Research Herman Goossens

Abstract

The emergence of new pathogens, such as the coronavirus causing the COVID-19 pandemic, and of antibiotic resistance has further increased mortality and morbidity of infectious diseases (ID). To reduce the impact of ID on individual and population health and to advance clinical research on ID, the European Clinical Research Alliance on Infectious Diseases (ECRAID; www.ecraid.eu) was established, a European research infrastructure. The pandemic demonstrated the importance of innovative research into the best management of COVID-19 patients in primary care, where most patients with ID are treated, ideally preventing hospital admission and worse. This is research where both Belgium and Europe lagged behind, and where Flanders could be a pioneer by supporting (B)ECRAID. BECRAID aims to establish a long-term, financially self-sustainable, research infrastructure for primary care research on ID in Flanders and to represent Flanders in the primary care research of ECRAID. BECRAID receives very strong support from its stakeholders and potential users in Flanders and beyond, and has the ambition to expand to nursing homes, to Belgium and even to other relevant diseases.

Researcher(s)

• Promoter: Coenen Samuel
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The COVID-19 pandemic has confirmed and further highlighted the importance of planning and investing in research and innovation well before a health crisis occurs. For this purpose, the main goal of BE READY is to build a consolidated European Research and Innovation Area that provides the foundation of the candidate European partnership for pandemic preparedness so to improve the EU's preparedness to predict and respond to emerging health threats by better coordinating funding for research and innovation at EU, national (and regional) level towards common objectives and an agreed Strategic Research and Innovation Agenda. The Partnership is expected to build on existing pandemic preparedness networks, and work in synergy with the Health Emergency Response Authority (HERA), in close collaboration with ECDC, EMA and other relevant international and European actors. BE READY is composed by 24 organisations from 15 countries with complementary expertise and policy area ranging from Public Health Organisations, Ministries (of Science, University, Health, Innovation or Environment) and Research Performing Organisations that ensures a cross-cutting, interdisciplinary Global Health and One Health approach.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

European citizens affected by COVID-19 have been well-served by landmark clinical trials in hospitals that have found treatments that save many lives. However, there are fewer opportunities for people in the community to contribute to the urgent mission of finding treatments that speed recovery, and reduce the need for hospital admission in the first place. Desperately needed, evidence-based therapeutics for use in primary care have the potential for considerable reach and impact on individual suffering and functioning, as well as on the sustainability of health services. ECRAID-PRIME, a European Adaptive Platform Trial (APT) of COVID-19 therapeutics in primary care will build on many years of EU investment in infrastructure for primary care trials and a mature primary care research network that has pioneered novel, efficient, platform clinical trial designs. ECRAID-PRIME, with a focus on early phase studies of safety and efficacy of exciting candidate treatments for COVID-19 will be rapidly set up. Its goal is to test at least four strong candidate treatments, identifying suitability for inclusion in the next phases of research, and so leading to critical additions to the primary care therapeutic armamentarium against COVID-19. ECRAID-PRIME's primary care focus will help complete the vison for a lasting, integrated, comprehensive and sustainable European clinical research preparedness and response capacity, ECRAID, that will provide a full, integrated suite of international priority clinical trials in intensive care units, hospital wards, and now in primary care.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Variants of concern (VoC) of SARS-CoV-2 raise the possibility of increases in transmissibility, severity and immune evasion. Children and pregnant women who have not been prioritised in the pandemic, are likely to be the last population for whom vaccines are approved and may have low uptake, increasing the risk of VoC arising in this population. Monitoring this group across regions is crucial given rapid changes in epidemiology due to interventions, vaccine rollout and viral evolution. VERDI (SARS-CoV-2 variants Evaluation in pRegnancy and paeDIatrics cohorts) will build on a long-standing infectious disease research and trial network (Penta) to address research questions on the impact of VoC in these vulnerable groups. VERDI's objectives are: i) track and characterise VoC in paediatric and pregnant populations across the globe; ii) understand effects of VoC on clinical outcomes (short/longer term), vaccine effectiveness and transmission characteristics; iii) model outcomes and impacts of VoC; iv) develop evidence-based recommendations for control of COVID-19. VERDI will achieve these objectives by bringing together a diverse range of cohort studies including large scale national and regional level population-based cohort studies from the EU and beyond, providing a unique opportunity for harmonised analysis of data on VoC from a range of sources (e.g. electronic health records, bespoke cohort studies, household transmission studies, screening programmes). We will facilitate expansion of existing studies, e.g. replicating ongoing European household studies elsewhere. Through this approach, VERDI will expand and enhance existing cohort networks, including promoting flexibility to adapt to future emerging infections. The project will improve understanding of the epidemiology and impact of VoC, leading to robust recommendations for control in a range of global settings as well as developing preparedness for future health emergencies.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Around 10% of newborns in Europe will be admitted to a neonatal intensive care unit (NICU). Critically ill babies are a highly vulnerable population for the acquisition of resistant bacteria. Sepsis is among the most common events in NICU and is known to be associated with high mortality and poor long-term outcomes. Despite rising awareness of high rates of resistant bacterial colonisation reported in NICU, there is very little robust specific data on globally applicable infection prevention and control (IPC) measures. NeoIPC focuses on new approaches to the prevention and management of resistant bacterial colonization and infection on NICU. The project builds on and further extends the collaboration between 13 partners with a proven track record in relevant areas, including neonatal infection, IPC, implementation science, microbiology and surveillance. NeoIPC aims to develop and implement an innovative approach towards the evaluation of IPC interventions combining a robust cost-efficient randomised trial combined with the evaluation of a suitable implementation science strategy and novel targeted clinical and genotypic surveillance. A further goal is to generate widely relevant pan-European network strategies to improve IPC in routine neonatal care. This will be achieved through six interrelated work packages to deliver a cluster randomised trialimplementation hybrid investigating the impact of skin antisepsis on infant hospital-acquired clinical sepsis and resistant bacterial colonisation, coupled with a comprehensive implementation strategy incorporating optimal targeted surveillance in a clinical network with tailored dissemination and exploitation to facilitate sustainable embedding of outputs. NeoIPC will generate globally transferrable outputs to reduce hospital transmission of resistant pathogens, foster and facilitate collaborative research and IPC implementation efforts with a broad and long-lasting impact for critically ill newborns and infants.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Co-promoter: Hens Niel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

ECRAID-Base (European Clinical Research Alliance for Infectious Diseases) continues the activities of PREPARE, COMBACTE and ECRAID-Plan, which will lead to establishing ECRAID as an independent non-for-profit legal entity in December 2020. ECRAID-Base is the initial set of activities for ECRAID. As a European clinical research network ECRAID-Base will generate rigorous evidence to improve diagnosis, prevention and treatment of infections and to better respond to EID threats.. The network has already been successfully used during the COVID-19 pandemic, with valuable lessons learned. At the heart of ECRAID-Base are 6 perpetual studies; 5 observational studies in ICU (WP2), ER (WP3,4&5) and primary care (WP6), addressing infections relevant for AMR (VAP in WP2 & cUTI in WP3) and EID (ARI in WP4 & WP6, and Disease X in WP5). All will mature towards adaptive platform trials, with capability to rapidly respond to public health threats. These 5 studies will enroll around 20,000 patients per year. The sixth perpetual study is the Randomized Embedded Multifactorial Adaptive Platform (REMAP) for patients with severe CAP in ICU, with capability of rapid adaptation to new public health threats as demonstrated. In a response to COVID-19 the platform was (within 2 months) adapted with new COVID-19 treatment domains and enrolment of non-ICU patients, and the number active sites rapidly increased in 213 sites (June 4th) with 1084 patients enrolled (567 with COVID-19). Supportive to the clinical studies are work packages LAB (for laboratory support), DATA (for datamanagement and innovative epidemiological and statistical research), TRAIN (for training) and PREP (for improving responsiveness to new public health threats). ECRAID-Base, therefore, establishes a pan-European clinical research network to increase efficiency for testing and developing new diagnostic, preventive and/or therapeutic strategies and therapies and improving responsiveness to new public health threat.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The ongoing COVID-19 pandemic creates an unprecedented burden worldwide. Vaccine-induced immunity is the only promising solution. There is continued need for phase 2 & 3 vaccine trials to reach long-term, large-scale immunity of the entire European population. VACCELERATE will be the pan-European backbone accelerating phase 2 & 3 COVID-19 vaccine trials. The overall objective of VACCELERATE is to connect all European stakeholders involved in vaccine development to provide a pan-European platform for clinical trial design and conduct. VACCELERATE constitutes the rapid response single entry-point to stakeholders from public health authorities to vaccine developers, to address respective needs and kickstart specifically phase 2 & 3 vaccine trials. VACCELERATE conducts capacity mapping of clinical trial and laboratory sites to identify suitable sites for individual phase 2 & 3 vaccine trials. Capacity building via training will increase quality in sites across Europe. Volunteer registries facilitate patient recruitment. Access to laboratory sites and a standardised set of assays essential for clinical phase 2 & 3 trials is provided. A harmonised European approach to vaccine trials is enabled by aligning educational standards, coordination of laboratory support and providing standardised assays and trial protocols. Harmonised data collection, open data sharing and pooling of data for stronger analysis enables data standardisation. VACCELERATE offers solutions for characteristic vaccine development issues during pandemics by closing gaps in public health knowledge and improving knowledge transfer. VACCELERATE amalgamates the vast but scattered expertise across Europe into one network to deliver strategic scientific leadership and guidance on vaccine trials in Europe. Beyond the COVID-19 pandemic, it will be an established pandemic preparedness network, ready to face emerging future pandemics, as well as a pivot in Europe?s capacity to develop vaccines.

Researcher(s)

• Promoter: Goossens Herman
• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Goals of PediCAP are Fill the knowledge gaps on antibiotic therapy of community-acquired pneumonia in pediatric age, in terms of optimal duration, oral step-down schedule evaluating effectiveness, safety and selection of antimicrobial resistance. Evaluate economic impact of antibiotic therapy in terms of cost-effectiveness. Implement the infrastructure that links study sites in order to share knowledge, develop study specific and general research skill straining programme and promote capacity development initiatives.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Antimicrobial resistance (AMR) is of great public health concern, causing numerous losses of lives worldwide and threatening to reverse many of the considerable strides modern medicine has made over the last century. There is a need to stratify antibiotic and alternative treatments in terms of the actual benefit for the patient, improving patient outcome and limit the impact on AMR. High quality, effective and appropriate diagnostic tests to steer appropriate use of antibiotics are available. However, implementation of these tests into daily healthcare practice is hampered due to lack of insight in the medical, technological and health economical value and limited knowledge about psychosocial, ethical, regulatory and organisational barriers to their implementation into clinical practice. VALUE-Dx will define and understand these value indicators and barriers to adoption of diagnostics of Community-Acquired Acute Respiratory Tract Infections (CA-ARTI) in order to develop and improve health economic models to generate insight in the whole value of diagnostics and develop policy and regulatory recommendations. In addition, efficient clinical algorithms and user requirement specifications of tests will be developed fuelling the medical and technological value of CA-ARTI diagnostics. The value of diagnostics will be tested and demonstrated in a unique pan-European clinical and laboratory research infrastructure allowing for innovative adaptive trial designs to evaluate novel CA-ARTI diagnostics. Close and continuous interaction with the VALUE-Dx multi-stakeholder platform provides for optimal alignment of VALUE-Dx activities with stakeholder opinions, expert knowledge and interests. A variety of dissemination and advocacy measures will promote wide-spread adoption of clinical and cost-effective innovative diagnostics to achieve more personalized, evidence-based antibiotic prescription in order to transform clinical practice, improve patient outcomes and combat AMR.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Antimicrobial resistance (AMR) is on the rise, resulting in 700 000 deaths worldwide every year. In Croatia and Hungary, AMR is responsible for the rapid increase in morbidity and mortality rates. The EU-funded AmReSu project will strengthen the innovation capacity in AMR surveillance in both countries, focussing on whole genome sequencing in correlation with next-generation sequencing techniques. It will also establish an "AMR surveillance vision." The project relies on the cooperation of Semmelweis University in Budapest and Klinika za infektivne bolesti "Dr. Fran Mihaljevic" in Zagreb with two internationally leading research institutions, the Laboratory of Medical Microbiology at the University of Antwerp and the Health Research Institute of the Balearic Islands. AmReSu will facilitate knowledge transfer, exchanges of best practices via training activities and the promotion of research excellence.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

this training and education project did not go ahead due to covid. With the agreement of the partners, the project was not taken up even after covid. this training and education project was not taken up by covid. The project was not taken up with the agreement of the partners even after covid.this training and education project was not taken up by covid. The project was not taken up with agreement from the partners also after covid. this training and education project was not taken up by covid. The project was not taken up with agreement from the partners even after covid.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Primary health care providers (PHCPs) like general practitioners (GPs) and their co-workers manage the vast majority of COVID-19 and other patients and keep off the pressure from hospitals. Safeguarding PHCPs' capacity during outbreaks is vital, but currently evidence is lacking on 1. how many PHCPs get infected/diseased in our country, 2. the rate at which this happens, 3. their clinical spectrum, 4. their risk factors and 5. the effectiveness of the measures to prevent this from happening. These questions need answers soon to inform policy makers. We also need more accurate (sensitive!) tests of the immune response. For this, we will evaluate a novel microfluidic dried blood spot (DBS) sampling method and digital ELISA. DBS by fingerpricking is a promising, minimally invasive and transmission safe option for blood (self-)sampling, and already applicable in a multitude of areas. In a subgroup of participants, we will compare test accuracy using the easy-to-use novel DBS method, which further minimises the potential risks of contamination and more precisely meters the required blood volume, to standard DBS.

Researcher(s)

• Promoter: Coenen Samuel
• Co-promoter: Goossens Herman
• Co-promoter: Van Damme Pierre

Research team(s)

• Primary and interdisciplinary care Antwerp (ELIZA)

Project type(s)

• Research Project

Abstract

The true seroprevalence of SARS-CoV-2 in the Belgian population is not known, yet increasing confidence about the performance of several serological assays paves the way to large-scale serosurveys. These studies will be crucial in assessing population immunity and evaluating the risk for re-infection. A major limitation is that antibody (Ab) capture assays measure exposure to SARS-CoV-2, rather than subsequent protection, which requires assessment of the quality of the Abs including their capacity to neutralize the virus. Also the Ab levels required for protection and their longevity are yet unknown. The proposed project aims to address whether neutralizing Ab (nAb) levels correlate with protection in a population of health care workers at risk for re-infection during a second epidemic wave by (1) determining the ex vivo neutralizing capacity and the longevity of SARS-CoV-2-specific Ab responses using a new Ab-capture test and whole virus neutralisation assays, and by (2) measuring the memory B-cell responses.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Van Damme Pierre

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

RECoVER (Rapid European SARS-CoV-2 Emergency Research response) is a comprehensive research response to the SARS-CoV-2 outbreak addressing the most urgent questions for patient and public health level interventions. RECoVER originates from partners of the EU Framework 7 (FP7) funded PREPARE project (Platform for European Preparedness Against (Re-) emerging Epidemics. In RECoVER, we will address these urgent questions in a comprehensive, multidisciplinary and interacting set of research response activities, combing (i) clinical studies in primary and hospital care, (ii) epidemiological studies and modelling, and (iii) clinical biological studies. The proposed studies complement ongoing research in China, addressing key knowledge gaps and patient-cohort questions relevant to the European population. The research proposed includes essential needs for preparedness and response, even if circulation of the virus in Europe will be limited. RECoVER will inform future research response efforts to further strengthen Europe's and global clinical research preparedness to future emerging infectious diseases.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Pneumonia is one of the most common causes of hospital-acquired infections with mortality rates reaching higher than 30%. One in 3 patients receiving mechanical ventilation develop ventilator-associated pneumonia (VAP). Despite this high incidence and mortality, the disease pathogenesis of VAP remains poorly understood. Pseudomonas aeruginosa and Staphylococcus aureus are the most common causes of VAP, and when present together, cause mortality rates of up to 50%. Recent work in our laboratory has revealed an immunosuppressive role of mechanical ventilation that likely plays a role in VAP pathogenesis. Inspired by these data – as well as a growing body of evidence that polymicrobial flora is an important cause of immunosuppression in sepsis and some other infection-related conditions, and that VAP is polymicrobial even though one or two organisms predominate – we intend to test the hypothesis that polymicrobial flora in lungs could also cause local immunosuppression and that, together with MV-induced immunosuppression, leads to growth of pathogenic bacteria in the causation of VAP. Besides this, we also intend to dissect any immunosuppressive role of Staphylococcus spp. in VAP pathogenesis as these organisms are known to have an immune-modulatory role and are frequently (co)-cultured from VAP patients. Lastly, we intend to pinpoint key interactions between P. aeruginosa and S. aureus in a humanized immune context, that together with other objectives could reveal important, and perhaps targetable steps in the pathogenesis of VAP.

Researcher(s)

• Promoter: Kumar-Singh Samir
• Co-promoter: Goossens Herman
• Fellow: Jairam Ravi Kumar

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

Early availability of information on bacterial pathogens and their antimicrobial susceptibility is of key importance for the management of infectious disease patients. MIC-STRIP is a novel phenotypic approach that achieves readout of the antibiotic susceptibility profile of a bacterial infection within 4 hours, moving the time to modify antibiotic treatment from the next day to within the same day.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Verwulgen Stijn

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

ECRAID will develop a business plan in line with European-funded networks to create a clinical research infrastructure that will operate from 2021. This business plan is called ECRAID-Plan. It is working with the network partners and Monitor Deloitte to develop a business plan. The business plan will outline ECRAID services, operations, governance structure, and financial sustainability plans. ECRAID is seeking to strengthen alliances with the private sector and international organisations involved in infectious disease interventions to boost investments into protecting European public health.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The unquestionably needed reform of health and care systems in Europe requires the adoption of innovation and integrated solutions. One way forward is to rethink procurement policies. A positive transformation in this area would be to elevate procurement practices towards an approach that awards the value offered by innovation or integrated solution. The value will be awarded by multi-disciplinary teams responding to specific patients, health care actors and system needs, while taking societal and economic perspectives into account. The EU Coordination and Support Action (CSA) under Horizon 2020 'Innovation in Healthcare' is a highly welcomed initiative. This EU initiative aims at the adoption of innovation in health and care systems and advancing procurement of innovation practices.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Moons Pieter

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

While the threat of antimicrobial resistance is growing, so are the challenges to bringing forward new therapeutic options for patients infected with resistant organisms. There is a need for a better understanding of how antimicrobial resistance is evolving globally, of what novel molecular mechanisms can be exploited as new forms of antimicrobial therapy and of how to more efficiently develop new treatments so they can be more rapidly brought to patients in need. The over-arching concept of New Drugs for Bad Bugs (ND4BB) is to create an innovative public-private collaborative partnership that will positively impact all aspects of ARB through the discovery and development of novel agents for the treatment, prevention and management of patients with bacterial infections. COMBACTE is one of the first projects to be launched under this programme with the aim of developing a broad European network of fully capable and Good Clinical Practice (GCP) compliant clinical investigation sites to execute clinical trials enabling the registration of novel agents to be used in the treatment of patients with bacterial infections.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Clostridium difficile infection (CDI) is one of the most prevalent healthcare associated infections, affecting both hospitalized patients and individuals in the community; notably, there is an increasing realization that cases also occur in subjects not recently exposed to healthcare interventions, including antibiotics. CDI poses an extensive burden of morbidity, mortality and healthcare resource utilization, and so requires effective prevention and management strategies. Epidemiological data are, however, limited and studies typically have examined only part of a healthcare economy and usually have been focused on single countries/healthcare systems. Thus, there is a lack of robust, comprehensive data on the impact of CDI across countries in Europe. Furthermore, we know that large variations in the frequency of testing and the sensitivity of CDI diagnostics across European countries mean that the size of the problem is underestimated. Combating Bacterial Resistance in Europe-CDI (COMBACTE-CDI) therefore aims to develop a detailed understanding of the epidemiology and clinical impact of CDI across multiple European countries. Our project proposal provides a collaborative approach comprising three scientific work packages (WPs). A large epidemiology study will be undertaken across Europe in WP1 to quantify the burden of CDI (incidence, distribution, recurrence, morbidity, mortality, transmission) across the whole healthcare economy. This will be followed by a case/control study in WP2, which along with data collected in a questionnaire will enable the consortium to assess current practices in Europe (guidelines, testing, surveillance, treatment, cost) and their potential impacts. WP3 will create a rich, European, research platform that will provide support for future proof-of-concept and clinical studies of new prevention and treatment strategies for CDI. The three interrelated research WPs will be supported by a management work package (WP4).

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Since two decades, methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of medical device-associated and postsurgical wound infections in hospitals and of pneumonia in the community. In these infections, MRSA favors the biofilm phenotype, living in a community encased in an extracellular matrix that affords protection against the host immune system and antibiotics, making these infections recalcitrant to treatment. Our laboratory has shown that two highly pathogenic and globally successful MRSA clones, USA300 and EMRSA-15, are prolific biofilm formers. Interestingly, our transcriptomics data has revealed spectacularly different mechanisms of biofilm formation between these two clones. For instance, in USA300-S391 biofilms, Hfq, a global regulator of small non-coding RNAs which in turn control rapid bacterial virulence gene expression as well as mecR, which regulates the expression of ß-lactam resistance conferring mecA gene, were both found to be highly upexpressed. EMRSA-15 biofilms, however, were not found to be MecR- or Hfq-dependent, but instead showed upexpression of multiple prophages. This fundamental project aims to dissect the role of mecR, Hfq, and prophages in mediating biofilm formation in USA300 and EMRSA-15. Identifying genes regulated by these key determinants could be better alternatives for biofilm disruption or additive therapies to antibiotics that are currently ineffective against MRSA.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Fellow: De Backer Sarah

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

NeoAMR is a research and development programme run by the Global Antibiotic R&D Partnership (GARDP), a joint initiative of DNDi and the WHO, which aims to develop and deliver new treatments for bacterial infections where drug resistance is present or emerging, or for which inadequate treatment exists. The overarching goal of NeoAMR is to develop new improved treatment regimens for the management of neonatal sepsis in settings with high prevalence of multidrug-resistant and extensively drug-resistant pathogens. Penta is a partner in this project, leveraging its network and experience as a part of NeoAMR research activities.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Human respiratory syncytial virus (RSV) causes severe disease in the very young, elderly and in high risk groups. We have estimated that RSV was associated with 34 million cases of acute lower respiratory tract infection (ALRI), 3.4 million ALRI hospitalisations and 55,000 to 199,000 deaths in children <5 years in 2005 [1]. These estimates were based on limited data and there is a substantial gap in knowledge (on morbidity and associated healthcare and social costs) across Europe. RSV infection in childhood is associated with subsequent wheezing and asthma [2-4]. These long-term sequelae pose a substantial additional burden on the healthcare system. In addition, RSV is a significant cause of ALRI morbidity in elderly and COPD patients [5, 6]. Most published data on RSV disease burden in the elderly (aged >65 years) are from the United States and from hospital settings. The knowledge gaps have an impact on Europe's ability to make evidence-based decisions nationally regarding novel vaccines and therapeutics. There is a parallel need to assemble clinical resources to identify the correlates of severe RSV disease for clinical management, classification of disease severity in clinical trials and identification of biomarkers for severe disease.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Revets Hilde

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Respiratory syncytial virus (RSV) is not well known outside medical circles, yet most people have probably suffered from it in childhood, as it is the most common cause of severe respiratory illness in infants and children worldwide. The elderly and people with weakened immune systems are also vulnerable to RSV infection. While most people's symptoms are mild, it can result in pneumonia and 3.4 million cases annually require hospitalisation. There is no specific treatment or vaccine for RSV. The goal of the RESCEU project is to gather information on the scale of RSV infection in Europe and its economic impacts. It will then use this information to design best practice guidelines to improve the way RSV cases are monitored in Europe, and to shape future vaccination programmes. The team will also gather and analyse patient samples to identify biological markers associated with severe RSV infection. This information could aid in diagnosis and facilitate the development of new treatments and vaccines.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The i-4-1-Health project is aimed at the prevention of infectious diseases and the combat against antibiotic resistance in both humans and animals (One Health) in the border region Flanders-Netherlands. Bacteria are showing an increased resistance against antibiotics. This makes the efficient treatment of infectious diseases more difficult leading to illness, mortality and increased health care costs. The underlying reasons include all parts of the society, like health care, population, agriculture, and the environment. Collaboration with the different disciplines and sectors in the border region is needed to prevent the spread of pathogens. The 26 partners will in a similar way provide insight into the risks of infection, antibiotic use and DNA of resistant bacteria with help of apps and a platform for advances molecular biology analyses. These innovative tools help to map the antimicrobial resistance in the stock farming, the human population and the public health sector. In this way the routes of infection diseases can be traced prematurely and related risks for the society can be minimized. Main objective of this project is the installment of a sustained collaboration that can be further extended in the future.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Given the increasing numbers of bacteria showing resistance against an increasing number of antibiotics, physicians have an urgent need for accurate and clinically actionable data with regard to the antibiotic susceptibility patterns of pathogens. Joint research between the Lab of Medical Microbiology and product development group at the University of Antwerp and the Brussels Photonics team at the Vrije Universiteit Brussel will lead to the development of a microfluidic strip and associated device for the rapid and accurate determination of the minimum inhibitory concentrations (MIC) of antibiotics.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Revets Hilde
• Co-promoter: Vaes Kristof

Research team(s)

Project type(s)

• Research Project

Abstract

Infectious diseases are a major burden to public health and the global economy, not in the least due to antimicrobial resistance. Rapid point of care (POC) in vitro diagnostics (IVD) are key tools in the effective clinical management of patients with infectious diseases. Yet there is still a large unmet clinical need for more rapid POC IVDs generating more clinically relevant, actionable information. Effectively addressing this need requires a change in the current approach in training researchers on IVDs, generating a new 'breed' of IVD researchers capable of closing the gap between the clinical and technological perspective. ND4ID takes up this challenge by offering 15 ESRs a world-class first of its kind training programme where they will be exposed to the full breadth of disciplines spanning clinical, technological and market-oriented viewpoints, from both the academic and non-academic sector. Through a set of synergistic research projects on novel POC assays, targeting the most important and urgent clinical needs at world leading academic or private sector research groups, the ESRs are offered a holistic training program, preparing them to be lead players in the future IVD field. This training through research is augmented by a unique comprehensive network-wide training programme covering clinical, technical and translational knowledge and skills of relevance to IVD research, development and exploitation. As such, ND4ID will deliver ESRs that will be in high demand serving as an example for other academic and non-academic actors active in training IVD researchers and further strengthening Europe's position in the internally competitive arena of IVD technology.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Moons Pieter

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Since two decades, methicillin-resistant Staphylococcus aureus (MRSA) are major causes of medical device-associated and postsurgical wound infections in hospitals and of pneumonia in the community. Recent research shows that in these infections, MRSA favour the biofilm phenotype, living in a community encased in an extracellular matrix that affords protection against the host immune system and antibiotics, making these infections recalcitrant to treatment. Recent data from our laboratory shows that the two most highly pathogenic and globally successful MRSA clones, USA300 and EMRSA-15, are also prolific biofilm formers. Interestingly, transcriptomics has revealed spectacularly different mechanisms of biofilm formation between the two clones. This fundamental project thus aims to dissect the role of novel regulators in mediating biofilm formation in USA300 and EMRSA-15. Identifying genes regulated by these key determinants would initialize identification of targets for biofilm disruption that might be better alternatives to antibiotics that are currently ineffective against MRSA.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Global (mis)use of antibiotics has led to an alarming emergence and spread of antibiotic resistant bacteria (ARB). Countries like Vietnam with unrestricted, over-the-counter antibiotic use are especially prone to the emergence of pan-resistant 'superbugs' and alarmingly, very few treatment options for life-threatening infections. A burgeoning population and inadequate sanitation facilities have likely exacerbated the ARB reservoir in the Vietnamese environment. This study, carried out in Hanoi city and its surroundings, aims to obtain a longitudinal and holistic view of ARB in the community and hospital environments to identify the ARB selection hotspots in Vietnam. To achieve this, we will determine and finely dissect the ARB burden in various ecosystems (water, food, soil) and in the human gut, and link to the burden of ARB in nosocomial and community-related infections. Also, fitness costs of resistance and the impact of residual antibiotics in the maintenance of ARB in reservoirs and in patients will be elucidated. We will utilize state-of-the-art techniques to characterize ARB and beyond state-of-the-art functional metagenomics to elucidate the resistant metamobilome existing in Vietnamese ecosystems. This transnational study between IEHSD, Vietnam and UA, Belgium will not only facilitate extensive exchange of knowledge and expertise between partners but the results generated here will help to target intervention strategies to tackle this public health crisis.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

Since two decades, methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of medical device-associated and postsurgical wound infections in hospitals and of pneumonia in the community. In these infections, MRSA favors the biofilm phenotype, living in a community encased in an extracellular matrix that affords protection against the host immune system and antibiotics, making these infections recalcitrant to treatment. Our laboratory has shown that two highly pathogenic and globally successful MRSA clones, USA300 and EMRSA-15, are prolific biofilm formers. Interestingly, our transcriptomics data has revealed spectacularly different mechanisms of biofilm formation between these two clones. For instance, in USA300-S391 biofilms, Hfq, a global regulator of small non-coding RNAs which in turn control rapid bacterial virulence gene expression as well as mecR, which regulates the expression of ß-lactam resistance conferring mecA gene, were both found to be highly upexpressed. EMRSA-15 biofilms, however, were not found to be MecR- or Hfq-dependent, but instead showed upexpression of multiple prophages. This fundamental project aims to dissect the role of mecR, Hfq, and prophages in mediating biofilm formation in USA300 and EMRSA-15. Identifying genes regulated by these key determinants could be better alternatives for biofilm disruption or additive therapies to antibiotics that are currently ineffective against MRSA.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Fellow: De Backer Sarah

Research team(s)

Project type(s)

• Research Project

Abstract

COMBACTE‐CARE (aligned with the COMBACTE infrastructure) will (1) increase the efficiency of antibiotic R&D through analysing observational clinical and microbiological data sets and making recommendations for the development of novel antibiotic agents for MDR GNB; will (2) provide new knowledge on the clinical management and outcomes of patients (neonates/children and adults) with serious hospitalised infections and will validate this knowledge for clinical outcomes for patients in areas of emerging and endemic antibiotic resistance; will (3) support the sustainability of New Drugs for Bad Bugs (ND4BB) supported investigator and laboratory networks (COMBACTE); will (4) conduct prospective clinical trials with novel trial designs to deliver safety, pharmacology, and proof of efficacy data for novel agents directed towards treatment of infections due to priority MDR pathogens; will (5) validate novel bacterial identification and follow‐up diagnostics or clinical endpoints with the aim of reducing the size and cost of clinical trials; and will (6) provide new knowledge on biomarkers predicting poor outcome in patients with serious healthcare‐associated infections.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand EU. UA provides EU research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The current VAXINFECTIO research is the result of the complimentary work in the multidisciplinary fields of microbiology, vaccinology, and immunology. In the past 6 years, the Methusalem grant has significantly contributed to the development and international recognition in those major fields. The future Methusalem research is aimed at further development of the integrated vaccine and microbiological research, with a special focus on increasing the understanding of the immune response in prophylactic and therapeutic vaccines (including tumor vaccines) and the containment of antibiotic resistance

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Integrated vaccine and microbiological research with a focus on increasing the understanding of the immune response in prophylactic and therapeutic vaccines (including tumour vaccines) and on the containment of antibiotic resistance. Several innovative research topics are ongoing or in the pipeline: potential development of theranostic devices (e.g. rapid Point of Care Diagnostics, optical biosensors, lab-on-chip, microarrays) for pathogen detection and associated resistance in collaboration with several European research partners; potential development of new rapid diagnostic tests and injection devices; potential development of patient-specific cellular vaccines for targeted antiviral and anticancer therapy.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Berneman Zwi
• Co-promoter: Goossens Herman
• Co-promoter: Verwulgen Stijn
• Fellow: Bamberger Martina
• Fellow: Revets Hilde

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

COMPARE aims to harness the rapid advances in molecular technology to improve identification and mitigation of emerging infectious diseases and foodborne outbreaks. To this purpose COMPARE will establish a "One serves all" analytical framework and data exchange platform that will allow real time analysis and interpretation of sequencebased pathogen data in combination with associated data (e.g. clinical, epidemiological data) in an integrated inter-sectorial, interdisciplinary, international, "one health" approach.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand EU. UA provides EU research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The PREPARE project will transform Europe's response to future severe epidemics or pandemics by providing infrastructure, co-ordination and integration of existing clinical research networks, both in community and hospital settings. It represents a new model of collaboration and will provide a one-stop shop for policy makers, public health agencies, regulators and funders of research into pathogens with epidemic potential.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

This project addresses the alarming rise of multiple resistant organisms in an holistic approach by analysing simultaneously different reservoirs of antibiotic resistant bacteria (ARB). These findings will be correlated to the presence of ARB in humans (healthy & patients).

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Cardiff University. UA provides Cardiff University research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Coenen Samuel
• Co-promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other BAPCOC. UA provides BAPCOC research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

Project type(s)

• Research Project

Abstract

While the threat of antimicrobial resistance is growing, so are the challenges to bringing forward new therapeutic options for patients infected with resistant organisms. There is a need for a better understanding of how antimicrobial resistance is evolving globally, of what novel molecular mechanisms can be exploited as new forms of antimicrobial therapy and of how to more efficiently develop new treatments so they can be more rapidly brought to patients in need. The over-arching concept of New Drugs for Bad Bugs (ND4BB) is to create an innovative public-private collaborative partnership that will positively impact all aspects of ARB through the discovery and development of novel agents for the treatment, prevention and management of patients with bacterial infections. COMBACTE is one of the first projects to be launched under this programme with the aim of developing a broad European network of fully capable and Good Clinical Practice (GCP) compliant clinical investigation sites to execute clinical trials enabling the registration of novel agents to be used in the treatment of patients with bacterial infections.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Increase research capacity in the public health sector in Kosovo in order te determine the prevalence of antibiotic resistant bacteria and to improve the quality of antibiotic prescribing in Kosovo, with the overall aim to improve the health and wellbeing of patients infected with antimicrobial resistant (AMR) organisms and their families in Kosovo.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Incidence of infections caused by multi- and pan-drug resistant Enterobacteriaceae, such as Escherichia coli and Klebsiella, is increasing worldwide. Consequently, colistin, an old and out-of-use antibiotic, had to be re-introduced into clinical practice as a last resort therapeutic option as it is the only antibiotic to which such bacteria still remain susceptible. However, increasing use has inevitably led to emergence of colistin resistance (CR) among Gram-negative bacteria. The main goal of this project is to examine key elements of colistin resistant Enterobacteriaceae (CRE) that have hitherto not been fully investigated. We have established a unique collection of CR E. coli and Klebsiella spp., originating from hospitalized patients and sick animals as well as generated in vivo in a Galleria mellonella moth model, that will form the basis of this project. With these isolates and their colistin sensitive counterparts, we plan to undertake the following: 1, Strain typing; 2, Selection of CR in-vitro; 3, Genome sequencing and comparative genome analysis; 4, Targeted gene sequencing and protein expression; 5, Stability studies; 6, Fitness studies and 7, Assessment of mortality and pathogenicity. While strain typing has been done on few Klebsiella, we will type other CRE to examine if CR is associated with certain strain types. Continuous culture experiments in a morbidostat set-up will allow in vitro selection of CRE under continuous drug pressure that will be studied temporally at various stages of resistance development. Whole genome sequencing of in-vivo and in-vitro CRE isogenic strains will identify the sites of mutations potentially responsible for CR. Gene targets identified by genome analysis will be re-sequenced to confirm the changes conferring CR and those will be further characterized by real-time PCR and proteomics. The stability of CR and fitness of such strains will be assessed either by passaging in colistin-free medium, or under constant colistin pressure on the morbidostat model. The effects of CR on mortality will be investigated in the high-throughput reproducible in vivo Galleria mellonella model. Finally, the impact of CR on virulence and pathogenicity will be studied in a higher animal model i.e., a ventilator-associated pneumonia rat model that is already established in our laboratory.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Co-promoter: Sabirova Julia
• Fellow: Xavier Basil Britto

Research team(s)

Project type(s)

• Research Project

Abstract

Biofilm-related infections prove exceedingly difficult to treat because the organisms in a biofilm are protected from the circulating antimicrobials. Up till now, there have been relatively few studies investigating biofilm development in clinical isolates. Current in vitro methods for studying microbial adhesion and growth on biomaterial surfaces lack the influence of the host immune system, endorsing the specific need for animal models that allow temporal and spatial measurements based on non-invasive bio-imaging techniques using reporter strains. To improve our ability to prevent and/or treat biofilms, we need a better understanding of their formation and persistence. The specific goals of this research proposal are to i) understand the physiology of mono- and polymicrobial biofilms, with focus on staphylococci and Candida spp., isolated from indwelling devices from ICU patients and ii) implement in vitro and in vivo laboratory biofilm models that adequately reflect the real-life situation.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Goossens Herman
• Co-promoter: Maes Louis
• Co-promoter: Malhotra Surbhi
• Fellow: Kerstens Monique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Assist 12 non-EU countries with data collection, analysis and rporting of standardized data on the usage of antimicrobial agents for humans at regional/national levels; provide verification and validation of submitted data.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

In ROUTINE, 3 SMEs and 2 Universities will develop a prototype benchtop instrument that will rapidly (< 30 min) detect bacteria and characterize key antibiotics resistance profiles of ESBL (extended spectrum betalactamase) and carbapenemase producing GNB directly from the patient urine at the point of care in outpatients and hospitals at a low cost (~20 €/test) and with near 100% sensitivity and specificity.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Fond. Penta-Onlus. UA provides Fond. Penta-Onlus research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of this project is to develop a next generation sequencing (NGS) platform to advance in a collaborative way biological and medical research within the Antwerp research community. The consortium involves more than 16 research groups in various disciplines of medicine, biology and biomedical informatics. The goals are to identify new genes and mutations in various rare Mendelian disorders, to achieve more insights in the genetic causes of cancer and to unravel more precisely the genetic determinants of infectious diseases. This new knowledge will improve both the diagnosis and management of these human diseases. The project will also focus on the interaction between environment and genes. More specifically, the effect of environmental stressors on genetic variation in aquatic organisms, the effect of teratogenic factors on embryonic development in vertebrates and the effects of environmental conditions on growth in maize and Arabidopsis lines will be studied. The analysis of the large amount of genomic and transcriptomic data, generated by the various research groups, will be coordinated by the recently founded UZA/UA bioinformatics group Biomina

Researcher(s)

• Promoter: Mortier Geert
• Co-promoter: Beemster Gerrit
• Co-promoter: Blust Ronny
• Co-promoter: Goossens Herman
• Co-promoter: Knapen Dries
• Co-promoter: Laukens Kris
• Co-promoter: Peeters Marc
• Co-promoter: Van Hul Wim
• Co-promoter: Vrints Christiaan

Research team(s)

Project type(s)

• Research Project

Abstract

Our study proposes to firstly identify early predictors of pneumonia and secondly, utilize both human samples and rodent models to investigate distinct host-pathogen signatures during colonization and development of VAP by two marker organisms, Pseudomonas aeruginosa and Escherichia coli that not only show diverse pathogenetic profiles but are also most important for VAP etiology.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

The general objective of this project is to co-ordinate, through a durable global network, centres of excellence devoted to community-acquired infections, with the overall aim of reducing antibiotic resistance. Our main goal will be the direct application and integration of the human resources within the proposed network to attain this general objective.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

R-GNOSIS (2011-2015) combines 5 international clinical intervention studies, all supported by highly innovative microbiology and mathematical modelling, to determine - in the most relevant patient populations - the efficacy and effectiveness of cutting-edge interventions to reduce acquisition, carriage, infection and spread of Multi-Drug Resistant Gram-negative Bacteria (MDR-GNB). All clinical work-packages (WPs) will progress science beyond the state-of-the-art in generating new and translational clinically relevant knowledge, through hypothesis-driven studies with a focus on patient-centred outcomes that matter to the people of Europe and beyond. The studies and analyses proposed in R-GNOSIS will generate a step-change in identifying evidence-based preventive measures and clinical guidance for primary care and hospital-based physicians, as well as health-care authorities, to combat the spread and impact of the unprecedented rise of infections caused by MDR-GNB in Europe. The University of Antwerp (UA) is leading the work package on 'Functional microbiology and within-host transmission dynamics of genes, plasmids and clones of MDR-GNB'. Here, we will apply a "bedside-to-bench" translational approach to study the impact of antibiotics and gut decolonization on MDR-GNB pathogens and commensals in the community or hospital utilizing state-of-the-art microbiological tools. Our sophisticated in vitro analyses to investigate resistance gene transfer and the ecology and evolution of resistance will also facilitate ground-breaking modelling studies. Results from the diagnostic interventions planned here will revolutionize current screening practices for MDR-GNBs in hospitals and introduce the use of point-of-care testes (POCTs) in primary care.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand ESF. UA provides ESF research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

Project type(s)

• Research Project

Abstract

RAPP-ID is a five-year European cooperation between 10 academic and 9 industrial partners (4 SME's and 5 major pharmaceutical companies) funded by the European committee through IMI-JU financing. The goal of the project is to develop a test platform that allows the rapid diagnosis of the presence of bacterial, viral or fungal infections. In addition, information about antibiotic resistance will be provided in case of a bacterial infection. In contrast to the current diagnostic tests, which require up to a few days, a rapid diagnostic test (less than 2 hours in the hospital setting and half an hour in primary care) will lead to a more direct treatment and more correct use of antibiotics. Within RAPP-ID, state of the art biotechnological and biochemical techniques will be combined with ultrasensitive detection technologies. RAPP-ID focusses on bloodstream infections, lower respiratory tract infections and tuberculosis.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

Bacterial isolates from intensive care unit patients will be collected from urinary and intravascular catheters and endotracheal tubes. The biofilm phenotype in relation to antibiotic treatment failure will be investigated using molecular biological, bio-imaging techniques and in vitro and in vivo biofilm models. Particular emphasis will be given to Escherichia coli for urinary tract infections (UTI), Pseudomonas aeruginosa for ventilation associated pneumonia (VAP) and Staphylococcus aureus for systemic infections related to venous catheters. The acquired library of fully typed strains will enable in depth study of putative virulence factors that contribute to biofilm formation and treatment failure.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Dewilde Sylvia
• Co-promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The present study aims to combine culture-independent high-resolution sequencing techniques with functional screens to fully characterize the human naso-oro-pharyngeal microbiome and study variations in the antibiotic resistance reservoir in geographically diverse European populations.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

The main aim of this study is to provide a comprehensive picture of the level of clinical relevant antibiotic resistant bacteria (ARB) in the environment and commensal flora in Gauteng/South Africa. Besides, the genetic relatedness of these ARB will be studied to understand the mechanisms of antibiotic resistance dissemination in the community.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Colebunders Robert
• Co-promoter: Malhotra Surbhi
• Fellow: Paasch Fabienne

Research team(s)

Project type(s)

• Research Project

Abstract

Biofilm-related infections prove exceedingly difficult to treat because the organisms in a biofilm are protected from the circulating antimicrobials. Up till now, there have been relatively few studies investigating biofilm development in clinical isolates. Current in vitro methods for studying microbial adhesion and growth on biomaterial surfaces lack the influence of the host immune system, endorsing the specific need for animal models that allow temporal and spatial measurements based on non-invasive bio-imaging techniques using reporter strains. To improve our ability to prevent and/or treat biofilms, we need a better understanding of their formation and persistence. The specific goals of this research proposal are to i) understand the physiology of mono- and polymicrobial biofilms, with focus on staphylococci and Candida spp., isolated from indwelling devices from ICU patients and ii) implement in vitro and in vivo laboratory biofilm models that adequately reflect the real-life situation.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Goossens Herman
• Co-promoter: Maes Louis
• Co-promoter: Malhotra Surbhi
• Fellow: Kerstens Monique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The general objective of the project is to improve the quality of antibiotic prescribing for children in Europe and to reduce the prevalence of antimicrobial resistance in bacterial infections in children.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The general aim of the project is to pilot the EU HAI-AB survey developed by ECDC and which result in a full survey in 2011 in Europe. The survey will be piloted in a large number of European countries. The main objective of this project will be to get an overview of the feasibility of such survey including the identification of the major methodological problems and pitfalls, to test the data entry tools and protocol versions. Additionally, the pilot survey will give the countries the possibility to test different configurations in terms of type of participating hospitals, choice of tools and protocol version prior to the real survey.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Colebunders Robert
• Co-promoter: de Deckere Eric
• Co-promoter: Goossens Herman
• Co-promoter: Meulemans Herman
• Co-promoter: Van geertruyden Jean-Pierre
• Co-promoter: van Sprundel Marc

Research team(s)

Project type(s)

• Research Project

Abstract

SATURN (Impact of Specific Antibiotic Therapies on the prevalence of hUman host ResistaNt bacteria; 2010-2014) is a collaborative research project that is funded as part of the 7th framework programme by the EU. SATURN aims to improve methodological standards and conduct research that will help to better understand the impact of antibiotic use on acquisition, selection and transmission of antimicrobial resistance (AMR) in different environments, by combining analyses of molecular, individual patient-level as well as ecologic data. The anticipated results may guide clinical and policy decisions to ultimately reduce the burden of AMR in Europe. Several clinical trials conducted both in hospitals and in the community will serve as a platform for basic microbiological and pharmacological research carried out by several academic institutions throughout Europe. The University of Antwerp (UA) is coordinating the work package on bacterial genetics and functional studies. The main objective of this WP is to study the abilities of various antibiotics to select for resistance in the respiratory and intestinal flora of patients and their contacts or in nonantibiotic-treated controls and compare the persistence of the selected resistant bacteria over time following antibiotic administration. The functional and genetic studies planned here will utilize both in vitro and in vivo models to dissect the human microbiome. Further studies on the population biology, clonal fitness, and virulence potential of antibiotic-resistant and antibiotic-sensitive bacteria will uncover the mechanisms underlying the successful dissemination of major AMR clones in Europe.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

A first objective of the project is the identification of genes encoding novel virulence factors, which are expressed at the bacterial surface of MRSA. A second objective is to study the differences in biofilm-forming capabilities between hospital-acquired (HA) and community-acquired (CA)-MRSA in the presence and absence of antibiotic pressure. A third objective of this project is to find an explanation why certain MRSA clones are highly epidemic.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand BAPCOC. UA provides BAPCOC research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Integrated vaccine and microbiological research with a focus on increasing the understanding of the immune response in prophylactic and therapeutic vaccines (including tumour vaccines) and on the containment of antibiotic resistance. Several innovative research topics are ongoing or in the pipeline: potential development of theranostic devices (e.g. rapid Point of Care Diagnostics, optical biosensors, lab-on-chip, microarrays) for pathogen detection and associated resistance in collaboration with several European research partners; potential development of new rapid diagnostic tests and injection devices; potential development of patient-specific cellular vaccines for targeted antiviral and anticancer therapy.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Berneman Zwi
• Co-promoter: Goossens Herman
• Fellow: Janssens Anke
• Fellow: Vankerckhoven Vanessa

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

The APRES project aims at providing information and recommendations on the appropriateness of prescribing antibiotics in primary care throughout Europe by collecting information on the antibiotic resistance pattern of bacteria circulating in the community and by combining this information with antibiotic prescribing patterns retrieve from primary care practices. The appropriateness of prescribing antibiotics is defined as the extent to which the pattern of prescribed antibiotics are congruent with the antibiotic resistance pattern of bacteria.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

Project type(s)

• Research Project

Abstract

InTopSens aims to design fast photonic label-free smart biosensors with detection limits below 1 pg/mm2, and integrate multiple biosensors on a disposable label-free photonic biochip capable of identifying and determining antibiotic resistance of bacteria causing sepsis. Severe sepsis or septic shock is characterized by multi-organ dysfunction, failure and finally death. In the EU, sepsis is estimated to cause a loss of up to 146,000 lives every year and up to EUR 7.6 billion in patient health care costs. The most important intervention is rapid diagnosis followed by appropriate antibiotic treatment. However, the currently available 'rapid' assays are laboratory based with a total assay time of up to 12 hours, e.g. PCR. Hence, more often than not, antibiotic treatment has to be instituted empirically before test results arrive and this non-targeted, and quite often inappropriate, antibiotic use has led to multidrug resistance amongst bacteria including those causing sepsis. We intend to develop the InTopSens device into a modular assay for sepsis to detect the causative pathogen and also profile its antibiotic resistance at the patient's bed-side in Emergency/Intensive Care Units in hospitals. Upon introduction of a large drop of blood (~ 50 µl) onto the chip, presence of bacteria and identification to the genus/species level will be obtained within 5-10 mins, while the antibiotic resistance profile of the bacterial pathogen will be available within 30 mins. Some 120 sensing areas/datapoints are needed to identify this profile and as such due to the very high integration up to 5 assays can be integrated onto a 1cm2 chip of the same bacteria for higher sensitivity and selectivity or for other bacteria. A final prototype consisting of a packaged biochip will be validated both preclinically and clinically to assess the potential of this sepsis assay in preventing/reducing inappropriate antibiotic therapy and mortality in sepsis patients.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

TheraEDGE (An integrated platform enabling Theranostic applications at the Point of Primary Care), is an Integrated Project supported for four years by the European Commission as part of FP7, ICT ¿ Information and Communication Technologies, Objective ICT-2007.5.1 (Personal Health Systems for Monitoring and Point of Care Diagnostics). The main objective of this project is the rapid detection of organisms that cause CA-LRTI (Community acquired lower respiratory tract infections) and the identification of resistance profiles to antibiotics that are commonly used for the treatment of these infections. A viable diagnostic system based on single molecule detection will be developed for the early diagnosis and treatment of LRTI at the point of primary care. The Laboratory of Medical Microbiology (UA) is leading two workpackages in TheraEDGE, Clinical definition/validation and Bioassay development. The Clinical definition/validation platform aims at the validation of the TheraEDGE device by assessing its analytical specificity, sensitivity and reproducibility and by testing its performance on clinical specimens in comparison with the best available conventional methods. A selection of the most relevant etiological agents of CA-LRTI and associated antibiotic resistances will be made during the Bioassay development. Moreover, probes will be developed against multiple targets for highly specific detection of pathogens causing CA-LRTI and finally the probe design will be validated for the lab-on-a-chip format.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

The prevention and treatment of bacterial and viral infections are the main focus of the Methusalem project VAXINFECTIO. Antibiotic resistance, anti-tumoral and antiviral cellular immune responses by dendritic cells, the evaluation of vaccination, and the socio-economic aspects of the use of vaccines and antibiotics are research topics that will be addressed. The Vaccine & Infectious Disease Instituut (VAXINFECTIO) of the Universiteit Antwerpen - consisting of the Laboratory of Medical Microbiology (LMM), the Laboratory of Experimental Hematology (LEH) and the Centre for the Evaluation of Vaccination (CEV) - maintains a close collaboration with the Centre for Statistics (CenStat) of the Universiteit Hasselt.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Berneman Zwi
• Co-promoter: Van Damme Pierre

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

General objectives: To participate with a Flemisch primary care Network in GRACE. Specific objectives: 1. To determine the proportion of bacterial LRTI. 2. To describe the most important bacterial species in LRTI and to determine to what extent they are resistant to antibiotics. 3. To validate the CRB-65 prediction rule to assess the risk on complications in general practice. 4. To review national and international guidelines on lower respiratory tract infections. 5. To assess whether an evidence-based intervention package reduces antibiotic prescribing for community-acquired LRTI.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel
• Co-promoter: Van Royen Paul

Research team(s)

Project type(s)

• Research Project

Abstract

The research plan over the next years involves four main research themes: 1.1.Modelling infectious diseases; 1.2.Data collection and analysis for burden of (infectious) disease estimates; 1.3.Program evaluations of infectious disease interventions; 1.4.Health economics and program evaluations in general. Each of these research themes departs from the observation that the current methodological approach can be substantially improved by using more sophisticated methods. Since these research themes are each multidisciplinary and interconnected, these improvements are expected to occur within each theme and over all themes combined.

Researcher(s)

• Promoter: Goossens Herman
• Promoter: Van Damme Pierre
• Fellow: Beutels Philippe
• Fellow: Coenen Samuel

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the project is to develop a translational platform for integrated vaccine research, building upon the expertise of the Vaccine and Infectious Diseases Institute as regards the set-up and implementation of vaccine trials (phase I-IV), microbiological diagnostics and basic immunological research. This platform will operate according to ISO standards, and thanks to a swift transition from lab to 'bed-side', and to a swift feedback from bed-side to lab, will guarantee a fast development of a new generation of HPV vaccines. This platform will create the opportunity, in collaboration with the industrial partner, to develop serological and urine tests for early efficacy testing and follow-up of vaccinees. In addition, basic research into the mucosal cellular immunity can be initiated within this cooperation structure. The financial input of this project will allow the Institute to consolidate the available knowledge of HPV-testing and to further develop this knowledge with a clear focus on economic valorisation; furthermore, the existing collaboration with the pharmaceutical industry will get an additional dimension with new opportunities of expansion and collaboration.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Berneman Zwi
• Co-promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of this project is 1. Analyse baseline resistance and changes effected by amoxicillin use on the oropharyngeal bacteria of LRTI patients and study the mechanisms of phenotypic tolerance in this patient population. 2. Elucidate telithromycin resistance mechanisms in SPY. 3. Determine the fitness costs and any compensatory mutations in macrolide- (including telithromycin) resistant SPY and amoxicillin-resistant SPN.

Researcher(s)

• Promoter: Goossens Herman
• Fellow: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

The overall aim of the ESAC (European Surveillance of Antimicrobial Consumption) project will be to consolidate the continuous collection of comprehensive antimicrobial consumption data, from ambulatory and hospital care, from the 27 EU Member States, 3 EEA/EFTA and 3 candidate countries (Croatia, Former Yugoslavian Republic of Macedonia and Turkey). Additionally, the project will deepen the knowledge of antibiotic consumption by focusing on specific consumption groups and/or patterns in collaboration with those countries where the appropriate data are available. This will be achieved in 4 different subprojects focusing on ambulatory care, hospital care, nursing homes and socio-economic determinants.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

We will harmonise the registration of antimicrobial use in all Member States of the European Community, in countries signatories to the Agreement on the European Economic Area and in associated countries of Central and Eastern Europe. A data collection system will be developed allowing to produce comprehensive national data on cost and volume of antibiotic consumption, in ambulatory and in hospital care. Standardised national data will be assembled in a European database for sub-regional comparison of antibiotic consumption. Additionally, the database will contain information on determinants of antibiotic use, quality indicators of good antibiotic practice, strategies used in different European Countries to control antibiotic consumption and a reference list of ongoing projects and related articles published at the national and international level. The database will be accessible for scientists and health authorities in order to link antibiotic use to resistance patterns and to assess the impact of intervention strategies at the community and hospital level. The results and recommendations should allow health authorities in the different Member States to promote evidence-based antibiotic use.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

The aim of CHAMP (Changing behaviour of Health care professionals And the general public towards a More Prudent use of anti-microbial agents) is to promote the appropriate use of antibiotics by developing effective tools to change behaviour of health care professionals, patients in primary care, and the general public on the prescription and use of antibiotics. Effective interventions in this field should take into account cultural differences between countries and be based on knowledge of perceptions and behaviour of medical professionals, patients and the general public within the European Union. Therefore the first stage of the project will explore current prevention and management of respiratory tract infections in European primary care and perception, expectations and illness behaviour of primary care patients with respiratory tract infections. Then an up-to-date inventory of both published and unpublished public campaigns and behavioural programs will be made and qualitative information from key-players and stake-holders in this field will be gathered. Cost-effectiveness of the different interventions used until now will be modelled. In addition, information will be gathered systematically on educational programs from medical schools on prevention and management of common respiratory tract infections. The information thus gathered will be analysed and priorities chosen. Consensus will be aimed for among experts and stakeholders on tools to improve the behaviour of medical professionals and the public concerning prevention and management of infectious diseases and antibiotic use. In addition, standard procedures will be developed to measure the effects of educational activities, behavioural programs and public campaigns in this field. Finally, the implementation of the behavioural program that is thus developed will be tried out and evaluated in six GP networks in six different countries. This will be done in close collaboration with the GRACE project.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

Project type(s)

• Research Project

Abstract

MOSAR is an Integrated project supported by the European commission for five years (2007-2012) under the Life Science Health Priority of the Sixth Framework program, with a focus on major multiresistant pathogens present in European hospitals. The overall objective of MOSAR is to gain breakthrough knowledge in the dynamics of transmission of multi-drug antimicrobial resistant bacteria, and address highly controversial issues by testing strategies to combat the emergence and spread of antimicrobial resistance, focusing on major and emerging hospital pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterobacteriaceae producing extended spectrum beta-lactamases (ESBL), and Acinetobacter spp. To achieve this objective, interventional clinical trials have been planned in diverse high-risk health settings (ICUs, Surgery, rehabilitation units) in more than 30 hospitals/rehabilitation centers across at least 15 European member states and Israel. During these clinical trials the impact of rapid detection of MRSA, VRE and ESBL as a strategy to curb antibiotic resistance will be investigated. At the University of Antwerp (UA) extensive validation of commercially available chromogenic media and molecular methods for the detection of MRSA, VRE and ESBL producing strains will be performed to determine the optimal tests for implementation during the clinical trails. Also new, innovative molecular methods will be developed in collaboration with small and medium enterprises. These methods will be validated in a clinical setting during the clinical trials, after pre-clinical optimalization and validation. A collection of strains gathered from the participating hospitals will be established at the UA and information on this collection will be stored in a general database. In collaboration with MOSAR partners these strains will be fully characterized and epidemicity of MRSA and VRE will be determined.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

For many problems encountered in primary care strong evidence to support management is lacking. In addition there is a problem of implementing evidence-based management in everyday practice. Both lead to sub-optimal patient care and misuse of available resources. Respiratory tract infections are a good example of this (Coenen S. Antibiotics for coughing in general practice [Dissertation]. University of Anwerp 2003). For lower respiratory tract infections (LRTIs) the evidence for the effectiveness of antibiotics is conflicting. Furthermore, the evidence does not allow to identify those patients who would (not) benefit from antibiotic treatment. For otitis media with effusion (OME) antibiotics are of very limited benefit. On the other hand the relevant evidence base on the overall effectiveness of surgery is provided in OME. Here however poor selectivity for referrals by GPs to ENT was documented. The current research project aims to inform the development of interventions to improve the predictive validity of OM referrals and to improve pragmatic choices about the use of antibiotics for all patients with LRTI and for important clinical subgroups of patients with LRTI.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Van Royen Paul
• Fellow: Coenen Samuel

Research team(s)

Project type(s)

• Research Project

Abstract

e-Bug is a European wide, DG SANCO funded, antibiotic and hygiene teaching resource for junior and senior school children. This resource will reinforce an awareness of the benefits of antibiotics, but will also teach about prudent use and how inappropriate use can have an adverse effect on an individual's good bugs and antibiotics resistance in the community. The areas of hand and respiratory hygiene and spread of infections in the community will be covered, including teaching how to wash hands most effectively. As the internet has become a powerful vehicle for education, the pack will be accompanied by a website hosting complementary games and interactive quizzes.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

GRACE is a Network of Excellence focusing on the complex and controversial field of community-acquired lower respiratory tract infections (LRTI), which is one of the leading reasons for seeking medical care-The promiscuous use of antibiotics to treatment of LRTI accounts for a major part of the community burden of antibiotic use and contributes dramatically to the rising prevalence of resistance among major human pathogens. The overall objective of GRACE is to combat antimicrobial resistance through integrating centres of research excellence and exploiting genomics in the investigation of community-acquired LRTI. Microbial and human genomics will be integrated with health sciences research consisting of clinical observational and intervention studies, health economics and health education to specifically change practice in managing community-acquired LRTI. GRACE is exceptional as it brings together investigators from basic laboratory sciences, clinical medicine, and health economics. In the jointly executed research programme, 17 academic groups, spread widely across 9 EU Member States and 5 SMEs will participate. GRACE will organise professional education, including web-based teaching and practical courses, through two leading European scientific societies (European Society of Clinical Microbiology and Infectious Diseases and European Respiratory Society) to disseminate the excellence of the programme. A high level of co-ordination will be obtained through a professionally IT-supported and rigorous management structure, so as to achieve optimal synergy of the components of GRACE. We aim to develop a genomic laboratory network in 8 European countries and a primary care research network in 11 European countries during the first 18 months of the project, and then to build on the infrastructure to create the jointly executed research programme. The consortium will become a virtual "European LRTI Research Centre" potentially leading to a forum promoting research and good practice in the field of community-acquired LRTI.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

Objectives: -To study the effect of pre-emptive aciclovir therapy to prevent the invasion of the lower respiratory tract by HSV in patients in intensive care with reactivation of HSV in the oropharynx, in a double blind placebo controled randomized study and to measure differences in outcome between treated and untreated patients. -To further objectivate the incidence rate of HSV reactivation in the respiratory tract of critical care patients and define risk factors for the reactivation of the virus. -To evaluate genome homologies between HSV isolated between and within patients. -To compare the sensitivity of conventional viral culture and molecular detection methods, and to demonstrate any relation between the viral load and disease severity/progression or outcome by using quantitative PCR techniques

Researcher(s)

• Promoter: Ieven Margareta
• Co-promoter: Goossens Herman
• Co-promoter: Jorens Philippe

Research team(s)

Project type(s)

• Research Project

Abstract

We will harmonise the registration of antimicrobial use in all Member States of the European Community, in countries signatories to the Agreement on the European Economic Area and in associated countries of Central and Eastern Europe. A data collection system will be developed allowing to produce comprehensive national data on cost and volume of antibiotic consumption, in ambulatory and in hospital care. Standardised national data will be assembled in a European database for sub-regional comparison of antibiotic consumption. Additionally, the database will contain information on determinants of antibiotic use, quality indicators of good antibiotic practice, strategies used in different European Countries to control antibiotic consumption and a reference list of ongoing projects and related articles published at the national and international level. The database will be accessible for scientists and health authorities in order to link antibiotic use to resistance patterns and to assess the impact of intervention strategies at the community and hospital level. The results and recommendations should allow health authorities in the different Member States to promote evidence-based antibiotic use.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

For many problems encountered in primary care strong evidence to support management is lacking. In addition there is a problem of implementing evidence-based management in everyday practice. Both lead to sub-optimal patient care and misuse of available resources. Respiratory tract infections are a good example of this (Coenen S. Antibiotics for coughing in general practice [Dissertation]. University of Anwerp 2003). For lower respiratory tract infections (LRTIs) the evidence for the effectiveness of antibiotics is conflicting. Furthermore, the evidence does not allow to identify those patients who would (not) benefit from antibiotic treatment. For otitis media with effusion (OME) antibiotics are of very limited benefit. On the other hand the relevant evidence base on the overall effectiveness of surgery is provided in OME. Here however poor selectivity for referrals by GPs to ENT was documented. The current research project aims to inform the development of interventions to improve the predictive validity of OM referrals and to improve pragmatic choices about the use of antibiotics for all patients with LRTI and for important clinical subgroups of patients with LRTI.

Researcher(s)

• Promoter: Van Royen Paul
• Co-promoter: Goossens Herman
• Fellow: Coenen Samuel

Research team(s)

• Primary and interdisciplinary care Antwerp (ELIZA)

Project type(s)

• Research Project

Abstract

Targeted surveillance of antibiotic resistance in the Mediterranean partner countries through the collection of comparable antimicrobial susceptibility results will be undertaken over a period of 48 months. Results will be validated by a quality assurance programme and will be assembled into a antibiotic resistance database. ARMed will also investigate potential factors involved in the epidemiology of antibiotic resistance by collecting data on antibiotic consumption and infection control policy. Methodology for data collection within the ARMed project will be the same as previously developed within the EARSS, ESAC and HARMONY projects, enabling linkage with established European databases.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The increasing incidence of atopic diseases in children is thought to be due to the 'Western way of living'. Decreased microbial exposure at a young age, exposure to environmental chemicals and pollution induce allergic reactions. Recently, the gut flora of healthy infants showed differences with allergic infants. The influence of different aspects of a 'Westernized' lifestyle on the bacterial flora of the gut will be evaluated in infants in relation to the development of atopy and asthma.

Researcher(s)

• Promoter: Desager Kristine
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

In Belgium ESBL-producing E. aerogenes strains have become common. They exhibit epidemic potential, and can transfer their resistance plasmid to other species of Enterobacteriaceae. The use of cefepime as an effective therapy against infections due to ESBL producing E. aerogenes, is highly controversial, mainly because of a paucity of clinical data. The aim of the study is to investigate if there is a correlation between the clinical outcome of patients infected with an ESBL producing E. aerogenes treated with cefemine and the type of ESBL isolated from these patients.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Probiotic bacteria, mainly lactic acid bacteria (LAB) (e.g. lactobacilli, pediococci, enterococci, and bifidobacteria) have been considered safe for human consumption. However, recent reports of clinical infection, the spread of antibiotic resistance genes, and development of new and/or modified probiotic LAB strains, have caused concern of safety. This project aims to assess the biosafety of LAB. Isolates from healthy humans and immunocompromised patients, commercially available and new probiotic LAB will be studied. After polyphasic taxonomic identification, their biosafety will be assessed by: (i) the detection of antibiotic resistance and horizontal transfer of antibiotic resistance genes; (ii) the detection of known and new virulence properties; (iii) evaluation of immunological adverse effects of LAB; (iv) the survival, colonisation, and genetic stability of probiotic LAB in the human gut. The project will result in recommendations for biosafety and biosafety testing of LAB, which will be presented and discussed at a final conference.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

Before 1990, the annual incidence of meningococcal disease in Belgium fluctuated around one case per 100,000 inhabitants. However, since the beginning of the 1990s the incidence of meningococcal disease gradually increased from 0.8 cases per 100,000 inhabitants in 1990 to 3.7 cases per 100,000 inhabitants in 2001. In the early 1990s this increase was mainly due to genotypically related serogroup B isolates, first identified in the Netherlands and designated lineage III strains. Comparison of Dutch and Belgian isolates suggested a southward migration of a genetically well-delineated lineage of strains causing disease in the Netherlands since the early 1980s and in Belgium since the early 1990s. From 1997 a clonal replacement started to take place in Belgium. The number of serogroup B strains gradually decreased, which was associated with an increase in the number of serogroup C strains, more in particular phenotype C:2b:P1.2,5 strains of cluster A4.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Hospitalised patients world-wide are increasingly at risk of acquiring infections caused by antibiotic resistant bacteria which can lead to serious clinical complications. It is widely accepted that this problem has emerged due to selective pressure and poor infection control practice. Across Europe different control measures are in place to varying degrees to try to avert this problem. This project will collate information on such procedures and ultimately recommend optimum measures to reduce the incidence of antibiotic resistance in hospitals. 1) There is a lack of good quality information on the prevalence of antibiotic resistance and amounts of antibiotic used. Methods will be developed and put into practice for collation, classification and quality assessment of existing data in Europe. 2) Antibiotic policies and infection control policies will be scored and audited for their association with low levels of antibiotic resistance rates in transmissible organisms. 3) Rapid identification and typing of micro-organisms is essential in tracking the epidemiology of antibiotic resistant bacterial pathogens at both local and European levels. It is also essential to assess the effectiveness of infection control policies. Data from current typing studies will be collated and 'gold standard' methods for local and reference laboratories recommended. All data collated in this project will be modelled in order to identify antibiotic policies associated with low antibiotic resistance rates and to identify infection control policies associated with low rates of transmissible pathogens.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

During a two year period (November 2001 ' October 2003), actions will be taken to harmonise the registration of antimicrobial use in all Member States of the European Community, in countries signatories to the Agreement on the European Economic Area and in associated countries of Central and Eastern Europe. A data collection system will be developed allowing to produce comprehensive national data on cost and volume of antibiotic consumption, in ambulatory and in hospital care. Standardised national data will be assembled in a European database for sub-regional comparison of antibiotic consumption. Additionally, the database will contain information on determinants of antibiotic use, quality indicators of good antibiotic practice, strategies used in different European Countries to control antibiotic consumption and a reference list of ongoing projects and related articles published at the national and international level. The database will be accessible for scientists and health authorities in order to link antibiotic use to resistance patterns and to assess the impact of intervention strategies at the community and hospital level. The results and recommendations should allow health authorities in the different Member States to promote evidence-based antibiotic use.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

Resistance against macrolides of Streptococcus pyogenes in increasing in Belgium. This resistance is due to either targer modification or efflux. This study aims to investigate the prevalence of macrolide resistance of these respiratory tract pathogens, the mechanisms of resistance by detection of the resistance genes, molecular typing of resistance strains and investigation of the activity of telithromycin against these organisms.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The in vitro activity of cefoxitin and norfloxacin against contemporary bacterial isolates recovered from several hospitals in Belgium will be investigated for re-licensing purposes. In 4 Belgian hospitals around 150 bacterial isolates will be collected between April and June 2001. Of these, 100 should be nonfastidious microorganisms and 50 should be fastidious microorganisms. Subsequently, the antimicrobial susceptibility of these isolates will be determined centrally by the broth microdilution method using rehydrated MIC panels. Fastidious organisms will also be tested by the Etest.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

In this study herpes simplex virus in the upper en lower respiratory tract of intensive care patients will be detected bV conventional and molecular techniques. Genotyping of the isolates will be developed to define their origin and possible pathological role. Investigations will be carried out to identify the immune defence mechanisms that are involved in the pathogenesis of these infections. Ultimately, we aim to conduct prospective randomised studies on the treatment and prevention of these infections.

Researcher(s)

• Promoter: Ieven Margareta
• Co-promoter: Goossens Herman
• Co-promoter: Jorens Philippe

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

This project will result in a number of rapid 'real time' multiplex nucleic acid amplification tests (NAAT) covering the whole spectrum of causes of atypical pneumonia, and in algorithms for their application. Each of the four partners will in close collaboration develop part of the necessary tests, the combination of which will result in NASBA (RNA targeted) and PCR (DNA targeted) multiplex tests. The participation of an industrial company is of crucial importance to solve technical problems. The tests will be cross-validated between the partners by the use of proficiency panels. The tests developed will be clinically validated by application to significant numbers of thoroughly documented respiratory specimens collected by three of the partners. The analysis of the results will allow to decide on algorithms to be used for the etiologic diagnosis of CAP. The aim of this project is the development and standardisation of molecular techniques with real time detection by the use of molecular beacons of the etiologic agents responsible for this syndrome and to optimize the diagnostic usefulness by combining the individual tests in multiplex formats because the traditional approaches for the diagnosis of atypical pneumonia are slow, insensitive and cumbersome. The joint effort of 4 labs, each of them having expertise and competence in different aspects of the problem should guarantee the achievement of the objectives. The implementation of the reactions developed should result in improved health care by both more rapid diagnosis and the correct identification of a greater number of etiologic agents responsible for atypical pneumonia resulting in improved patient care, better justified use of antimicrobials and decreased antibiotic pressure resulting in antibiotic resistance.

Researcher(s)

• Promoter: Ieven Margareta
• Co-promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The objective of the study is to establish an international surveillance program to evaluate and publish the in vitro activity of Linezolid, an oxazolidone, and selected other antimicrobial agents against a representative sample of common aerobic and facultatively anaerobic Gram-positive bacteria isolated from wounds, abdominal acity, respiratory tract and blood cultures.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Aim of the study is to evaluate the NucliSens Basic Kit for the detection of M. pneumoniae, C. pneumoniae and L. pneumophila in order to get an impression of the quality of the Basic Kit reagents, the quality of the information as provided in the package insert and the userfriendliness and performance characteristics of the Basic Kit software. The next research questions will be answered: Can an assay be created according to the package insert, how does the Nuclisens Basic Kit assay compare to a standard home-made NASBA assay and which controls are required apart from the positive control that is supplied with the kit to monitor the isolation, ampification and detection procedure? The following issues will be addressed: Modification of existing NASBA primers and probes to the Basic Kit format, synthesis and purification of Basic Kit based primers and probes, evaluation of the analytical sensitivity of the Basic Kit based primers via testing of dilution panels and comparison to standard NASBA primers, evaluation of Basic Kit based ECL-detection of NASBA amplicons and comparison to standard ECL-detection of these amplicons, evaluation of the Basic Kit positive control in respiratory samples and the analysis of clinical respiratory samples. Furthermore, the userfriendlyness of the software (can assays be defined, edited and deleted?) and the performance of the software (are runs achieved correctly, does the software calculate the results correctly, can runs be retrieved properly, ') will be evaluated.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Resistance of E. coli and Klebsiella against broad-spectrum cephalosporins in increasing due to the production of specific beta-lactamases which are capable of hydrolysing these antibiotics. This project aims to investigate the prevalence of such strains in Belgian hospitals. Methods for detection will be evaluated, the beta-lactamase gene will be characterized, and strains will be typed by means of molecular methods.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Early detection of carriers of those multi-resistant organisms and rationalization of antibiotic use may be important measures to control the emergence and spread of such organisms. The objectives of the study are: prospective epidemiologic study on the incidence of colonization and infection with antibiotic resistant Enterobacteriaceae, including extended spectrum beta-lactamases (ESLB) producing strains, in patients admitted e.g., in the intensive care units (ICU) of the University Hospital Antwerp; study of the phenotypic and genotypic characteristics of the multi-resistant strains, in order to document their mechanisms of resistance and investigate their relatedness and transmission; study of risk factors associated with colonization or infection with multi-resistant gram negatives; prospective study of the relationship between the appearance of antibiotic resistant organisms and antibiotic use at the level of the indivudual patient; if indicated, study of the horizontal transfer mechanisms of antibiotic resistant strains; improve patient care through an adapted antibiotics administration policy.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Resistance against macrolides of Streptococcus pyogenes in increasing in Belgium. This resistance is due to either targer modification or efflux. This study aims to investigate the prevalence of macrolide resistance of these respiratory tract pathogens, the mechanisms of resistance by detection of the resistance genes, molecular typing of resistance strains and investigation of the activity of telithromycin against these organisms.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

CAMPYLOBACTER Campylobacters are the most frequently identified bacterial causes of diarrhea in the United States and Europe. Diarrhea caused by C. jejuni and C. coli is a self-limiting disease and does not require therapy except in severe cases with prolonged disease and serious symptoms. Erythromycin is an old and well-established antimicrobial agent which has been the drug of choice for Campylobacter enteritis. Fluoroquinolones have also proved effective in the treatment and prevention of Campylobacter diarrhea. Several recent reports, however, have described a substantial increase of fluoroquinolone resistance in Campylobacter species. Campylobacter infection is mainly a food-borne disease in which poultry play a particularly important role. There is growing scientific evidence that the use of antibiotics in food animals leads to the development of resistant pathogenic bacteria that can reach humans through the food chain. About 400 Campylobacter strains isolated from healthy broilers, layers, turkeys and pigs will be investigated. First, strains are identified by mutiplex PCR and/or SDS-PAGE of whole-cell proteins. Subsequently their activity to 6 antimicrobial drugs will be determined by the agar dilution method. The antibiotics tested are: erythromycin, ampicillin, nalidixic acid, ciprofloxacin, tetracycline and gentamicin. SALMONELLAE Human nontyphoidal Salmonella infections are the primary cause of foodborne disease in developed countries, resulting in considerable morbidity and occasionally death, especially in immunocompromised patients. Strains of Salmonella that are resistant to antimicrobial agents have become a worldwide health problem. Fluoroquinolones are the drugs of choice for treatment of human invasive salmonellosis. However, strains resistant to these antibiotics have been noted. Therefore, continued concern about the development of antimicrobial resistance in these organisms is warranted. The antimicrobial susceptibility to 11 antibiotics will be investigated for about 400 Salmonella strains isolated from healthy broilers, layers, turkeys and pigs. The antibiotics tested are: ampicillin, ceftriaxone, kanamycin, streptomycin, sulfamethoxazole, trimethoprim, cotrimoxazole, tetracycline, nalidix acid, ciprofloxacin and chloramphenicol.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

A polyphasic-taxonomic study is performed in order to (l) determine the bacterial biodiversity of respiratory tract infections in cystic fibrosis patients; (2) establish the role of the different taxa identified routinely as 'B. cepacia' (classical plant pathogenic isolates strains from soil and water samples, isolates from cystic fibrosis patients, and strains of potential biotechnological interest will be included), and (3) develop an identification procedure that will allow to identify all Burkholderia-like organisms in a rapid and correct way.

Researcher(s)

• Promoter: Goossens Herman
• Fellow: Vandamme Peter

Research team(s)

Project type(s)

• Research Project

Abstract

Antibiotic resistance and in particular glycopeptide resistance, is an ever-increasing problem in enterococci which are currently the fourth-leading cause of nosocomial infections. Molecular analysis of the enterococcal genome enables us to identify a strain at species and strain level (PCR and PFGE), and to study the dissemination of transposons responsible for the antibiotic resistance.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The in vitro activity of cefpirome will be compared to other antibiotics against gram positive blood isolates collected in 25 Belgian hospitals by means of agar dilution and E test.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

We are studying the incidence of group A streptococcal (GAS) infections in Belgium. Isolate and study with regard to the presence of virulence factors (M-proteins, exotoxines). The GAS are typed based on PCR and "pulsed field gel electrophoresis".

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Using molecular methods such as ribotyping, PCR-based methods, and analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis, the genetic variability of several medical important bacterial populations would be investigated, including Neisseria species, enterococci, and Bordetella species. They respectively show an epidemic, a moderate varying and a stable population structure.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The presence of enterococci in the gut will be investigated. Strains will be identified at the species level; they will be tested for their susceptibility to vancomycine and teicoplanin. Patiens colonized with multi-resistant enerococci will be treated with Enterococus faecium SF68.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The late eighties have witnessed the emergence of severe group A streptococcal infections in previous healthy hosts. We will study the incidence of such infections in Belgium. Isolates will be further characterized with respect to the production of toxins, M-type and spread of clonal variants.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The susceptibility of all gram-negative and gram-positive clinical isolates will be determined for 16 antibiotics by means of the Kirby Bauer disk method.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The susceptibility of blood isolates collected from 25 hospitals situated in Belgium and Luxembourg over a period of 6 months will be determined for cefepime and other antibiotics, by means of disk diffusion, open dilution and E test (AB Biodisk).

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Lower respiratory tract infections in the community are an important and frequent medical problem. In only about 50 % ot lower respiratory tract infections is a pathogen identified. We will apply Nucleic acid sequence based amplification" (NASBA) for the detection of virusses from the respiratory tract specimens.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

A significance increase of the number of cases of meningococcal meningintis in the Province of Antwerp occurred in 1993. The possible spread of a more virulent clone will be investigated by means of Pulsed Field Gel Electrophoresis and Random Amplified Polymorphic DNA typing antibiotic resistance will be studied as well.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Pseudomonas aeruginosea, collected at the laboratory for medical microbiology of the University Hospital Antwerpen will be tested against ceftezidime and cefepime by means of van dilution and E test (AB Biodisk, Zweden).

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

This polyphasic taxonomic study of several poorly characterised streptococci will enable to improve species identification. This will allow to evaluate the clinical significance of each to those species. In addition, genomic fingerprinting methods will be developed in order to perform epidemiological studies on these bacteria.

Researcher(s)

• Promoter: Goossens Herman
• Fellow: Vandamme Peter

Research team(s)

Project type(s)

• Research Project

Abstract

Antibiotic resistance is increasing in hospitals. Antibiotic policy should be based on antibiotic resistance patterns. This project aims to study the epidemiology of antibiotic resistance at the University Hospital and the study of the resistance mechanisms.

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

Evidence suggests that life threatning infections due to Str. pyrogenes are increasing in the western hemisphere. This could be related to certain M-types or to the production of some special toxins. This study aims to investigate the epidemiology of Str. pyrogenes, serious infections in Belgium (M-typing, detection of toxins).

Researcher(s)

• Promoter: Goossens Herman

Research team(s)

Project type(s)

• Research Project

Abstract

The absence of rapid and specific typing produces for Helicobacter pylori hampers epidemiological studies. In the present research we evaluate the suitability of research typing techniques using a set of well characterized isolators.

Researcher(s)

• Promoter: Goossens Herman
• Fellow: Vandamme Peter

Research team(s)

Project type(s)

• Research Project