The proportion of patients requiring adapted treatment with reserve antibiotics due to resistant bacteria in hospitals is increasing worldwide. This is because many of the multidrug-resistant pathogens are often not detected by the initial antibiotic therapies recommended in guidelines. In severe infections, such as sepsis, lethality increases with each hour that adequate therapy is delayed. However, routine culture-based diagnostics provide definitive results only on day 3-4 after sample collection. With molecular testing and point-of-care (PoC) diagnostics, results can be available within hours and therapy for critically ill patients can be adjusted so quickly.
In interdisciplinary collaboration with industry partners and other research institutions from Jena and throughout Germany, we are developing various approaches for faster and targeted diagnostics of increasingly problematic resistances. This interdisciplinary collaboration is supported in Jena by federal, state and EU research networks such as InfectoOptics, InfectoGnostics and InfectControl2020 , in which we are involved in various research and development (R&D) projects.
Current Projects
PbR
Development of a modular multiplex detection system for plasmid-based antibiotic resistance monitoring
Further information can be found here: PLASMID-BASIERTE RESISTENZNACHWEIS
Project period: 01.10.2018- 31.08.20212
Collaborative partners: SIOS Meßtechnik GmbH, (coordinator), Leibniz-Institut für Photonische Technologien e.V. , Mildendo GmbH
The project is funded by the Free State of Thuringia and co-financed by funds of the European Union within the framework of the European Regional Development Fund (ERDF) under the funding code 2018 FE 9038 (Vebundsnummer 2018 VF0015).
MultiHoloDiag
Multiparameter analysis with optical holographic methods for medical diagnostics
For further information please click here:MULTI HOLO DIAG
Project period: 01.01.2019- 31.12.2021
Collaborative partners: Leibniz-Institut für Photonische Technologien e.V. (coordinator), Center for Sepsis Care and Control (CSCC),
The project is funded by the Free State of Thuringia with money from the European Social Fund (ESF) under the funding code 2018 FGR 0095.
PREPLEX
AI-assisted assay development for phenotypic carbapenem resistance by porin loss and efflux overexpression in Gram-negative bacteria
More information can be found here: PREPLEX und im PREPLEX-Video
Project period: 01.09.2020- 31.08.2025
Collaborative partners: Curetis GmbH, Ares Genetics GmbH
Carbapenem resistance in Gram-negative bacteria is one of the greatest challenges for therapy and diagnostics. However, a carbapenem-resistant phenotype is not always due to a carbapenemase, an enzyme that inactivates the reserve antibiotics. Often, this phenotype is caused by secondary mechanisms, such as porin loss or increased efflux, which can be well treated with targeted combination therapies. However, culture-based routine diagnostics do not differentiate the genotype and phenotype, whereas classical PCR-based molecular diagnostics only detect the genotype. However, the phenotype is always genetically encoded, so it would have to be theoretically derived from the genome, but this would have to take into account highly complex regulatory mechanisms and countless genes and even more allelic variants. This can hardly be understood by simple methods. Therefore, deep-learning processes will be applied to infer phenotypes from genome data. In this context, molecular markers will also be identified that, in simple mRNA-based assays, differentiate a non-carbapenemase-related carbapenem resistance phenotype.
The project is carried out within the framework of the research campus InfectoGnostics and is funded by the German Federal Ministry of Education and Research under grant number 13GW0457A.
DRESI
Rapid and precise diagnostics and resistance testing of sepsis pathogens in intensive care units
Project period: 01.03.2020- 28.02.203
Collaborative partners: BLINK AG, Leibniz-Institut für Photonische Technologien e. V. Jena
The mortality associated with sepsis is about 42% in Germany and could hardly be reduced in the past. An important factor for sepsis-related death is still the lack of detection of the causative pathogen and its resistance factors. Simplification of today's extremely challenging preanalytics and analytics for pathogen diagnostics and resistance determination offers a realistic opportunity to reduce mortality in patients with suspected sepsis and to implement effective antibiotic therapy management mechanisms directly in the ICU.
The project aims to explore a novel test that allows sensitive detection of all relevant pathogens and their resistance factors within 30 minutes from the patient sample in the ICU and couples it with expert advice via integrated connectivity. The test is intended to be modular and thus easily expandable to include new pathogens and resistance markers.
This will create an essential prerequisite for optimal therapy management of critically ill patients and enable the rational use of antibiotics.
Funded by the German Federal Ministry of Education and Research under grant number 13GW0423B.
Development of a multiplex approach for the detection of antibiotic resistance in gram-negative bacteria with a focus on the detection of individual phenotype-determining substituents
GenID-ARRAY
Project period: 01.09.2019- 31.08.2022
Collaborative partners: Autoimmin Diagnostica GmbH / GenID GmbH
In the last decade, the situation of multi-resistant gram-negative pathogens (MRGN) in particular has become more acute: In some European countries, already more than 50% of all nosocomial infections with gram-negative bacteria are caused by so-called ESBL (extended spectrum β-lactamase) formers, which degrade the third-generation cephalosporins recommended for treatment. Such ESBL-formers may additionally be resistant to other empirically applied antibiotics, such as fluoroquinolones (FQ) (so-called 3MRGN). This development results in a steep increase in the consumption of carbapenems, the so-called reserve antibiotics, which increasingly have to be used already for the treatment of mild infections due to the resistance of the pathogens. This in turn promotes the selection of carbapenemase-forming bacteria, which are then mostly resistant to all common antibiotics (so-called 4MRGN), which drastically limits treatment options. The β-lactamases represent a highly variable group of enzymes, with diverse phylogenetic lineages that are poorly related to each other and within these with subgroups and numerous allelic variants. Often single point mutations determine the ESBL or carbapenemase phenotype, which classical molecular assays do not differentiate. The aim of the joint project is the development of a solid-phase coupled array for the detection and differentiation before relevant β-lactamases or the phenotype-relevant substitutions in TEM and SHV genes as well as the QRDR (quinolone resistance determining regions) by means of a single base addition with fluorescent nucleotides in a multiplex approach.
Funded by the German Federal Ministry for Economic Affairs and Energy as part of the Central Innovation Program for SMEs (ZIM) under the funding code ZF4727701NK9.