Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae
耐碳青霉烯类肺炎克雷伯菌的分子流行病学
基本信息
- 批准号:9098583
- 负责人:
- 金额:$ 23.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-06-25 至 2018-05-31
- 项目状态:已结题
- 来源:
- 关键词:Admission activityAntibiotic ResistanceAntibioticsAntimicrobial ResistanceBacterial Drug ResistanceBiological PreservationCarbapenemsCharacteristicsClinicalClinical MarkersColistinDataDevelopmentEpidemicFundingFutureGenesGeneticGenetic MarkersGenomicsGoalsGreat Lakes RegionHealthHealth Care CostsHealthcare SystemsHospital MortalityHospitalsHumanIn VitroInfectionInstitutesInterventionKlebsiella pneumonia bacteriumLeadershipLength of StayLifeLinkLong-Term CareMapsMeasuresMedical GeneticsMobile Genetic ElementsModelingMolecularMolecular EpidemiologyOrganismOutcomePatient riskPatientsPatternPlasmidsPolysaccharidesPositioning AttributePredispositionPublic HealthRecommendationRecording of previous eventsReportingResistanceResistance developmentResortRiskRisk FactorsStructureSystemTimeToxic effectVariantbasecarbapenem resistancecarbapenem-resistant Enterobacteriaceaeclinical riskcolistin resistanceepidemiologic datafight againstgenetic elementgenetic signaturegenetic variantgenome sequencingin vitro activityindividual patientinterestnovelpathogenpatient stratificationprimary outcomeprospectiveresistant straintherapy designtigecyclinewhole genome
项目摘要
DESCRIPTION (provided by applicant): Antimicrobial resistance is "one of the greatest threats to human health worldwide" and carbapenem-resistant enterobacteriaceae (CRE) represent an immediate public health threat that requires urgent and aggressive action. In the US, infections caused by resistant organisms add $21-$34 billion to healthcare costs annually. Carbapenem-resistant Klebsiella pneumoniae (CRKP) are the most commonly encountered CRE in the US. CRKP are resistant to most antibiotics and clinical outcomes with CRKP infections are generally poor. The globally endemic CRKP strain ST258 is responsible for most CRKP infections in the US. The overarching hypothesis of this R21 proposal is that ST258 strains of CRKP carry specific genes that are associated with poor clinical outcomes and that these genetic elements are nonuniformly distributed among the isolates. Using whole genome sequencing we will seek to identify genetic and clinical markers of poor outcomes and transmissibility by comparison of colonizing isolates versus those that cause infection. We have already determined that ST258 strains from the Great Lakes region can be grouped based on the presence of two plasmids carrying the blaKPC gene. In addition, the two plasmids are associated with distinct chromosomal backgrounds that differ in many genes including those that encode the capsular polysaccharide structure. Finding the links between these observations will help stratify at risk patients by determining which CRKP isolates and what genetic signatures have the most clinical impact. To obtain these answers, we will join our established multicenter CRKP consortium, which currently consists of 9 hospital systems, covering more than 2 million people living in the Great Lakes region with the genomics expertise of JCVI. Since January of 2012, more than 500 unique patients with greater than 750 admissions and over 850 CRKP culture episodes have been included in this consortium; so far, we have analyzed 57 strains by WGS. We have 2 specific aims. 1) To discover molecular characteristics that are associated with clinical outcomes in patients infected with ST258 strains of CRKP. We will determine the genomic sequences of CRKP isolates collected from patients with extensive clinical information, treatment history, and outcome data. The primary outcome of interest will be association of genetic variants with hospital mortality. Secondary measures will include variants associated with post-infection length of stay, ICU admission, and readmissions. 2) To study the interplay between clinical risk factors and molecular characteristics leading to tigecycline and colistin resistance in CRKP isolates. We will determine the mechanisms of resistance of strains with reduced in vitro susceptibility to tigecycline and/or colistin and whethr specific genetic backgrounds in the context of specific clinical settings - such as antibiotic exposure or stay in long term care - are associated with tigecycline and/or colistin resistance. Molecular results combined with clinical/epidemiologic data will inform these models. Our unique approach will provide the necessary understanding that is crucial in the design of interventions to curb the CRKP epidemic.
项目成果
期刊论文数量(5)
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: Trends and Lessons Learned.
- DOI:10.1016/j.idc.2016.02.004
- 发表时间:2016-06
- 期刊:
- 影响因子:4.4
- 作者:van Duin D;Paterson DL
- 通讯作者:Paterson DL
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ROBERT A. BONOMO其他文献
ROBERT A. BONOMO的其他文献
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{{ truncateString('ROBERT A. BONOMO', 18)}}的其他基金
Oral Metallo-Beta-Lactamase Inhibitors: Exploiting Reaction Mechanisms
口服金属-β-内酰胺酶抑制剂:利用反应机制
- 批准号:
10618795 - 财政年份:2021
- 资助金额:
$ 23.55万 - 项目类别:
Veterans Affairs - Translational Education and Mentoring (VA-TEAM) Center
退伍军人事务部 - 转化教育和指导 (VA-TEAM) 中心
- 批准号:
10553091 - 财政年份:2021
- 资助金额:
$ 23.55万 - 项目类别:
Veterans Affairs - Translational Education and Mentoring (VA-TEAM) Center
退伍军人事务部 - 转化教育和指导 (VA-TEAM) 中心
- 批准号:
10231804 - 财政年份:2021
- 资助金额:
$ 23.55万 - 项目类别:
Veterans Affairs - Translational Education and Mentoring (VA-TEAM) Center
退伍军人事务部 - 转化教育和指导 (VA-TEAM) 中心
- 批准号:
10341217 - 财政年份:2021
- 资助金额:
$ 23.55万 - 项目类别:
Oral Metallo-Beta-Lactamase Inhibitors: Exploiting Reaction Mechanisms
口服金属-β-内酰胺酶抑制剂:利用反应机制
- 批准号:
10383142 - 财政年份:2021
- 资助金额:
$ 23.55万 - 项目类别:
Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae
耐碳青霉烯类肺炎克雷伯菌的分子流行病学
- 批准号:
8975488 - 财政年份:2015
- 资助金额:
$ 23.55万 - 项目类别:
The Continuing Challenge of Carbapenemases in K. pneumoniae: KPC-2 & NDM-1
肺炎克雷伯菌中碳青霉烯酶的持续挑战:KPC-2
- 批准号:
8441988 - 财政年份:2013
- 资助金额:
$ 23.55万 - 项目类别:
The Continuing Challenge of Carbapenemases in K. pneumoniae: KPC-2 & NDM-1
肺炎克雷伯菌中碳青霉烯酶的持续挑战:KPC-2
- 批准号:
10620247 - 财政年份:2013
- 资助金额:
$ 23.55万 - 项目类别:
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