Rapid metagenomic sequencing for diagnosis and antimicrobial sensitivity prediction of canine bacterial infections

Abstract

Antimicrobial resistance is a major threat to human and animal health. There is an urgent need to ensure that antimicrobials are used appropriately to limit the emergence and impact of resistance. In the human and veterinary healthcare setting, traditional culture and antimicrobial sensitivity testing typically requires 48–72 h to identify appropriate antibiotics for treatment. In the meantime, broad-spectrum antimicrobials are often used, which may be ineffective or impact non-target commensal bacteria. Here, we present a rapid, culture-free, diagnostics pipeline, involving metagenomic nanopore sequencing directly from clinical urine and skin samples of dogs. We have planned this pipeline to be versatile and easily implementable in a clinical setting, with the potential for future adaptation to different sample types and animals. Using our approach, we can identify the bacterial pathogen present within 5 h, in some cases detecting species which are difficult to culture. For urine samples, we can predict antibiotic sensitivity with up to 95 % accuracy. Skin swabs usually have lower bacterial abundance and higher host DNA, confounding antibiotic sensitivity prediction; an additional host depletion step will likely be required during the processing of these, and other types of samples with high levels of host cell contamination. In summary, our pipeline represents an important step towards the design of individually tailored veterinary treatment plans on the same day as presentation, facilitating the effective use of antibiotics and promoting better antimicrobial stewardship.