The project has been conducted in three clinical evaluations. These have been performed with world-leading expertise in AMR at five major European hospitals in Sweden, Spain, Italy, Denmark and the Netherlands. Work has focused on four of the most important pathogens that cause sepsis and where the need for improved diagnostics is imminent; Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Acinetobacter baumannii.
Clinical study 1 was aimed to validate the accuracy of the calScreener antimicrobial susceptibility results for single antibiotics to be in concordance with the international ISO-standard (Broth microdilution; BMD) and to establish the time to the diagnostic result. This was successfully completed with high concordance with BMD and significantly faster time to answer at around 6h, enabling same day actionable results. A total of 159 isolates with known antimicrobial susceptibility was tested against 10 of the commonly used antibiotics.
Clinical Study 2 focused on combination testing and synergy identification of antibiotics against multiresistant bacteria, as well as with single agents. To evaluate and validate the in-vitro results of antibiotic combination treatments, results were compared to a sepsis animal model in which the identified synergistic/additive combinations were tested. 158 isolates were tested for single antibiotics and 107 isolates for combination therapy. The results were very encouraging, confirming the ability of the calScreener to predict within hours additive or synergistic antibiotic effects for the treatment of multiresistant infections and therefore be used as a viable tool for screening for new treatment regimens.
Clinical Study 3 included results of antibiotic combination experiments performed on a large multicentric collection of 578 MDR clinical isolates. These were tested with 290 meropenem-colistin and 288 meropenem-amikacin combinations. Overall, a relatively low percentage of isolates (8.6%) showed synergistic/additive effects with meropenem-colistin combination, while a better result was obtained with the meropenem-amikacin combination (22.5%). These results confirmed that synergy in-vitro between meropenem and colistin or amikacin was relatively rare in a large multicentric collection of MDR isolates, which suggests that synergy cannot be assumed without testing. The study also shows that antibiotic combination testing with the calScreener are highly related to checkerboard assays. Together with previous data from study 2, this underlines the importance of accurate rapid synergy testing before treatment. This shows that the calScreener can be a useful clinical tool that is easy to use and less labour intense than checkerboard. Importantly the calScreener can predict the efficacy of different combination therapies within 6 hours, while the checkerboard assay is a minimum of 18 hours.
