Kombinationer av antibiotika och icke-antibiotika för behandling av multiresistenta bakterier (CO-ACTION)
Tidsperiod: 2015-12-01 till 2018-11-30
Projektledare: Thomas Tängdén
Budget: 5 367 330 SEK
The CO-ACTION project aims to develop and provide a framework for evaluating and validating the effectiveness of antibiotic (AB)- and non-antibiotic (NA) combinations (COMs) in the preclinical setting based on pharmacokinetic/pharmacodynamic (PKPD) principles both for human and veterinary medicine. To fulfill this ambitious goal, 6 work-packages with 6 interacting partners were built involving several steps that are executed partly sequentially, partly in parallel with significant interaction. The interaction between existing ND-AB from at least 6 different classes, including Polymyxin B, will be determined using checkerboard experiments and/or specific techniques for NA for well characterized Gram-negative (e.g. P. aeruginosa, K. pneumoniae) multidrug resistant strains and analysed by interaction modelling. In parallel, an automated system (the oCelloscope) will be applied to allow efficient screening for large numbers of COMs. The CO-ACTION of clearly synergistic COMs will be further quantified using time-kill curves (TKC), subsequent validation using PKPD experiments and modelling and finally testing of the most promising 3-6 COMs in up to 5 available animal models. Finding optimal COMs is ensured by a continuous feedback between experimental results, PKPD modelling and statistical evaluation.