Description of the partners

Participant 1 (Coordinator) – Université de Liège (ULg)

General description

The Centre for Protein Engineering (CIP) is an internationally recognized 30 years old, multidisciplinary research centre. The ambition of the CIP of the University of Liège is to offer an integrated approach to the study of proteins, to the analysis of their functional properties and the determination of their structure. As a basis for this approach, the Centre chose a problem of major scientific and practical interest: the study of the mode of action of β-lactam antibiotics and the resistance mechanisms devised by bacteria to escape the lethal effects of these compounds.

Domains of excellence (expertise) and added value to the project

Internationally recognized expert in protein production and purification, Biochemistry, Enzymology and Bacteriology. Prof. B. Joris, former CIP director and head of Bacterial Physiology and Genetic has a strong experience in protein science and bacteriology (especially in molecular mechanism of antibiotic resistance)

Participant 2 – Université catholique de Louvain (UCL)

A. Pharmacologie cellulaire et moléculaire – Prof. F. Van Bambeke and P.M. Tulkens (http://www.facm.ucl.ac.be)

General description

The research interests of the group (3 permanent researchers, 4 post-doctoral fellows, 11 PhD students and 4.5 technicians) include the study of (a) PK and PD of antibiotics (both in vitro [cellular PK] and in clinical samples), (b) resistance (in particular, low level resistance mechanisms like efflux) in relation with antibiotic use and are thus at the frontier between laboratory and clinical research. P.M. Tulkens/F. Van Bambeke are authors of 198/129 publications [PubMed] (H-factor scopus: 34/29). 

Domains of excellence (expertise) and added value to the project

Internationally recognized experts in antibiotic PK/PD; regularly delivering conferences at national/ international meetings; excellent publication record in PK/PD and resistance by efflux; past/present board members of the PK/PD of Anti-Infectives Study Group of the European Society of Clinical Microbiology and Infectious Diseases, the International Society for anti-infective Pharmacology, and the International Society of Chemotherapy.
Editors of international journals dealing with antibiotics (research and clinical aspects): Antimicrobial Agents and Chemotherapy, International Journal of Antimicrobial Agents, Infection, Antibiotics, Chemotherapy. Submitters of scientific papers to the above journals and to European and American journals in the same discipline (Journal of Antimicrobial Chemotherapy, Clinical Microbiology and Infection, Clinical Infectious Diseases, Journal of Infectious Diseases).
Partner 2 will thus actively contribute to dissemination (WP13). Experience in managing research programs combining laboratory and clinical research helpful for the coherence of the whole program (Liaison officer). Experimental work will contribute to the global quality of the research program.

B. Laboratory of Therapeutic Drug Monitoring (TDM)

General description

Prof. P. Wallemacq is head of the laboratory of Therapeutic Drug Monitoring (TDM) of the Cliniques Universitaires St Luc, UCL, Brussels. Since about 30 years, his major professional expertise has been focused on TDM and clinical pharmacokinetics of immunosuppressive drugs and antibiotics, as reflected by his > 170 peer reviewed manuscripts, > 10 book chapters, and number of PhD students supervision. He works in close relationships with clinicians from different care units (intensive care, pediatric, transplantation …). His team possesses expertise in all fields related to the modern concepts of TDM (analytical methods, pharmacogenetics, pharmacodynamics and pharmacokinetics).

Domains of excellence (expertise) and added value to the project

Prof. P. Wallemacq will provide his practical TDM expertise to the consortium. He will be able to perform the validation/comparison of the MON4STRAT enzymatic assay by a reference HPLC-MS-MS method. Recently elected President of the International Association of therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), he will be able to serve as ideal link between international opinion leaders in the field of TDM and MON4STRAT. He will dedicate one of his Post-doc fellows to the analytical validation and to collaborate with EXPRIMO to the PK-PD modelling.

Participant 3 – WOW Technology

General description

WOW Technology is a 30 years company specialized in mecatronics tailor-made turnkey solutions. Due to the very high part of R&D in its project, WOW’s team is mainly composed of engineers (15 in mechanics and physics, 7 in electricity and electronics, 8 in software development). But WOW’s workshop is also very complete, with its own CNC machine, welding stations, cabling and mounting people. With its network of over 800 suppliers, WOW is present on several high tech sector such as : Airspace industry (for Ariane 5, Vega, Airbus…), Automotive industry (for AGC, VW, Audi, Ford,…) and Pharmaceutical industry (for GSK, Baxter, IBA, …). For this last customer for example, WOW is making the most advanced PID controls of the patient’s positioner (for this Ion Beam Therapy, the beam is fixed and the patient needs to be moved very precisely to be cured at the right place).

Domains of excellence (expertise) and added value to the project

WOW’s “Laboratory and Medical Device” Department has already developed and built several very high precision devices such as holographic microscopes, medical slides laser engraving machine, micro-fluidic fluorescent readers. Those devices are developed using ISO 9001-2008 quality system, or even ISO-13485 for the medical parts. The L&MD Dpt not only develops and builds the prototype, but it also has facilities to build small to medium size series (typically from 20 to 200 pieces/year).

Participant 4 – Institute of Cardiometabolism and Nutrition

General description

The Service de Réanimation Médicale is a medical intensive care unit that consists of 26 beds. It is located inside the “Institut de Cardiologie”, Hôpital Pitié-Salpêtrière, Paris, France and is one of the components of ≤ who require advanced monitoring and care in the ICU setting. Its medical staff consists of 10 fulltime specialists, who have special training in the care of critically ill patients. Special areas of service include: Management of shock and cardiopulmonary resuscitation, Respiratory failure, Multisystem organ failure (including renal and hepatic), Sepsis (infection), Central nervous system crises, Cardiac failure, Transplantation.

Domains of excellence (expertise) and added value to the project

Dr J. Chastre is a Professor of Medicine at Paris 6 University School of Medicine, Faculté de Médecine Pitié-Salpêtrière, in Paris, France. He is also the Director of the Medical Intensive Care Unit and of the Intermediate Care Unit at Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière in Paris, France. Dr. Chastre is a recognized expert in the performance of clinical outcomes research in the ICU setting, and his clinical research focus has been the understanding, diagnosis, and treatment of nosocomial infections and the improved care of mechanically ventilated patients. Dr. Chastre has published over 200 peer-reviewed papers, and authored or co-authored 18 book chapters. As such, he has the expertise and experience for designing and conducting a prospective, randomized, open, controlled, multicenter study to evaluate the safety and efficacy of the MON4STRAT approach for optimizing -lactam therapy in intubated and mechanically-ventilated, adult patients with Gram-negative pneumonia. He will assume the WP7 leadership and contributes to WP9-Emergence of EDR, WP10-Data Mgt and WP11-Statistics, WP12-Proposals for improvement of current treatment algorithms, WP13-Ethics issues and to WP14-Dissemination & Exploitation.

Participant 5 – Servicio Madrileno de la Salud (SERMAS)

General description

The Servicio Madrileño de Salud (SERMAS) is the administrative and management structure that integrates all public health services of the Madrid Region. The Ramón y Cajal University Hospital, within SERMAS, a 1,200 bed University hospital founded in 1977, includes a basic research department with research infrastructures. The Foundation for Biomedical Research (FiBio) concentrates research activities of this Hospital, which ranks among the best of all Spanish hospitals.

The Dept. of Clinical Microbiology, the operational partner in the project, has a high publication rate – a mean of 100 of impact factor/year during the last five years. It is a fully equipped Dept. with clinical diagnostic duties and molecular biology research clinically oriented (16 researchers, including 4 leaders) and has participated in different EU-projects (ref: DEAR-QLK2-CT-2001-873; COBRA-LSHM-CT-2003-503335; EAR-LSHM-CT-2005-518152; DRESP-LSHM-CT-2005-0180705; ACE-LSHM-CT-2007-037410; KBBE-2008-2-4-02-BIOHYPO; TROCAR-HEALTH-F3-2008-223031; PAR-HEALTH-F3-2009-241476; EVOTAR- HEALTH-F3-2011-282004; R-GNOSIS-HEALTH-F3-2011-282512).

Domains of excellence (expertise) and added value to the project

The Dept. of Microbiology will be the WP-leader of WP8 and concentrate their research activities related with WP2, WP3 and WP6 and with transversal activities in WP10 and WP11. It has extensive experience on microbiological studies on multi-resistant Gram-negative bacilli, including detection, characterization of resistance mechanisms, population structure analysis and mobile genetic elements. It has fully-equipped laboratory research facilities able to perform current genetic research in microbiology, including, cloning, sequencing, conventional and real-time PCR, PFGE, MLST and PCR-based typing methods, and bioinformatics equipment. Expertise is relevant in antibiotic resistance, evolutionary and population genetics, biochemistry and ecology of resistance, bacterial virulence, clonal detection, phylogenetic analysis, characterization of integrons, transposons, and plasmids, and in full-sequence genomics of pathogens. It has skills on bioinformatics analysis. This expertise will be added to the project in the understanding of emerging of drug resistance in relation to PK/PD parameters. Members of this Dept. belong to different EU groups related with PK/PD knowledge including EUCAST (European Committee for Antimicrobial Susceptibility Testing). It has participated in clinical trials with both Medical Intensive Care Unit and Infect. Disease Departments.

Participant 6 – University of Houston

General description

The University of Houston is the leading public research university in Houston, Texas, USA. Each year, more than 40,750 students in more than 300 undergraduate and graduate academic programs are educated on campus and online. UH awards more than 7,800 degrees annually, with more than 200,000 alumni. The College of Pharmacy is located in the Texas Medical Center, the largest medical complex in the U.S. and an internationally recognized community of healing, learning and discovery. The Texas Medical Center is home to many of the nation’s best hospitals, physicians, researchers, educational institutions and health care providers. Recognized by U.S. News & World Report’s Annual Survey of American’s Best Hospitals, the 54-member institutions of the Texas Medical Center (total hospital beds: 6,900; Annual International Patient Visits: 16,000) are known throughout the world for the quality of patient care, teaching, research and prevention of illness and injury.

Domains of excellence (expertise) and added value to the project

The University of Houston College of Pharmacy has a strong research program in Infectious Diseases therapeutics. There are currently 7 full-time faculty members sub-specializing in various aspects of the discipline. In particular, the investigator involved in this proposal (Dr V. Tam) is a leading world expert in PK/PD modeling and Gram-negative resistance. Dr Tam has published more than 100 peer-reviewed papers in these areas and his research program has received support from the National Science Foundation and the National Institutes of Health in the U.S. Dr Tam will play a leadership role in WP2, where he would lead proof-of concept (translational) investigations to establish optimized PK-PD that would result in EDR suppression. The established target drug exposures to suppress EDR will be adopted in the dosing algorithm of the subsequent clinical study. Furthermore, Dr. Tam will also participate in establishing a library of beta-lactam PK/PD model profiles (WP2), the development of a decision-making process translating actual blood levels into proposals for dose readjustments (WP5) and validating the simple monitoring methodology in a U.S. hospital (WP6 part 1).

Participant 7 – Université Libre de Bruxelles (ULB)

A. Infectious Desease Department

General description

Erasme University Hospital is the academic hospital of the Université Libre de Bruxelles. The hospital has 829 beds including a 32-bed department of intensive care. This is a multidisciplinary hospital with a large proportion of surgical and immunosuppressed patients (mainly solid organ transplant recipients). The infectious diseases department (ID) includes 5 full-time physicians and 2 data nurses. The major fields of interest are influenced by the patient population in the academic hospital: the management of severe infections in high risk patients, such as intensive care unit patients and immunosuppressed patients.

Domains of excellence (expertise) and added value to the project

Prof. Jacobs is the head of the ID Department at ULB’s academic hospital. She has more than 25 years of experience in conducting clinical trials. The members of the ID department are currently involved in many studies, both from the Industry and in academic studies. Prof. Jacobs has conducted many clinical trials in the domain of optimization of antimicrobial agents. These studies have been possible because a therapeutic drug monitoring team (TDM team) for antimicrobial drugs was created at Erasme hospital, performing TDM for many antimicrobial drugs that are not usually performed in other hospitals (e.g., numerous beta-lactams, antifungal drugs like voriconazole and posaconazole, colistin and caspofungin). Prof. Jacobs has already successfully conducted with 4 other ICUs a multicentre study on optimization of beta-lactams and amikacin in ICU patients and has also extensively collaborated with an Australian team very active in clinical trials on pharmacokinetic/pharmacodynamic relationships of anti-infectious drugs.

B. Intensive Care Department

General description

Erasme University Hospital is the academic hospital of the Université Libre de Bruxelles. It has 829 beds including a 32-bed department of intensive care. This is a multidisciplinary hospital with a large proportion of surgical and immunosuppressed patients (mainly solid organ transplant recipients). The department of intensive care has 12 full-time physicians (7 clinical leaders and 5 residents) and 3 data nurses.

Domains of excellence (expertise) and added value to the project

Prof. J.L. Vincent is Professor of Intensive Care at the ULB and Head of the Department of Intensive Care at Erasme Hospital. He has a large clinical and research experience in the field of intensive care, with a particular interest in sepsis. He has authored or co-authored more than 800 peer-reviewed publications, about 90 books and more than 800 original abstracts, many related to the fields of sepsis and infectious diseases. He has been principal investigator on several international multicenter clinical trials of therapies for sepsis. Prof Vincent is Secretary General of the World Federation of Societies of Intensive and Critical Care Medicine and President of the Belgian Society of Intensive Care. He has received many awards for his work, including the prestigious Belgian scientific award of the FRS-FNRS (Prix Scientifique Joseph Maisin-Sciences biomédicales cliniques).

Participant 8 – UDSL, Université Lille Nord-de-France, CHRULille

General description

Our paediatric University Hospital belongs to one of the main University Hospital in France. It includes 230 beds for neonates and children. There is one neonatal intensive care unit (NICU) with 16 beds and one paediatric intensive care unit (PICU) with 14 beds with medical and surgical patients in both units. Two paediatric infectious diseases (PID) specialists work in close relationship with these units.

Domains of excellence (expertise) and added value to the project

F. Dubos, Associate Prof. in Paediatrics & Infectious Diseases, works with M. Lagrée, MD involved in antibiotic resistance and prescribing in children. This PID team is involved in the EA2694 university research team, entitled: “public health, epidemiology and quality of care”. Our research activity is mainly focused on the evaluation of the weight of various infectious diseases in children and on the way to improve the quality of care. Prof. S. Leteurtre is a staff member of the EA2694 research unit. He is an active member of several French societies. He has conducted several international studies and obtained grants from the French Ministry of Health and collaborated in several studies with European (Dr. Parslow, PICANet group) and Canadians partners (Prof. Lacroix in the PALISI project). Prof. Leteurtre is in charge of the development of the French PICU registry. Prof. L. Storme has a research team on the perinatal environment and particularly on the physiology of lung diseases in neonates. He has local and national responsibilities related to his clinical activity and research.

Participant 9 – University of Tartu

General description

University of Tartu is an academic institution with main focus on under- and postgraduate teaching and research. Tartu University Clinics is a multidisciplinary hospital with 986 beds covering the population of 500,000 and 5,000 annual births. The other institution involved is Tallinn Children’s hospital that for neonatal cases covers an area with the population of 800,000 with 10,000 births per year. Both hospitals are tertiary care referral centres with about 700 babies treated (about 60% mechanically ventilated) in the third level NICU annually.

Domains of excellence (expertise) and added value to the project

At the Institute of Microbiology of the University of Tartu we have formed a research group to evaluate the pathomechanisms and management of infections in neonatal age. The group is very much research oriented and consists of neonatologists, microbiologists, clinical pharmacologist and chemists. The leader of the group is Irja Lutsar who has experience in the pharmacokinetic studies in children and experimental animals as well as in designing and conducting international clinical trials. The main aims of the group are to evaluate antibiotic PK-PD, especially in extremely low birth weight infants. Our most recent studies include evaluation of PK of several β-lactams (penicillin G, meropenem, ampicillin) in extremely low birth weight infants. We are key partners of NeoMero1 trials, a randomised controlled trial to evaluate efficacy and safety of meropenem vs standard of care in late onset neonatal sepsis.

Participant 10 – SGS-Exprimo

General description

SGS Exprimo NV is a consultancy company applying model-based approaches and related services in support of pharmaceutical research and development. Exprimo develops and uses drug-disease modeling and clinical trial simulation (M&S) with focus on optimizing (pre)-clinical development strategies. The staff of Exprimo is composed of 14 scientists specialized in pharmacometrics and working from home offices located in Sweden, The Netherlands, United Kingdom, Belgium, Switzerland and France. Area of services include: population pharmacokinetics, advanced PK/PD modeling and simulation, advanced drug disease modeling and simulation PK-PD study design optimization, pediatrics, pre-clinical PK and PK/PD, regulatory consulting, customized training, data management services in PK-PD.

Domains of excellence (expertise) and added value to the project

Exprimo is a well-recognized organization in Europe specialized in pharmacometrics. Over the last 10 years, Exprimo has participated to more than 200 modeling and simulation projects for pharmaceutical companies in different disease area, including infectious disease. Some of these projects have been applied in registration dossiers for drug approval. Philippe Jacqmin and Eric Snoeck, the two Directors of Exprimo, have extensive experience in drug development within the pharmaceutical industry. Together, they have published more than 40 original research papers and 60 scientific abstracts and contributed to six textbooks dealing with pharmacokinetics and PK/PD modeling.

Exprimo will collaborate in the MON4STRAT consortium by sharing and improving the state-of-the-art methodologies in modeling and simulation applied to therapeutic drug monitoring (TDM) and individualized therapy.

Participant 11 – AEPODIA

General description

Aepodia is specialized in early drug and medical device development (including proof of concept trials) and provides scientific consultancy as well as operational support in various indications including but not limited to CNS, Endocrinology, Metabolic Diseases, Infectious Disease and Oncology.

Domains of excellence (expertise) and added value to the project

Aepodia designs clinical development plans, study protocols and implements, manages and performs clinical trials, by offering “ad hoc” or “full service” support to complement the sponsor’s internal teams (e.g., regulatory strategy, study design, project coordination, monitoring, competent authority submission, site selection/assessment/management, data management, medical writing…).

General description of the organisation

Assistance Publique – Hôpitaux de Paris (AP-HP) is the public hospital system of the city of Paris and its suburbs. It provides healthcare, teaching, research, prevention, education and emergency medical service in 52 branches of medicine; it employs more than 92 000 people (practitioners and administrative staff) in 44 hospitals. AP-HP is linked with the University of Paris and its seven colleges of medicine, two of odontology and two of pharmacy. It is the largest hospital system in Europe and the most important group of hospitals in France, including numerous expert centers with international reputations.

Currently managing more than 100 European projects, AP-HP has developed a vast experience in the management of European projects funded under FP7, including European studies where AP-HP is the sponsor (promoter) of clinical trials.

Since 2009, 2 departments (International promotion and European affairs) work in close collaboration with investigators, researchers and clinical research units to ensure the follow up of clinical trials promoted by AP-HP when involved as coordinator or as partner in FP7 funded projects.

Domains of excellence (expertise) and added value to the project

ICAN is an university-hospital center.  Professors Chastre and Luyt  work as volunteers for ICAN. Their work is carried out within the framework of their activity  for APHP.