Decoding the clinical impact of the recent evolution of metronidazole resistance on Clostridium difficile infection
解读甲硝唑耐药性的最新演变对艰难梭菌感染的临床影响
基本信息
- 批准号:10215475
- 负责人:
- 金额:$ 67.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-20 至 2023-02-21
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAffectAnaerobic BacteriaAnimalsBypassCenters for Disease Control and Prevention (U.S.)Cessation of lifeClinicalClinical TrialsClostridium difficileColonComplementComplexDNA Sequence AlterationDataDetectionDrug PrescriptionsEnvironmentEpidemicEvolutionFecesGenesGeneticGenetic ProgrammingGenotypeGuideline AdherenceHamstersHealthcareHemeHumanIn VitroIncidenceInfectionIntestinesIronLightMedicalMedical centerMetabolismMetadataMetronidazoleMetronidazole resistanceModelingMolecularMolecular GeneticsMutagenesisMutateMutationOutcomeOxidative StressOxidoreductasePathogenesisPathway interactionsPatient IsolatorsPatientsPharmaceutical PreparationsPhenotypePhysiologicalPractice GuidelinesPredispositionPublic HealthRefractoryResearchResistanceRibotypesSavingsSeveritiesSubgroupSulfurTestingTexasTreatment outcomeUnited StatesValidationabsorptionanalogantibiotic-associated diarrheabiobankclinically significantcofactordynamical evolutiongene functiongenetic resistancegenome wide association studygenomic dataimprovedinfection managementmutantpressurepreventresistance generesistant strainresponsesugartrend
项目摘要
PROJECT SUMMARY/ABSTRACT
Clostridium difficile is the main cause of antibiotic-associated diarrhea. Since 2003, the incidence and severity
of C. difficile infection (CDI) has risen in the U.S. and globally. In 2013 the CDC designated C. difficile as an
Urgent Threat, which caused ~29,000 deaths from ~453,000 cases in 2011. These trends were related to the
emergence of epidemic strains, particularly epidemic 027. Epidemic 027 causes about a third of CDI in the
U.S. Metronidazole is the most commonly prescribed drug for CDI, but after 30 years of use, it is now
associated with poorer treatment outcomes. Reasons for the now poorer outcomes for metronidazole therapy
is unclear. A subset of epidemic 027 strains show decreased susceptibility to metronidazole, when tested in
the cofactor heme. Similarly, other dominant epidemic strains associated with CDI in the United States have
evolved metronidazole resistance that is expressed in heme. While resistance has evolved in clinical strains, it
is unclear how this impacts the ability to treat CDI with metronidazole. This study addresses this medically
important question, by investigating how metronidazole resistance affects treatment outcomes. Firstly, a
biobank of patient stools is examined for metronidazole-resistant strains, heme levels and patient metadata for
clinical outcomes. This plan is complemented by experimental CDI models, namely the in vitro human gut and
hamster models of CDI that are clinically reflective. Also addressed is the question of whether the low
concentrations of metronidazole in the colon of patients is inadequate to treat infections with metronidazole-
resistant strains. The genetic mechanisms adopted by C. difficile to display resistance is still unclear. Hence,
this study elucidates the genetic basis for the evolution of metronidazole resistance in C. difficile, using a
combination of cutting-edge genetic algorithms to identify gene changes in the genomic data sets for resistant
isolates when compared to sensitive isolates and by molecular genetics to recapitulate metronidazole
resistance in naïve strains. Public health. The successful completion of this study will immediately impact
healthcare practices and the guidelines for CDI management. This could save lives by improving prescribing
practices and guideline adherence.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Julian G Hurdle其他文献
Mechanisms and impact of antimicrobial resistance in emClostridioides difficile/em
艰难梭菌中抗菌药物耐药性的机制和影响
- DOI:
10.1016/j.mib.2022.01.004 - 发表时间:
2022-04-01 - 期刊:
- 影响因子:7.500
- 作者:
Chetna Dureja;Abiola O Olaitan;Julian G Hurdle - 通讯作者:
Julian G Hurdle
Julian G Hurdle的其他文献
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{{ truncateString('Julian G Hurdle', 18)}}的其他基金
Mechanism Of Enterococcus Faecalis Nitro Drug Metabolism And In Vivo Implications
粪肠球菌硝基药物代谢机制及其体内影响
- 批准号:
10511022 - 财政年份:2022
- 资助金额:
$ 67.51万 - 项目类别:
Mechanism Of Enterococcus Faecalis Nitro Drug Metabolism And In Vivo Implications
粪肠球菌硝基药物代谢机制及其体内影响
- 批准号:
10634708 - 财政年份:2022
- 资助金额:
$ 67.51万 - 项目类别:
High Throughput Screening for Non-antibiotic inhibitors of Clostridium difficile Pathophysiology
高通量筛选艰难梭菌病理生理学的非抗生素抑制剂
- 批准号:
10335182 - 财政年份:2019
- 资助金额:
$ 67.51万 - 项目类别:
Decoding the clinical impact of the recent evolution of metronidazole resistance on Clostridium difficile infection
解读甲硝唑耐药性的最新演变对艰难梭菌感染的临床影响
- 批准号:
9767021 - 财政年份:2018
- 资助金额:
$ 67.51万 - 项目类别:
Relationships Among Metronidazole Resistance, Pharmacodynamics and Treatment Outcomes in Clostridium difficile Infection
艰难梭菌感染甲硝唑耐药性、药效学和治疗结果之间的关系
- 批准号:
9526756 - 财政年份:2017
- 资助金额:
$ 67.51万 - 项目类别:
Nature inspired treatments for persistent C. difficile infections
针对持续性艰难梭菌感染的自然疗法
- 批准号:
9002293 - 财政年份:2011
- 资助金额:
$ 67.51万 - 项目类别:
Nature inspired treatments for persistent C. difficile infections
针对持续性艰难梭菌感染的自然疗法
- 批准号:
8298513 - 财政年份:2011
- 资助金额:
$ 67.51万 - 项目类别:
Nature inspired treatments for persistent C. difficile infections
针对持续性艰难梭菌感染的自然疗法
- 批准号:
8496728 - 财政年份:2011
- 资助金额:
$ 67.51万 - 项目类别:
Nature inspired treatments for persistent C. difficile infections
针对持续性艰难梭菌感染的自然疗法
- 批准号:
8161695 - 财政年份:2011
- 资助金额:
$ 67.51万 - 项目类别:
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