Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance

Shepherd, Matthew J.; Fu, Taoran; Harrington, Niamh E.; Kottara, Anastasia; Cagney, Kendall; Chalmers, James D.; Paterson, Steve; Fothergill, Joanne L.; Brockhurst, Michael A.

doi:10.1038/s41579-024-01041-1

Cited by 7 publications

(1 citation statement)

References 191 publications

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“…Delays in appropriate antimicrobial therapy, often due to bacterial resistance to empiric antibiotic selection, directly correlate with increased in-hospital mortality 4,5 . This can push clinicians toward excessively broad spectrum therapies that may result in worse patient outcomes 6 and the development of resistance 7 , which underscores the broad potential benefits of rapid antimicrobial susceptibility testing (AST) 8,9,10 .…”

Section: Introductionmentioning

confidence: 99%

Clinical Pilot of Bacterial Transcriptional Profiling as a Combined Genotypic and Phenotypic Antimicrobial Susceptibility Test

Young,

Roach,

Martinsen

et al. 2024

Preprint

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Antimicrobial resistance is a growing health threat, but standard methods for determining antibiotic susceptibility are slow and can delay optimal treatment, which is especially consequential in severe infections such as bacteremia. Novel approaches for rapid susceptibility profiling have emerged that characterize either bacterial response to antibiotics (phenotype) or detect specific resistance genes (genotype). GoPhAST-R is a novel assay, performed directly on positive blood cultures, that integrates rapid transcriptional response profiling with detection of key resistance gene transcripts, thereby providing simultaneous data on both phenotype and genotype. Here, we performed the first clinical pilot of GoPhAST-R on 42 positive blood cultures: 26 growing Escherichia coli, 15 growing Klebsiella pneumoniae, and 1 with both. An aliquot of each positive blood culture was exposed to 9 different antibiotics, lysed, then underwent rapid transcriptional profiling on the NanoString® platform; results were analyzed using an in-house susceptibility classification algorithm. GoPhAST-R achieved 95% overall agreement with standard antimicrobial susceptibility testing methods, with the highest agreement for beta-lactams (98%) and the lowest for fluoroquinolones (88%). Epidemic resistance genes including the extended spectrum beta-lactamase blaCTX-M-15and the carbapenemase blaKPCwere also detected within the population. This study demonstrates the clinical feasibility of using transcriptional response profiling for rapid resistance determination, although further validation with larger and more diverse bacterial populations will be essential in future work. GoPhAST-R represents a promising new approach for rapid and comprehensive antibiotic susceptibility testing in clinical settings.

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