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Projects

B-FAST: Nationwide Research Network Applied Surveillance and Testing on Covid-19

WP 3.3

Developing an integrated testing and surveillance strategy platform for different settings, such as the general population, schools and daycare centers, high-risk areas, and clinics.

The network's collaborative assessments of testing methods and joint development and evaluation of surveillance approaches will help to develop surveillance and testing strategies that are sustainable, scalable, and transferable to future pandemics.

Contact: Grundmann, H

Projectstart: 01.09.2020

Projektend: 31.12.2021

Work package leader: Grundmann, H


K-STaR: a K-mer-based method for institutional AMF surveillance, infection control and rapid diagnostics.

The aim is to develop a new k-mer based approach for rapid identification of pathogens and possible transmission events within the JPI-EC-AMR Joint Transnational Call "Diagnostics and surveillance of antimicrobial resistance: development of tools, technologies and methods for global use". The main focus is on the development of relevant databases and a methodology that makes identification faster. A sequencer that can be used close to the patient will also contribute to this. The possibility to read antibiotic resistance from the obtained data is also given.

Contact: Grundmann, H; Reuter, S

Projectstart: 01.04.2020

Projectend: 31.03.2023

Projectleader: Grundmann, H


NeWIS: National health care infrastructures, health care utilization and patient movements between hospitals: Networks working to improve surveillance

Projektbeschreibung: There is a worldwide concern about the emergence, and widespread dissemination, of AMR “high-risk” clones that carry the genomic determinants for enhanced virulence and resistance. Regional, national and international surveillance is considered an important component in a strategy to control these strains. However, current surveillance systems are not fit for this purpose and there is still no good evidence base for deciding which and how many sentinel hospitals should be included in surveillance programs. Previous work coordinated by the lead applicant has shown that AMR “high-risk” clones spread between health care institutions as a result of patient movements. Hospitals thus become connected by patients. Taken together, all connections create a nexus of institutions that can be described as national health care referral networks. Despite their apparent complexity, these networks reveal a simple scaffolding and remarkably consistent properties that lie at the core of national health care infrastructures. These show many of the typical hallmarks of hierarchically distributed networks, with regionality, centrality, scale-freeness and small world properties. Hence a quantitative understanding of the network dynamics offers the means for purpose-designed surveillance and better targeted interventions. The current proposal will bring together a critical mass of public health microbiologists, health systems researchers, and social network analysts from Europe and beyond. These experts shall define the data needs, data sources, algorithms and analysis tools with the aim to identify a heuristic optimization approach to sentinel site selection. In this way the suggested project will provide recommendations for the development of surveillance structures that are more parsimonious, cost- and time effective and provide—through the selection of sampling sites for genomic surveillance by whole genome sequencing (WGS)—the genetic signatures for early, next generation diagnostics of recently emerging clones. The focus on site selection means that WGS will not be part of this initiative.

NeWis

Contact: Grundmann H, Donker T

Projectstart: 01.04.2019

Projectend: 31.12.2021

Projectleader: Grundmann H


SafeNet

SafeNet - Digital network as early warning system against risk pathogens

Patient Safety Initiative Baden-Württemberg

For further information please click on the logo.

Contact:  Bürkin, F; Hertweck, S.

Projectstart: 07.07.2020

Projectend: 06.07.2022

Projectleader: Grundmann, H


COMBACTE‐CARE - Combatting Bacterial Resistance in Europe – Carbapenem Resistance

Projektbeschreibung: The objective of the COMBACTE‐CARE project is to understand how patients with carbapenemase‐resistant infections are managed with a focus on best available treatment and clinical outcomes to inform limited population development programmes. Also the project will deliver important clinical and safety data, to support the global development of Aztreonam‐Avibactam (ATM‐AVI) for the treatment of serious bacterial infections caused by multi‐drug resistant (MDR) bacteria expressing a certain type of carbapenemase, a metallo‐β‐lactamase (MBL).

Contact: Reuter S

Projectstart: 01.04.2015

Projectend: 31.07.2021

Projectleader: Grundmann H


NoSPREAD - Preventing the Spread of MDRO

Projektbeschreibung: Das Projekt NoSPREAD widmet sich in einem translationalen Ansatz unter Verwendung sowohl mikrobiologischer Routinedaten als auch moderner Ganzgenom-Sequenziertechnologie der Entwicklung, Validierung sowie Implementierung eines Computer-assistierten Frühwarnsystems zur frühzeitigen Entdeckung von potentiellen nosokomialen Übertragungen und Ausbrüchen bakterieller Erreger. Hiermit wird eine unmittelbare krankenhaushygiensche Intervention ermöglicht, mit der eine rasche Ausbruchskontrolle ermöglicht und eine weitere Ausbreitung insbesondere von hoch-resistenten nosokomialen Infektionserregern (sog. High-risk Clones) verhindert wird. Mit diesem Outbreak Detection Tool soll die Zahl und Größe nosokomialer Ausbrüche vermindert und damit der Verbreitung hochresistenter Mikroorganismen begegnet werden. Nach Implementierung des Outbreak Detection Tool an den beiden DZIF Standorten Berlin und Köln soll es nun an zwei weiteren DZIF-Standorten etabliert werden.

Contact: Bürkin, F

Projectstart: 01.01.2019

Projectend: 31.12.2021

Projectleader: Grundmann H


In-vitro synergistic activity of avibactam-ceftazidime in combination with five other antibiotics against carbapenemase-producing Klebsiella pneumoniae

Projektbeschreibung: Severe infections caused by CPE are usually treated with a combination of two or even more potentially active antibiotics. In fact, in the published case studies, about half the patients treated with ceftazidime-avibactam had received at least one additional antibiotic (see e.g. Shields et al., Clin Infect. Dis, 2016, 63:1615-1618; Temkin et al., Antimicrob Agents Chemother, Epub Jan 2017; Kling et al., Antimicrob Ag Chemother, Epub Mai 2017). Since the patient populations and the infection types were very divergent in these case studies, it cannot be inferred with certainty which combination was the most effective. A combination of antibiotics is expected to be more effective if there was a synetgistic effect between the partners. Therefore, our objective is to examine whether a synergistic effect exists between ceftazidime-avibactam and other antibiotics, e.g., colistin, tigecycline, fosfomycin, gentamycin and amikacin. In this study, whole genome sequencing (WGS) will be used for investigating the emergence and dissemination of resistance genes within the collected representative population of K. pneumoniae. WGS data will be compared with existing resistance gene data bases in order to determine the origin of the isolates.

Ansprechpartner: Grundmann H 

Projektbeginn: 2019

Projektende: 2019

Projektleitung: Grundmann H


CLAR: Etablishing the outbreak detection tool Cluster Alert System

Projektbeschreibung: The project TARGETSPREAD focuses on new technologies to support infection control in hospital settings. A tool developed at partener site Berlin is called Cluster Alert System (CLAR) and is a computer-based outbreak detection tool with already establish algorithms to detect low-level outbreaks and outbreaks on different wards with the same pathogen. In 2017, CLAR was successfully established at the University Hospital Cologne. The aim is to establish CLAR at two more DZIF partner sites.

Contact:  Bürkin, F

Projectstart: 01.02.2019

Projectend: 31.01.2020

Projectleader: Grundmann H


GIF: A multicenter study of the evolution and spread of NDM-producing bacteria across bacterial clones and species

Projektbeschreibung:

Abstract A multicenter study of the evolution and spread of NDM-producing bacteria across bacterial clones and species Background: The carbapenemases are β-lactamase enzymes that confer resistance to all of the β-lactam antimicrobial classes, including carbapenems, the "agents of last resort". Hence, carbapenemase-producing Enterobacteriaceae (CPE) are a critical threat to public health worldwide. Carbapenemase genes may disseminate either by spread of an epidemic bacterial clone or via horizontal transfer of the gene between different bacteria of the same phylogenetic family (e.g., Enterobacteriaceae). The carbapenemase NDM is one of the most common worldwide, but its evolution and modes of spread in Israel are mostly unknown. A possible explanation is that there has been an inter-family exchange of the blaNDM gene between Acinetobacter baumannii and Enterobacteriaceae. However, inter-family horizontal gene transfer (HGT)has never been traced epidemiologically, nor has it been reported in other antimicrobial resistance (AMR) genes. Objectives: 1) To study the transmission dynamics of the blaNDM gene within each bacterial family, Enterobacteriaceae and A. baumannii, using a combined epidemiological-molecular approach; 2) to study the possibility that A. baumannii serves as a source for transmission of the blaNDM gene to Enterobacteriaceae by HGT; 3) to develop a network analysis of transmission of the blaNDM gene. Methods: This will be an observational, multicenter, molecular-microbiological study performed in three consecutive stages: A) identification of patients and collection of isolates; B) molecular analysis of isolates and a descriptive epidemiological study; C) network analysis of transmission of the blaNDM gene. The first stage of the study will be conducted over 18 months in three tertiary-care centers in the three major cities in Israel: a) Tel-Aviv Sourasky Medical Center (TASMC); b) Rambam Medical Center (RMC); 3) Sha'are Zedek Medical Center (SZMC). Clinical and surveillance cultures will be collected according to the routine infection control and clinical practices at each center and will be analyzed for the presence of NDM-producing enterobacteriaceae (NDME) and A. baumannii (NDMAb). All NDME and NDMAb isolates will be studied by whole genome sequencing (WGS) and the data will be used to define the clonal structure and the blaNDM-related mobile genetic elements (MGE). Transmission events (TE) of NDME/NDMAb will be defined according to combined epidemiological and molecular criteria: 1) Epidemiological: a) the suspected NDME/NDMAb infected patients; and 2) a functional in-vitro study of the conjugation efficiency of the blaNDM-harboring plasmids in and between bacterial species and families. Novelty and importance of the study: The novelty of the proposed study is that, in addition to comparing clonal spread and HGT-mediated transfer of a carbapenemase gene within one bacterial family, we will analyze the transmission within and between two phylogenetic bacterial families. We will incorporate a multi-layer approach of studying AMR transmission: molecular-epidemiological investigation, in vitro study of mechanisms of transmission, characterization of clinical features, and network analysis. Our findings will contribute basic science and will guide interventions to prevent the spread of AMR pathogens. The blaNDM is an ideal AMR gene candidate for this study for the following reasons: 1) it has similar prevalence in the two bacterial populations; 2) it has a distinct resistance phenotype that is easy to identify; 3) it has significant clinical and epidemiological importance.

Contact: Grundmann H, Reuter S

Projectstart: 2018

Projectend: 31.12.2021


Medical Director:

Prof. Dr. med. Philipp Henneke
philipp.henneke@uniklinik-freiburg.de


Breisacher Straße 115 B
79106 Freiburg