EARLY ACQUISITION AND CARRIAGE OF GENETICALLY DIVERSE MULTI-DRUG RESISTANT GRAM-NEGATIVE BACILLI IN HOSPITALISED SMALL VULNERABLE NEWBORNS IN THE GAMBIA
EARLY ACQUISITION AND CARRIAGE OF GENETICALLY DIVERSE MULTI-DRUG RESISTANT GRAM-NEGATIVE BACILLI IN HOSPITALISED SMALL VULNERABLE NEWBORNS IN THE GAMBIA
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冈比亚住院的小弱势新生儿早期获得和携带基因多样化的多重耐药革兰氏阴性杆菌
DOI：
10.1101/2022.11.16.22282268
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Bah S
中科院分区：
文献类型：
--
作者：
Bah S
AimThis详细的基因组研究的目的是在一个低资源的非洲hospital.MethodsThis横断面队列研究进行了在唯一的新生儿转介单位在冈比亚与MRC单位冈比亚在LSHTM的基因组分析，在小脆弱的新生儿和他们配对的母亲，多药耐药革兰氏阴性杆菌（MDR-GNB）肠道和皮肤运输。<2kg的新生儿每周接受皮肤和肛周运输拭子采样，并配对母体直肠阴道拭子。使用麦康凯琼脂进行前瞻性细菌学培养，通过API 20 E和API 20 NE进行菌种鉴定。所有GNB分离株在Illumina Miseq平台上进行全基因组测序。结果从34例新生儿和21对母亲（21对母子）共采集135份携带拭子，共分离出137株GNB，其中112株为高质量的重组株。新生儿MDR-GNB皮肤或肠道携带患病率为41%（14/34），入院时85%（11/13）的新收购发生在7天。新生儿在不同时间点携带多种MDR和ESBL-GNB，以K. pneumoniae和E.大肠杆菌，具有异质性菌株多样性，没有克隆性的证据和111个不同的抗生素抗性基因，主要是β-内酰胺类（Bla-AMPH，Bla-PBP，CTX-M-15，Bla-TEM-105）。76%（16/21）和62%（13/21）的母亲直肠阴道携带至少1种MDR-GNB和ESBL-GNB，最常见的是MDR-E。大肠杆菌（76%，16/21）和MDR-K.肺炎（24%，5/21）。在21对新生儿-母亲二元组中，只有一对具有基因相同的分离株（E。coliST 131和K.结论冈比亚住院的矮小脆弱新生儿在出生后7天内具有较高的MDR和ESBL-GNB携带率。母亲和新生儿之间的异质性菌株多样性和缺乏匹配的分离株表明多种环境来源可能在传播中很重要。在类似的资源有限的环境中进行更大规模的基因组研究以确认这些发现，是为有针对性的监测和感染预防控制政策提供信息的基础。-MDR-GNB，特别是肺炎克雷伯氏菌和大肠杆菌，是非洲新生儿侵袭性感染和死亡的重要原因，被世卫组织列为研究的高度优先病原体-新生儿MDR-GNB携带是侵袭性感染的先兆，早产，低出生体重儿（“脆弱的小新生儿”）风险最大-在欧洲和其他国家，母亲携带耐多药GNB是新生儿病原体获得的一个风险因素，本研究补充了：-住院的冈比亚小型脆弱新生儿具有较高的MDR和ESBL-GNB携带率，在出生和7天之间获得-K的异质性多样性。pneumoniae和E.大肠杆菌菌株表明多个环境来源，没有克隆爆发的证据-β-内酰胺酶基因最常被鉴定为高ESBL和AMP-C基因产生率-尽管母亲MDR-GNB携带率高，但没有基因组证据表明母亲向新生儿广泛传播
AimThis detailed genomic study aimed to characterise multi-drug resistant-gram negative bacilli (MDR-GNB) intestinal and skin carriage in small vulnerable newborns and their paired mothers at a low-resource African hospital.MethodsThis cross-sectional cohort study was conducted at the only neonatal referral unit in The Gambia with genomic analysis at MRC Unit The Gambia at LSHTM. Neonates <2kg underwent skin and peri-anal carriage swab sampling weekly with paired maternal rectovaginal swabs. Prospective bacteriological culture used MacConkey agar with species identification by API20E and API20NE. All GNB isolates underwent whole genome sequencing on Illumina Miseq platform. Multi-Locus Sequence Typing and SNP-distance analysis were used to identify strain type and infer relatedness.Findings135 carriage swabs were obtained from 34 neonates and 21 paired mothers (21 neonate-mother dyads), yielding 137 GNB isolates of which 112 were high quality de novo assemblies. Neonatal MDR-GNB skin or intestinal carriage prevalence was 41% (14/34) at admission with 85% (11/13) new acquisition occurring by 7 days. Multiple MDR and ESBL - GNB species were carried by neonates at different timepoints, most frequentlyK. pneumoniaeandE. coli, with heterogeneous strain diversity, no evidence of clonality and 111 distinct antibiotic resistance genes, mostly Beta-Lactams (Bla-AMPH,Bla-PBP, CTX-M-15,Bla-TEM-105). 76% (16/21) and 62% (13/21) of mothers had recto-vaginal carriage of at least 1MDR-GNB and ESBL-GNB respectively, most commonly MDR-E. coli (76%, 16/21) and MDR-K. pneumoniae(24%, 5/21). Of 21 neonate-mother dyads only one had genetically identical isolates (E. coliST131 andK. pneumoniaeST3476).ConclusionGambian hospitalised small vulnerable neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7 days. The heterogeneous strain diversity and lack of matching isolates between mothers and newborns suggests multiple environmental sources may be important in transmission. Larger genomic studies to confirm these findings in similar resource limited settings is foundational to inform targeted surveillance and infection prevention control policies.What is known:-MDR-GNB, especiallyKlebsiella pneumoniaeandEscherichia coli, are important causes of neonatal invasive infections and mortality in Africa, classified by WHO as pathogens of high priority for research-Neonatal MDR-GNB carriage is a pre-curser for invasive infection, with preterm, low-birth weight neonates (“Small Vulnerable Newborns”) at greatest risk-Maternal MDR-GNB carriage is a risk factor for neonatal pathogen acquisition in Europe and other well-resourced settings, but a priority evidence gap exists for transmission pathways for small vulnerable African newbornsWhat this study adds:-Hospitalised Gambian small vulnerable neonates have high carriage prevalence of MDR- and ESBL-GNB with acquisition occurring between birth and 7 days-Heterogeneous diversity ofK. pneumoniaeandE. colistrains suggests multiple environmental sources with no evidence of clonal outbreak-Beta-lactamase genes were most commonly identified with high rates of ESBL- and AMP-C gene production-Despite high maternal MDR-GNB carriage prevalence there is no genomic evidence indicating widespread transmission from mother to newborn
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影响因子：
8.4
作者：
Dramowski, A.;Aucamp, M.;Mehtar, S.
通讯作者：
Mehtar, S.
影响因子：
5.2
作者：
Li, Grace;Bielicki, Julia Anna;Sharland, Michael
通讯作者：
Sharland, Michael
某妇产医院发生粘质沙雷氏菌院内暴发的调查
DOI：
--
发表时间：
1999
期刊：
Infection Control & Hospital Epidemiology
影响因子：
--
作者：
P. Berthelot;F. Grattard;Colette Amerger;Marie;F. Lucht;B. Pozzetto;Philippe Fargier
通讯作者：
Philippe Fargier
影响因子：
4.2
作者：
Labi, Appiah-Korang;Bjerrum, Stephanie;Kurtzhals, Jorgen A. L.
通讯作者：
Kurtzhals, Jorgen A. L.
影响因子：
28.3
作者：
Sands K;Carvalho MJ;Portal E;Thomson K;Dyer C;Akpulu C;Andrews R;Ferreira A;Gillespie D;Hender T;Hood K;Mathias J;Milton R;Nieto M;Taiyari K;Chan GJ;Bekele D;Solomon S;Basu S;Chattopadhyay P;Mukherjee S;Iregbu K;Modibbo F;Uwaezuoke S;Zahra R;Shirazi H;Muhammad A;Mazarati JB;Rucogoza A;Gaju L;Mehtar S;Bulabula ANH;Whitelaw A;BARNARDS Group;Walsh TR
通讯作者：
Walsh TR