Transmission Dynamics in Antimicrobial Resistance

Partnership against Biofilm-associated Expression, Acquisition and Transmission of AMR. International Joint Program Initiative in AMR.
The research objectives of this consortium are to i) determine how P. aeruginosa adapts during biofilm formation on surfaces coated with antimicrobials, ii) how AMR mutations are acquired and evolve within mature biofilms, iii) how population dynamics within biofilms affect the transmission of AMR, and iv) translate these findings into clinical practice. To achieve this we will first screen for combinations of antibiotics and antimicrobials that select for/against antibiotic resistance using in vitro models that mimic clinical situations and enable prediction of in vivo antibacterial biomaterial performance, including flow and blood serum components. Surfaces tested will include glass, and other more relevant biomaterials such as polymethylmethacrylate, stainless steel, polyethylene, and polyurethane. Antimicrobials that represent different modes of inhibition/killing and chemical classes will be tested using microtiter and agar plate models to facilitate large scale screening of antibiotic-antimicrobial combinations, and knock-out libraries to identify AMR-related genes. Effective combinations will be chosen for in-depth investigations on their effect on transcriptional and evolutionary adaptations, biophysical properties during adhesion and of mature biofilms, and also the population dynamics of resistant and susceptible genotypes using Macro- and micro-flow chambers. Based on the screening outcome, and the obtained mechanistic understanding, we will then study clinical specimens isolated from patients. As clinical examples we will focus on central venous catheters which are impregnated with chlorhexidine and silver sulphadiazine and are treated with multiple antibiotics when infected, or alternatively endotracheal tubes that are coated with sulfadiazine. These findings will aim to provide clinical recommendations for improved administration of antibiotics/antimicrobials in combination with medical device materials to mitigate against biofilm-associated AMR.