Closing the gap in the clinical microbiology lab with next-generation sequencing | ESCMID Global 2026

Abstract: Background: Escalating antimicrobial resistance, persistent gaps in pneumococcal vaccine coverage, and inefficient outbreak investigations continue to challenge clinical microbiology laboratories. Traditional methods often provide delayed or incomplete insight into resistance mechanisms, strain epidemiology, and transmission dynamics. Rapid whole genome sequencing (WGS) offers a unified, high resolution solution with the potential to inform patient care, infection prevention, and institutional decision making within clinically actionable timeframes.

Methods: Three institutional WGS programs were integrated into a consolidated diagnostic model: (1) a 24 hour reflex WGS workflow for unexplained or discordant antimicrobial resistance phenotypes; (2) pneumococcal genotyping using long read WGS with MLST and serotype prediction to inform local vaccination policy; and (3) a taxonomical, stepwise outbreak triage framework combining MALDI TOF, long read WGS, MLST, and cgMLST. Sequencing was performed with Oxford Nanopore, and analyses completed through BugSeq and curated public databases. Results were correlated with susceptibility profiles, vaccine formulations, and infection prevention investigations.

Results: Rapid AMR sequencing identified critical resistance determinants including KPC 31, KPC 45, IMP 18, SHV 12, and porin disruptions, prompting revisions to screening algorithms and empiric escalation strategies. Pneumococcal surveillance identified 16 serotypes and highlighted persistent vaccine covered resistant lineages (19A ST320, 19F ST654) and emerging non vaccine threats such as 35B ST156, guiding institutional vaccination policy. The stepwise outbreak triage workflow resolved four suspected clusters within an average of three days, excluding unrelated Candida auris (via clade typing), Burkholderia cepacia complex isolates (via species confirmation and MLST), and identifying true related isolates only when warranted. Across applications, sequencing averaged $65.