Next generation sequencing as a panacea for antibiotic susceptibility testing: yea or nay?

Practical next generation sequencing (NGS) technologies are entering the high-throughput diagnostic clinical microbiology laboratory. Bacterial whole genome sequences (WGS) can be used for detection and identification of species and their (relative) quantification. Genomic relatedness and epidemiological spread of strains of microorganisms can be traced, in parallel with detection of virulence genes as well as genes involved in antimicrobial resistance (AMR). The latter potentially facilitates genomic antimicrobial susceptibility testing (gAST). AMR mechanisms and the genes involved are diverse and require dedicated supporting databases in order to be accurately detected by microbial genomics. The present document assesses the current position of NGS and gAST assays in the clinical microbiology laboratory and discusses their role in establishing a clinically actionable antibiogram which defines the spectrum of antibiotics to which a given microbial strain is susceptible or resistant. Key question is whether or not gAST has added value as compared to current AST methodologies. Full diagnostic implementation of gAST in the routine medical microbiology laboratory is as yet impossible. The technical complexity of gAST still needs a significant decrease, gAST data management needs to be improved and simplified, the timeliness of the gAST assays requires improvement, and costs need to go down. The throughput of genomic testing for large-scale routine medical-microbiological testing needs to be enhanced. Its clinical value needs to be better defined and requirements for optimal market access and acceptance should be further developed. When forthcoming gAST has been shown to be compatible with insurance and reimbursement budgets as well as microbiological QA/QC assessment and has been through the European Diagnostics Regulation (IVDR) accreditation and/or US FDA approval, only then a more significant future role for gAST can be carefully considered. We should avoid that bureaucracy impedes the development of sequence-based AMR assessment. To date, routine gAST cannot do without combining it with rapid phenotypic AST.