Easy-to-use diagnostic tool for the killing efficacy of antibiotics on clinical isolates

ended

This proposal aims to develop a low-cost diagnostic tool (SurviDisk) that can evaluate the killing efficacy of antibiotic treatments on bacterial strains isolated from patients. Current methods, such as the disk diffusion assay, only evaluate the ability of antibiotics to arrest the growth of bacteria. The size of the inhibition zone in the disk diffusion assay indicates the Minimum Inhibitory Concentration (MIC) i.e. the resistance level of the strain, but cannot distinguish between a cidal drug from an antibiotic that only stops the growth of bacteria without killing. It is today recognized that antibiotics that are able to kill bacteria are crucial for hard to treat infections that persist for many days despite treatment. However, bacterial strains can evolve to become tolerant and avoid killing by antibiotics. This tolerance is distinct from resistance, and only allows the strains to survive under antibiotic treatments but does not increase their MIC. The enhanced survival of these strains under antibiotics is not detected in the current antibiotic susceptibility tests done in hospitals. In the parent ERC-CoG grant, we have recently shown that measuring the survival of clinical strains isolated from life-threatening bloodstream infections enables to choose better treatments. Based on these results, we propose to develop a single disk easy-to-use low-cost assay for a semi-quantitative measurement of survival of bacteria under antibiotics, the Survidisk. We will develop the Survidisk prototype and evaluate its efficacy at predicting the treatment outcome on a retrospect analysis of a collection of clinical strains. Contacts for the production and commercialization by companies selling disk diffusion assays will be developed. We expect that the routine use of the SurviDisk for guiding antibiotic therapy in persistent infections should greatly treatment outcome, reducing death rates and shortening significantly hospitalization duration.