Same-day confirmation of infection and antimicrobial susceptibility profiling using flow cytometry.

Anti-Bacterial Agents / therapeutic use Anti-Infective Agents / pharmacology Cohort Studies Flow Cytometry Humans Peritoneal Dialysis / adverse effects Peritonitis / drug therapy
Antimicrobial susceptibility Flow cytometry PD Peritoneal dialysis Peritonitis Rapid diagnostics

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Aug 2022
Historique:
received: 20 02 2022
revised: 21 05 2022
accepted: 21 06 2022
pubmed: 22 7 2022
medline: 17 8 2022
entrez: 21 7 2022
Statut: ppublish

Résumé

The annual mortality burden of antimicrobial resistant infections exceeds 1.27 million/year. With serious infections, every hour without effective antimicrobial therapy results in a 6.7% increased risk of death. New technology that delivers actionable pathology results in clinically-relevant timeframes is an urgent priority. We present the development and validation of an acoustic-enhanced flow cytometric (AFC) workflow that provides same-day confirmation of infection and antimicrobial susceptibility, using peritoneal dialysis (PD)-associated peritonitis as a demonstrative example. In this cohort study, we analysed peritoneal dialysis effluent specimens using AFC to confirm the presence of infection and antimicrobial susceptibility of identified organisms. The primary outcome was the performance of the assay compared to conventional microbiology performed by the clinical laboratory. A secondary outcome was time to result. AFC confirmed infection from primary specimens (n=116), with a sensitivity of 86% and specificity of 94% in ≤ one hour from arrival, including confirmation of infecting organisms in culture-negative cases. Combined with flow-cytometry-assisted antimicrobial susceptibility testing (FAST), we demonstrate same-day antimicrobial susceptibility profiles with an accuracy equivalent to conventional laboratory-based tests. Application of AFC based assays to confirm infection and predict antimicrobial susceptibility can deliver actionable results with a performance that meets or exceeds currently utilised microbiological tests in clinically meaningful timeframes, as demonstrated for PD peritonitis. This technology shows potential for broad applicability to other time-critical serious infections. Government of Western Australia (Department of Health), Government of Australia (National Health and Medical Research Council) and the Forrest Research Foundation.

Sections du résumé

BACKGROUND BACKGROUND
The annual mortality burden of antimicrobial resistant infections exceeds 1.27 million/year. With serious infections, every hour without effective antimicrobial therapy results in a 6.7% increased risk of death. New technology that delivers actionable pathology results in clinically-relevant timeframes is an urgent priority. We present the development and validation of an acoustic-enhanced flow cytometric (AFC) workflow that provides same-day confirmation of infection and antimicrobial susceptibility, using peritoneal dialysis (PD)-associated peritonitis as a demonstrative example.
METHODS METHODS
In this cohort study, we analysed peritoneal dialysis effluent specimens using AFC to confirm the presence of infection and antimicrobial susceptibility of identified organisms. The primary outcome was the performance of the assay compared to conventional microbiology performed by the clinical laboratory. A secondary outcome was time to result.
FINDINGS RESULTS
AFC confirmed infection from primary specimens (n=116), with a sensitivity of 86% and specificity of 94% in ≤ one hour from arrival, including confirmation of infecting organisms in culture-negative cases. Combined with flow-cytometry-assisted antimicrobial susceptibility testing (FAST), we demonstrate same-day antimicrobial susceptibility profiles with an accuracy equivalent to conventional laboratory-based tests.
INTERPRETATION CONCLUSIONS
Application of AFC based assays to confirm infection and predict antimicrobial susceptibility can deliver actionable results with a performance that meets or exceeds currently utilised microbiological tests in clinically meaningful timeframes, as demonstrated for PD peritonitis. This technology shows potential for broad applicability to other time-critical serious infections.
FUNDING BACKGROUND
Government of Western Australia (Department of Health), Government of Australia (National Health and Medical Research Council) and the Forrest Research Foundation.

Identifiants

DOI: 10.1016/j.ebiom.2022.104145 PMID: 35864063 PMC: PMC9386725
pubmed: 35864063
pii: S2352-3964(22)00326-7
doi: 10.1016/j.ebiom.2022.104145
pmc: PMC9386725
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
Anti-Infective Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104145

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Kieran Mulroney (KM), Christine Carson (CC), Teagan Paton (TP), and Timothy Inglis (TI) declare financial interest arising from agreements pertaining to a provisional patent covering part of the work presented in this study. KM, CC, and TI declare loan of flow cytometry equipment and donation of reagents from ThermoFisher Scientific that partially supported the work presented in this study.

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Auteurs

Kieran Mulroney (K)

Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Medicine, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.

Margaret Kopczyk (M)

Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia.

Christine Carson (C)

School of Biomedical Science, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; PathWest Laboratory Medicine WA, PP Block, QEII Medical Centre, Hospital Avenue, Nedlands, WA 6009, Australia.

Teagan Paton (T)

Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; PathWest Laboratory Medicine WA, PP Block, QEII Medical Centre, Hospital Avenue, Nedlands, WA 6009, Australia.

Timothy Inglis (T)

School of Medicine, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; School of Biomedical Science, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; PathWest Laboratory Medicine WA, PP Block, QEII Medical Centre, Hospital Avenue, Nedlands, WA 6009, Australia.

Aron Chakera (A)

Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Medicine, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; Department of Renal Medicine, Sir Charles Gairdner Hospital, QEII Medical Centre, Hospital Avenue, Nedlands, WA 6009, Australia. Electronic address: aron.chakera@uwa.edu.au.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › Same-day confirmation of infection and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Same-day confirmation of infection and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Same-day confirmation of infection and...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytophotométrie › Cytométrie en flux › Same-day confirmation of infection and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Same-day confirmation of infection and...
questionsmedicales.fr › Thérapeutique › Détoxication par sorption › Dialyse rénale › Dialyse péritonéale › Same-day confirmation of infection and...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du péritoine › Péritonite › Same-day confirmation of infection and...