A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing

ABSTRACT Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality. To this end, we have developed a multiplex fluidic chip for rapid phenotypic antibiotic susceptibilit...

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Autores principales: Pikkei Wistrand-Yuen, Christer Malmberg, Nikos Fatsis-Kavalopoulos, Moritz Lübke, Thomas Tängdén, Johan Kreuger
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:cd2109e2d337444da3fa1a0aa15063c22021-11-15T15:56:57ZA Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing10.1128/mBio.03109-192150-7511https://doaj.org/article/cd2109e2d337444da3fa1a0aa15063c22020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03109-19https://doaj.org/toc/2150-7511ABSTRACT Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality. To this end, we have developed a multiplex fluidic chip for rapid phenotypic antibiotic susceptibility testing of bacteria. A total of 21 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were acquired from the EUCAST Development Laboratory and tested against amikacin, ceftazidime, and meropenem (Gram-negative bacteria) or gentamicin, ofloxacin, and tetracycline (Gram-positive bacteria). The bacterial samples were mixed with agarose and loaded in an array of growth chambers in the chip where bacterial microcolony growth was monitored over time using automated image analysis. MIC values were automatically obtained by tracking the growth rates of individual microcolonies in different regions of antibiotic gradients. Stable MIC values were obtained within 2 to 4 h, and the results showed categorical agreement with reference MIC values as determined by broth microdilution in 86% of the cases. IMPORTANCE Prompt and effective antimicrobial therapy is crucial for the management of patients with severe bacterial infections but is becoming increasingly difficult to provide due to emerging antibiotic resistance. The traditional methods for antibiotic susceptibility testing (AST) used in most clinical laboratories are reliable but slow with turnaround times of 2 to 3 days, which necessitates the use of empirical therapy with broad-spectrum antibiotics. There is a great need for fast and reliable AST methods that enable starting targeted treatment within a few hours to improve patient outcome and reduce the overuse of broad-spectrum antibiotics. The multiplex fluidic chip for phenotypic AST described in the present study may enable data on antimicrobial resistance within 2 to 4 h, allowing for an early initiation of appropriate antibiotic therapy.Pikkei Wistrand-YuenChrister MalmbergNikos Fatsis-KavalopoulosMoritz LübkeThomas TängdénJohan KreugerAmerican Society for Microbiologyarticleantibiotic susceptibility testingclinical isolatesfluidic chipmicrofluidicsmultiplexMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution DOAJ
collection DOAJ
language EN
topic antibiotic susceptibility testing
clinical isolates
fluidic chip
microfluidics
multiplex
Microbiology
QR1-502
spellingShingle antibiotic susceptibility testing
clinical isolates
fluidic chip
microfluidics
multiplex
Microbiology
QR1-502
Pikkei Wistrand-Yuen
Christer Malmberg
Nikos Fatsis-Kavalopoulos
Moritz Lübke
Thomas Tängdén
Johan Kreuger
A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
description ABSTRACT Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality. To this end, we have developed a multiplex fluidic chip for rapid phenotypic antibiotic susceptibility testing of bacteria. A total of 21 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were acquired from the EUCAST Development Laboratory and tested against amikacin, ceftazidime, and meropenem (Gram-negative bacteria) or gentamicin, ofloxacin, and tetracycline (Gram-positive bacteria). The bacterial samples were mixed with agarose and loaded in an array of growth chambers in the chip where bacterial microcolony growth was monitored over time using automated image analysis. MIC values were automatically obtained by tracking the growth rates of individual microcolonies in different regions of antibiotic gradients. Stable MIC values were obtained within 2 to 4 h, and the results showed categorical agreement with reference MIC values as determined by broth microdilution in 86% of the cases. IMPORTANCE Prompt and effective antimicrobial therapy is crucial for the management of patients with severe bacterial infections but is becoming increasingly difficult to provide due to emerging antibiotic resistance. The traditional methods for antibiotic susceptibility testing (AST) used in most clinical laboratories are reliable but slow with turnaround times of 2 to 3 days, which necessitates the use of empirical therapy with broad-spectrum antibiotics. There is a great need for fast and reliable AST methods that enable starting targeted treatment within a few hours to improve patient outcome and reduce the overuse of broad-spectrum antibiotics. The multiplex fluidic chip for phenotypic AST described in the present study may enable data on antimicrobial resistance within 2 to 4 h, allowing for an early initiation of appropriate antibiotic therapy.
format article
author Pikkei Wistrand-Yuen
Christer Malmberg
Nikos Fatsis-Kavalopoulos
Moritz Lübke
Thomas Tängdén
Johan Kreuger
author_facet Pikkei Wistrand-Yuen
Christer Malmberg
Nikos Fatsis-Kavalopoulos
Moritz Lübke
Thomas Tängdén
Johan Kreuger
author_sort Pikkei Wistrand-Yuen
title A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
title_short A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
title_full A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
title_fullStr A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
title_full_unstemmed A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
title_sort multiplex fluidic chip for rapid phenotypic antibiotic susceptibility testing
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/cd2109e2d337444da3fa1a0aa15063c2
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