Bacterial Characteristics of Community-associated Carbapenem-Resistant Enterobacteriaceae
群落相关碳青霉烯类耐药肠杆菌科细菌的特征
基本信息
- 批准号:10549351
- 负责人:
- 金额:$ 38.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-13 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:Active SitesAntibioticsArgentinaAustraliaBacterial Drug ResistanceBiologicalBiological AssayCarbapenemsCell AdhesionCell LineCellsCensusesCharacteristicsChileChinaClinicalClostridium difficileColombiaCommunitiesCommunity HospitalsDataDiagnosisEarly identificationEnrollmentEnterobacteriaceaeEnterobacteriaceae InfectionsEpidemiologyEvaluationExtended-spectrum β-lactamaseFundingGene ClusterGene ExpressionGene FamilyGenesGeneticGenomeHealth Care CostsHealth care facilityHealthcareHealthcare SystemsHomeHospitalizationHospitalsHumanIn VitroInfectionInfrastructureInternationalIntestinesKlebsiellaLeadershipLong-Term CareMeasuresMobile Genetic ElementsModelingMolecular EpidemiologyMorbidity - disease rateMusNew ZealandNicaraguaOutcomePathway interactionsPatient AdmissionPatientsPersonsPhenotypePlasmidsPublic HealthRecording of previous eventsResistanceSingaporeSiteStaphylococcus aureusWorkacute careantimicrobialbacterial geneticscarbapenem resistancecarbapenem-resistant Enterobacteriaceaecarbapenemasecommunity settingcommunity transmissiondysbiosisgenetic analysisgenome analysisgenome sequencinggut colonizationhealthcare-associated infectionshigh riskhuman microbiotaindexinginterestmethicillin resistant Staphylococcus aureusmortalitymulti-drug resistant pathogenoverexpressionpressurepreventprospectiveresponsetransmission processtype 1 fimbriaewhole genome
项目摘要
Carbapenem-resistant Enterobacteriaceae (CRE) represent an immediate public health threat that requires
urgent and aggressive action. To date, most CRE infections are healthcare associated (HA). However, the
molecular epidemiology of other multidrug resistant organisms (MDRO) such as methicillin-resistant
Staphylococcus aureus (MRSA) and Clostridium difficile suggests that progression to community-associated
(CA) CRE is an imminent threat. Early recognition of potential CA-CRE strains and a clear biological
understanding of mechanisms resulting in community transmission is essential for an appropriate response.
The Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE)
is a prospective, international, multicenter, observational ongoing study for which Dr. van Duin is the PI.
CRACKLE is federally funded through and data-shares with the Antibacterial Resistance Leadership Group
(ARLG). In CRACKLE, all patients at participating hospitals who have CRE isolated from a clinical culture
during hospitalization are included. Our preliminary data from CRACKLE indicate an increase in the US in
possible CA-CRE infections. Our overall hypothesis is that enhanced intestinal colonization is a final common
pathway for community spread of CRE strains that are responsible for increasing CA-CRE infections in the US.
Enhanced ability to establish intestinal colonization, especially in the absence of antimicrobial-induced
dysbiosis is proposed to be a prerequisite for successful community spread of CRE. In line with this
hypothesis, our preliminary data shows a relative lack of fimE in CRE from patients admitted from home
without obvious healthcare exposures. Absence of fimE results in over-expression of type 1 fimbriae, which
are known to be involved in intestinal colonization. In this proposal, we will use CRACKLE infrastructure to
evaluate current CA-CRE infections in the US and study CRE spread in the community (Aim 1). The intestinal
colonization potential of various CRE strains will be determined in human intestinal cell adhesion and murine
intestinal colonization assays with increasing antibiotic pressures (Aim 2). Finally, we will determine which
bacterial chromosomal and/or plasmid genetic characteristics are associated with the CA-CRE phenotype, by
performing whole genome analysis and plasmid analysis (Aim 3). This genetic analysis will focus on gene
families that are known to play a role in intestinal colonization such as fim. Together, these studies will allow
for early discovery of CRE strains and/or carbapenemase gene-carrying plasmids with potential for community
spread resulting in guided efforts to prevent widespread community dissemination of CRE.
耐碳青霉烯肠杆菌科(CRE)是一种迫在眉睫的公共卫生威胁
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multidrug-Resistant Bacteria in the Community: An Update.
- DOI:10.1016/j.idc.2020.08.002
- 发表时间:2020-12
- 期刊:
- 影响因子:4.4
- 作者:van Duin D;Paterson DL
- 通讯作者:Paterson DL
Carbapenemase-producing organisms in solid organ transplantation.
实体器官移植中产生碳青霉烯酶的微生物。
- DOI:10.1097/mot.0000000000000664
- 发表时间:2019
- 期刊:
- 影响因子:2.2
- 作者:Wong,Darren;vanDuin,David
- 通讯作者:vanDuin,David
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DAVID VAN DUIN其他文献
DAVID VAN DUIN的其他文献
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{{ truncateString('DAVID VAN DUIN', 18)}}的其他基金
Bacterial Characteristics of Community-associated Carbapenem-Resistant Enterobacteriaceae
群落相关碳青霉烯类耐药肠杆菌科细菌的特征
- 批准号:
10328871 - 财政年份:2019
- 资助金额:
$ 38.12万 - 项目类别:
Dectin-IL-17 axis, candidemia, and aging
Dectin-IL-17 轴、念珠菌血症和衰老
- 批准号:
8324518 - 财政年份:2011
- 资助金额:
$ 38.12万 - 项目类别:
Dectin-IL-17 axis, candidemia, and aging
Dectin-IL-17 轴、念珠菌血症和衰老
- 批准号:
8184779 - 财政年份:2011
- 资助金额:
$ 38.12万 - 项目类别:
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