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Title [sv]
Kombination av metabolmik och genomik för att diagnostisera och förstå blodinfektioner orsakade av antibiotikaresistenta bakterier i låginkomstländer
Title [en]
Combining metabolomics and genomics to develop new approaches for diagnosing and understanding bloodstream infections caused by antimicrobial resistant bacteria in low-income setting
Abstract [en]
Bloodstream infections (BSIs) caused by bacterial pathogens are a leading healthcare problem worldwide and a common cause of morbidity and mortality even in the countries with advanced healthcare systems. Treating the BSIs often demands intensive care measures including artificial ventilation and blood dialysis during such complications as multiple organ failure. The negative impact of BSI is especially pronounced in the low-income countries where the quality of the healthcare may be not capable of handling critically ill patients and/or the number of hospitals and their location is disproportional to demographic needs. Additionally, BSIs combined with antimicrobial resistance (AMR) constitute a particularly difficult problem to tackle. The infection develops quickly, the choice of effective therapies is limited and the process of selecting an appropriate treatment is slow as it involves the isolation of the etiologic agent. In case of multi-AMR of the pathogen, and lack of effective antimicrobials, medical professionals may have to fight the severe infection virtually unarmed with only empiric therapies. The grave scenario of returning to the pre-antimicrobial era is looming, and there are limited data regarding the epidemiology of AMR and BSI in low-income countries. Further, diagnostic methods for BSI are currently slow, ineffective and push healthcare personnel to administrate empirical treatment that may be not beneficial for the patient and may drive the AMR globally even further. Considering the urgent global challenges associated with AMR and BSIs, the aims of our study are:1.To investigate the burden and clinical epidemiology of BSI in a tertiary hospital in Vietnam, a lower-middle income country with a population of 90.6 million. The identification and characterization of the bacteria causing BSI will be performed in the context of AMR (using whole genome sequencing). The influence of AMR and the type of infecting pathogen on the disease outcome will be analyzed.2.To determine species specific and AMR metabolite signatures of bacteria causing BSIs. This will be performed in both blood samples from subjects with BSI and in bacterial cultures of AMR pathogens with distinct genetic backgrounds. Metabolomics data from clinical samples will be integrated with the corresponding data from genomic sequencing to produce reliable markers of AMR/BSI.3.To develop a rapid diagnostic approach for the analysis of metabolite signatures of AMR/BSI in dry blood samples. Such samples can be quickly shipped from remote areas to the bigger health centers/laboratories and we aim to analyze the efficiency and the impact of such diagnostic strategy in low-income settings in Vietnam. To achieve the identified aims we will combine cutting-edge methods as next generation bacterial genome sequencing and highly sensitive metabolite analysis with clinical data and advanced bioinformatics. Statistical significance will be secured through recruiting of 7,000 participants in this study and we aim to sequence 1,000 clinically relevant bacterial genomes. This consortium is established for the project as partner Baker has extensive documented experience of microbiological/clinical investigations in Asian settings and applicant Antti is a field leader in metabolomics studies in infectious diseases. The applicants have a record of joint work and publication indicating successful communication and efficient collaboration of these groups. The expected impact of the study is highly significant. Within the four-year duration of the project we will have a detailed understanding of the epidemiology and genomics of AMR/BSI in a major hospital in Vietnam, a country heavily affected by AMR. The key factors for the propagation of AMR pathogens in Vietnam will be identified with the potential to extrapolate the results to other parts of Asia. The proposed approach for AMR/BSI testing by metabolite signatures will be designed, validated and may potentially d
Principal InvestigatorAntti, Henrik
Coordinating organisation
Umeå University
Funder
Period
2016-01-01 － 2018-12-31
National Category
Analytical ChemistryMicrobiology in the medical areaInfectious Medicine
Identifiers
DiVA, id: project:1493Project, id: 2015-03442_VR
v. 2.47.0
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