引起新生儿感染的CRKP的碳青霉烯类耐药基因。
结果：我们对报告由CRKP引起的以人群为基础的新生儿感染的研究进行了系统评价，并对所有公开的新生儿来源的CRKP基因组进行了基于基因组的分析。我们搜索了多个数据库(PubMed，WebofScience,Embase,OvidMEDLINE,科克伦,bioRxiv,和medRxiv），以确定报告截至2022年6月30日新生儿CRKP感染数据的研究。我们纳入了新生儿CRKP感染和定植患病率的研究，但排除了缺乏新生儿数量的研究。地理位置,或克雷伯菌或CRKP分离株的独立数据。我们使用JMP统计软件对数据进行叙述性综合。我们确定了8,558篇文章，排除了不符合纳入标准的文章。我们纳入了128项研究，这些都不是预印本，包括30个国家的127,583名新生儿，包括21个低收入和中等收入国家（LMICs）进行分析。我们发现血流感染是报告数据中最常见的感染类型。我们估计住院新生儿CRKP感染的合并全球患病率为0.3%(95%置信区间[CI],0.2%至0.3%）。根据21项报告患者预后的研究，我们发现新生儿CRKP感染的合并死亡率为22.9%(95%CI,13.0%~32.9%).从GenBank中鉴定出总共535个新生儿CRKP基因组，包括序列阅读存档，其中204个与任何出版物无关。我们将204个基因组与文献综述相结合，以了解物种分布，克隆多样性，和碳青霉烯酶类型。我们确定了新生儿CRKP菌株的146种序列类型（STs），发现ST17，ST11和ST15是3种最常见的谱系。特别是,ST17CRKP在4大洲的8个国家的新生儿中出现。可用于分析碳青霉烯酶的1,592个新生儿CRKP菌株中的绝大多数（75.3％）具有编码金属-β-内酰胺酶的基因，而NDM（新德里金属-β-内酰胺酶）似乎是最常见的碳青霉烯酶（64.3％）。这项研究的主要局限性是缺乏或缺乏来自北美的数据，南美洲,和大洋洲。
结论：CRKP导致相当数量的新生儿感染，并导致显著的新生儿死亡率。新生儿CRKP菌株高度多样化，而ST17在全球流行，值得早期发现用于治疗和预防。blaNDM碳青霉烯酶基因的优势对新生儿的治疗选择提出了挑战，并支持了持续的抑制剂相关药物发现。
结果：我们对报告由CRKP引起的以人群为基础的新生儿感染的研究进行了系统评价，并对所有公开的新生儿来源的CRKP基因组进行了基于基因组的分析。我们搜索了多个数据库(PubMed，WebofScience,Embase,OvidMEDLINE,科克伦,bioRxiv,和medRxiv），以确定报告截至2022年6月30日新生儿CRKP感染数据的研究。我们纳入了新生儿CRKP感染和定植患病率的研究，但排除了缺乏新生儿数量的研究。地理位置,或克雷伯菌或CRKP分离株的独立数据。我们使用JMP统计软件对数据进行叙述性综合。我们确定了8,558篇文章，排除了不符合纳入标准的文章。我们纳入了128项研究，这些都不是预印本，包括30个国家的127,583名新生儿，包括21个低收入和中等收入国家（LMICs）进行分析。我们发现血流感染是报告数据中最常见的感染类型。我们估计住院新生儿CRKP感染的合并全球患病率为0.3%(95%置信区间[CI],0.2%至0.3%）。根据21项报告患者预后的研究，我们发现新生儿CRKP感染的合并死亡率为22.9%(95%CI,13.0%~32.9%).从GenBank中鉴定出总共535个新生儿CRKP基因组，包括序列阅读存档，其中204个与任何出版物无关。我们将204个基因组与文献综述相结合，以了解物种分布，克隆多样性，和碳青霉烯酶类型。我们确定了新生儿CRKP菌株的146种序列类型（STs），发现ST17，ST11和ST15是3种最常见的谱系。特别是,ST17CRKP在4大洲的8个国家的新生儿中出现。可用于分析碳青霉烯酶的1,592个新生儿CRKP菌株中的绝大多数（75.3％）具有编码金属-β-内酰胺酶的基因，而NDM（新德里金属-β-内酰胺酶）似乎是最常见的碳青霉烯酶（64.3％）。这项研究的主要局限性是缺乏或缺乏来自北美的数据，南美洲,和大洋洲。
结论：CRKP导致相当数量的新生儿感染，并导致显著的新生儿死亡率。新生儿CRKP菌株高度多样化，而ST17在全球流行，值得早期发现用于治疗和预防。blaNDM碳青霉烯酶基因的优势对新生儿的治疗选择提出了挑战，并支持了持续的抑制剂相关药物发现。
