Clinical validation of novel methods to diagnose antibiotic interactions and heteroresistance

PI(s)/Head responsible for the resource:

Dan I. Andersson

Host organisation(s):

Uppsala University

Resource description:

Antibiotic resistance is a major pandemic, associated with around 5 million deaths per year. This has increased the demand for better antibiotic susceptibility testing (AST) methods to maintain therapeutical options and prolong the lifespan of existing antibiotics. Current susceptibility tests miss two critical threats: heteroresistance (HR), where rare mutant sub-clones escape therapy, and the drug-interaction landscape that decides whether an antibiotic pair synergizes or not. Our objective is to eliminate both blind spots by clinically validating two ultra- low-cost, plate-based assays that turn bedside isolates into treatment guidance within 16 h.

The project builds on our previous/ongoing VR, KAW and NIH funded basic research where we established proof-of-concept for both methods and also performed laboratory studies of clinical isolates. Based on these results, the main focus now is to validate the methods in clinical settings in both retrospective and prospective studies, which will later allow us to perform treatment studies to directly assess the impact of applying these methods on morbidity and mortality.

Both methods are based on growth of bacteria (in presence of antibiotics) on agar-plates of a certain geometry. After growth, a picture is taken of the agar-plate with a mobile phone and a designed software automatically determines if the antibiotics interact synergistically (wanted) or antagonistically (not wanted). Similarly, for detection of HR the number of colonies is automatically counted in zones with different antibiotic concentrations to determine the fraction of resistant cells. The methods give robust results without use of any special instrument in 16 hours and are easy and cheap to integrate into the work pipeline in any microbiology laboratory and resource-setting.

Contact information:

Dan I. Andersson
Medical Biochemistry and Microbiology, Uppsala University
Email: Dan.andersson@imbim.uu.se