Rapid inference of antibiotic susceptibility phenotype of uropathogens using metagenomic sequencing with neighbor typing.

Autor:	Carroll AC; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Mortimer L; The Eastern Ontario Regional Laboratory, Ottawa, Ontario, Canada., Ghosh H; University of Freiburg, Freiburg, Germany., Reuter S; University of Freiburg, Freiburg, Germany., Grundmann H; University of Freiburg, Freiburg, Germany., Brinda K; Inria, Irisa, Univ. Rennes, Rennes, France., Hanage WP; Harvard T.H Chan School of Public Health, Harvard University, Cambridge, Massachusetts, USA., Li A; Sinai Health, Toronto, Ontario, Canada., Paterson A; Sinai Health, Toronto, Ontario, Canada., Purssell A; The Ottawa Hospital, Ottawa, Ontario, Canada., Rooney A; The University of Toronto, Toronto, Ontario, Canada., Yee NR; The University of Toronto, Toronto, Ontario, Canada.; University Health Network, Toronto, Ontario, Canada., Coburn B; The University of Toronto, Toronto, Ontario, Canada.; University Health Network, Toronto, Ontario, Canada., Able-Thomas S; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia., Antonio M; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia.; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.; Centre for Epidemic Preparedness and Response, London School of Hygiene & Tropical Medicine, London, United Kingdom., McGeer A; Sinai Health, Toronto, Ontario, Canada.; The University of Toronto, Toronto, Ontario, Canada., MacFadden DR; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2024 Nov 29, pp. e0136624. Date of Electronic Publication: 2024 Nov 29.
DOI:	10.1128/spectrum.01366-24
Abstrakt:	Timely diagnostic tools are needed to improve antibiotic treatment. Pairing metagenomic sequencing with genomic neighbor typing algorithms may support rapid clinically actionable results. We created resistance-associated sequence elements (RASE) databases for Escherichia coli and Klebsiella spp . and used them to predict antibiotic susceptibility in directly sequenced (Oxford Nanopore) urine specimens from critically ill patients. RASE analysis was performed on pathogen-specific reads from metagenomic sequencing. We evaluated the ability to predict (i) multi-locus sequence type (MLST) and (ii) susceptibility profiles. We used neighbor typing to predict MLST and susceptibility phenotype of E. coli (64/80) and Klebsiella spp . (16/80) from urine samples. When optimized by lineage score, MLST predictions were concordant for 73% of samples. Similarly, a RASE-susceptible prediction for a given isolate was associated with a specificity and a positive likelihood ratio (LR+) for susceptibility of 0.65 (95% CI, 0.54-0.76) and 2.26 (95% CI, 1.75-2.92), respectively, with an increase in the probability of susceptibility of 10%. A RASE-non-susceptible prediction was associated with a sensitivity and a negative likelihood ratio (LR-) for susceptibility of 0.79 (95% CI, 0.74-0.84) and 0.32 (95% CI, 0.24-0.43) respectively, with a decrease in the probability of susceptibility of 20%. Numerous antibiotic classes could reasonably be reconsidered empiric therapy by shifting empiric probabilities of susceptibility across relevant treatment thresholds. Moreover, these predictions can be available within 6 h. Metagenomic sequencing of urine specimens with neighbor typing provides rapid and informative predictions of lineage and antibiotic susceptibility with the potential to impact clinical decision-making. Importance: Urinary tract infections (UTIs) are a common diagnosis in hospitals and are often treated empirically with broad-spectrum antibiotics. These broad-spectrum agents can select for resistance in these bacteria and co-colonizing organisms. The use of narrow-spectrum agents is desirable as an antibiotic stewardship measure; however, it is counterbalanced by the need for adequate therapy. Identification of causative organisms and their antibiotic susceptibility can help direct treatment; however, conventional testing requires days to produce actionable results. Methods to quickly and accurately predict susceptibility phenotypes for pathogens causing UTI could thus improve both patient outcomes and antibiotic stewardship. Here, expanding on previous work showing accurate prediction for certain Gram-positive pathogens, we demonstrate how the use of RASE from metagenomic sequencing can provide informative and rapid phenotype prediction results for common Gram-negative pathogens in UTI, highlighting the future potential of this method to be used in clinical settings to guide empiric antibiotic selection.
Databáze:	MEDLINE
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