Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates

Abstract Bacteremia is a life-threatening condition for which antibiotics must be prescribed within hours of clinical diagnosis. Since the current gold standard for bacteremia diagnosis is based on conventional methods developed in the mid-1800s—growth on agar or in broth—identification and suscepti...

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Autores principales:	Maxim Kalashnikov, Marc Mueller, Christine McBeth, Jean C. Lee, Jennifer Campbell, Andre Sharon, Alexis F. Sauer-Budge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d306b4cafa404577b5d00196e2e8c32f
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spelling	oai:doaj.org-article:d306b4cafa404577b5d00196e2e8c32f2021-12-02T16:06:56ZRapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates10.1038/s41598-017-07584-z2045-2322https://doaj.org/article/d306b4cafa404577b5d00196e2e8c32f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07584-zhttps://doaj.org/toc/2045-2322Abstract Bacteremia is a life-threatening condition for which antibiotics must be prescribed within hours of clinical diagnosis. Since the current gold standard for bacteremia diagnosis is based on conventional methods developed in the mid-1800s—growth on agar or in broth—identification and susceptibility profiling for both Gram-positive and Gram-negative bacterial species requires at least 48–72 h. Recent advancements in accelerated phenotypic antibiotic susceptibility testing have centered on the microscopic growth analysis of small bacterial populations. These approaches are still inherently limited by the bacterial growth rate. Our approach is fundamentally different. By applying environmental stress to bacteria in a microfluidic platform, we can correctly assign antibiotic susceptibility profiles of clinically relevant Gram-negative bacteria within two hours of antibiotic introduction rather than 8–24 h. The substantial expansion to include a number of clinical isolates of important Gram-negative species—Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa—reported here underscores the broad utility of our approach, complementing the method’s proven utility for Gram-positive bacteria. We also demonstrate that the platform is compatible with antibiotics that have varying mechanisms of action—meropenem, gentamicin, and ceftazidime—highlighting the versatility of this platform.Maxim KalashnikovMarc MuellerChristine McBethJean C. LeeJennifer CampbellAndre SharonAlexis F. Sauer-BudgeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maxim Kalashnikov Marc Mueller Christine McBeth Jean C. Lee Jennifer Campbell Andre Sharon Alexis F. Sauer-Budge Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
description	Abstract Bacteremia is a life-threatening condition for which antibiotics must be prescribed within hours of clinical diagnosis. Since the current gold standard for bacteremia diagnosis is based on conventional methods developed in the mid-1800s—growth on agar or in broth—identification and susceptibility profiling for both Gram-positive and Gram-negative bacterial species requires at least 48–72 h. Recent advancements in accelerated phenotypic antibiotic susceptibility testing have centered on the microscopic growth analysis of small bacterial populations. These approaches are still inherently limited by the bacterial growth rate. Our approach is fundamentally different. By applying environmental stress to bacteria in a microfluidic platform, we can correctly assign antibiotic susceptibility profiles of clinically relevant Gram-negative bacteria within two hours of antibiotic introduction rather than 8–24 h. The substantial expansion to include a number of clinical isolates of important Gram-negative species—Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa—reported here underscores the broad utility of our approach, complementing the method’s proven utility for Gram-positive bacteria. We also demonstrate that the platform is compatible with antibiotics that have varying mechanisms of action—meropenem, gentamicin, and ceftazidime—highlighting the versatility of this platform.
format	article
author	Maxim Kalashnikov Marc Mueller Christine McBeth Jean C. Lee Jennifer Campbell Andre Sharon Alexis F. Sauer-Budge
author_facet	Maxim Kalashnikov Marc Mueller Christine McBeth Jean C. Lee Jennifer Campbell Andre Sharon Alexis F. Sauer-Budge
author_sort	Maxim Kalashnikov
title	Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
title_short	Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
title_full	Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
title_fullStr	Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
title_full_unstemmed	Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
title_sort	rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of gram-negative clinical isolates
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d306b4cafa404577b5d00196e2e8c32f
work_keys_str_mv	AT maximkalashnikov rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates AT marcmueller rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates AT christinemcbeth rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates AT jeanclee rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates AT jennifercampbell rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates AT andresharon rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates AT alexisfsauerbudge rapidphenotypicstressbasedmicrofluidicantibioticsusceptibilitytestingofgramnegativeclinicalisolates
_version_	1718384808023818240

Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates

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