Multi-drug resistant Gram-negative bacteria (MDR-GNB): the ultimate challenge!Antibiotic resistance is a global public health concern recently elevated to the top three threats identified by the WHO, and subject of numerous national and international government activities. Although focused strategies have beneficially influenced infection rates due to methicillin resistant Staphylococcus aureus (MRSA), infections due to MDR-GNB are rapidly increasing. In a very recent report the Centers for Disease Control and Prevention concluded that Carbapenem-Resistant Enterobacteriaceae (CRE) represent an immediate public health threat that requires urgent and aggressive action (CDC: Antibiotic Resistance Threats in the United States 2013).The epidemiology of MDR-GNB, and especially of CRE, is characterized by large heterogeneity in genotypes (with >20 reported resistance genes, such as NDM, KPC, VIM, OXA-48) and even larger heterogeneity of phenotypes, seriously hampering rapid detection of resistant types when using routine susceptibility testing. Treatment of infections caused by CRE relies on combinations of “older” antibiotics, lacking a strong evidence base of effectiveness and safety. New treatments for these infections are, therefore, urgently needed.The COMBACTE-CARE consortium is building on the recently funded Topic 1a/b/c consortium: COMBACTE, and contains three networks: CLIN-Net, LAB-Net and STAT-Net. To fulfil the specific objectives of Topic 5 the consortium has focussed on capacity building in clinical sites in some of the new member states in south-eastern Europe, where infection rates with MDR-GNB are expected to be high. Together with high-quality study sites in countries with endemic levels of MDR-GNB (such as Israel and Greece) CLIN-Net and LAB-Net will maximize capacity to provide a highly efficient resource for the conduct of the proposed studies on ATM-AVI. Furthermore, the consortium brings in four of the most prominent MDR-GNB diagnostic research groups in Europe, able to address the diagnostic challenges for the epidemiological and clinical studies, and a highly successful – and already operational – cohort for biomarker identification in critically ill patients. Furthermore, the participation of the PENTA network offers the unique opportunity to efficiently include neonates and children in the observational studies. The COMBACTE-CARE consortium brings together 20 academic partners (10 also partner in COMBACTE) and two CROs that build upon prior EU Commission investments which present unique expertise and capabilities to the overall project partnership. For all these reasons, APC2 (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 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 MDR pathogens, prevention or sequelae of infections due to priority 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.