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Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia

Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed...

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Autores principales: Park, Inwon, Kim, Dongsung, Lee, Jae Hyuk, Park, Sung Jin, Jeong, Hwain, Baek, Sumin, Kim, Seonghye, Kim, Serin, Hwang, Ji Eun, Kwon, Hyuksool, Kang, Joo H., Jo, You Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430499/
https://www.ncbi.nlm.nih.gov/pubmed/35862959
http://dx.doi.org/10.1128/spectrum.00864-22
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author Park, Inwon
Kim, Dongsung
Lee, Jae Hyuk
Park, Sung Jin
Jeong, Hwain
Baek, Sumin
Kim, Seonghye
Kim, Serin
Hwang, Ji Eun
Kwon, Hyuksool
Kang, Joo H.
Jo, You Hwan
author_facet Park, Inwon
Kim, Dongsung
Lee, Jae Hyuk
Park, Sung Jin
Jeong, Hwain
Baek, Sumin
Kim, Seonghye
Kim, Serin
Hwang, Ji Eun
Kwon, Hyuksool
Kang, Joo H.
Jo, You Hwan
author_sort Park, Inwon
collection PubMed
description Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed to evaluate the trends of hemodynamics and biomarkers in a porcine bacteremia model treated with insusceptible antibiotics compared to those in susceptible models. Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli, 5.0 * 10^9 CFU) was intravenously administered to 11 male pigs. One hour after bacterial infusion, pigs were assigned to two groups of antibiotics, ceftriaxone (n = 6) or ertapenem (n = 5). Pigs were monitored up to 7 h after bacterial injection with fluid and vasopressor support to maintain the mean arterial blood pressure over 65 mmHg. Blood sampling for blood culture and plasma acquisition was performed before and every predefined hour after E. coli injection. Cytokine (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-8, IL-10, C-reactive protein, procalcitonin, presepsin, heparan sulfate, syndecan, and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) levels in plasma were analyzed using enzyme-linked immunosorbent assays. Bacteremia developed after intravenous injection of E. coli, and negative conversion was confirmed only in the ertapenem group. While trends of other biomarkers failed to show differences, the trend of sTREM-1 was significantly different between the two groups (P = 0.0001, two-way repeated measures analysis of variance). Among hemodynamics and biomarkers, the sTREM-1 level at post 2 h after antibiotics administration represented a significant difference depending on susceptibility, which can be suggested as a biomarker candidate of in vivo antibiotics susceptibility. Further clinical studies are warranted for validation. IMPORTANCE Early and appropriate antibiotic treatment is a keystone in treating patients with sepsis. Despite its importance, blood culture which requires a few days remains as a pillar of diagnostic method for microorganisms and their antibiotic susceptibility. Whether changes in biomarkers and hemodynamics indicate treatment response of susceptible antibiotic compared to resistant one is not well understood to date. In this study using extended-spectrum β-lactamase -producing E. coli bacteremia porcine model, we have demonstrated the comprehensive cardiovascular hemodynamics and trends of plasma biomarkers in sepsis and compared them between two groups with susceptible and resistant antibiotics. While other hemodynamics and biomarkers have failed to differ, we have identified that levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) significantly differed between the two groups over time. Based on the data in this study, trends of sTREM-1 obtained before the antibiotics and 2~4 h after the antibiotics could be a novel host biomarker that triggers the step-up choice of antibiotics.
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spelling pubmed-94304992022-09-01 Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia Park, Inwon Kim, Dongsung Lee, Jae Hyuk Park, Sung Jin Jeong, Hwain Baek, Sumin Kim, Seonghye Kim, Serin Hwang, Ji Eun Kwon, Hyuksool Kang, Joo H. Jo, You Hwan Microbiol Spectr Research Article Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed to evaluate the trends of hemodynamics and biomarkers in a porcine bacteremia model treated with insusceptible antibiotics compared to those in susceptible models. Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli, 5.0 * 10^9 CFU) was intravenously administered to 11 male pigs. One hour after bacterial infusion, pigs were assigned to two groups of antibiotics, ceftriaxone (n = 6) or ertapenem (n = 5). Pigs were monitored up to 7 h after bacterial injection with fluid and vasopressor support to maintain the mean arterial blood pressure over 65 mmHg. Blood sampling for blood culture and plasma acquisition was performed before and every predefined hour after E. coli injection. Cytokine (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-8, IL-10, C-reactive protein, procalcitonin, presepsin, heparan sulfate, syndecan, and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) levels in plasma were analyzed using enzyme-linked immunosorbent assays. Bacteremia developed after intravenous injection of E. coli, and negative conversion was confirmed only in the ertapenem group. While trends of other biomarkers failed to show differences, the trend of sTREM-1 was significantly different between the two groups (P = 0.0001, two-way repeated measures analysis of variance). Among hemodynamics and biomarkers, the sTREM-1 level at post 2 h after antibiotics administration represented a significant difference depending on susceptibility, which can be suggested as a biomarker candidate of in vivo antibiotics susceptibility. Further clinical studies are warranted for validation. IMPORTANCE Early and appropriate antibiotic treatment is a keystone in treating patients with sepsis. Despite its importance, blood culture which requires a few days remains as a pillar of diagnostic method for microorganisms and their antibiotic susceptibility. Whether changes in biomarkers and hemodynamics indicate treatment response of susceptible antibiotic compared to resistant one is not well understood to date. In this study using extended-spectrum β-lactamase -producing E. coli bacteremia porcine model, we have demonstrated the comprehensive cardiovascular hemodynamics and trends of plasma biomarkers in sepsis and compared them between two groups with susceptible and resistant antibiotics. While other hemodynamics and biomarkers have failed to differ, we have identified that levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) significantly differed between the two groups over time. Based on the data in this study, trends of sTREM-1 obtained before the antibiotics and 2~4 h after the antibiotics could be a novel host biomarker that triggers the step-up choice of antibiotics. American Society for Microbiology 2022-07-11 /pmc/articles/PMC9430499/ /pubmed/35862959 http://dx.doi.org/10.1128/spectrum.00864-22 Text en Copyright © 2022 Park et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Park, Inwon
Kim, Dongsung
Lee, Jae Hyuk
Park, Sung Jin
Jeong, Hwain
Baek, Sumin
Kim, Seonghye
Kim, Serin
Hwang, Ji Eun
Kwon, Hyuksool
Kang, Joo H.
Jo, You Hwan
Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia
title Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia
title_full Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia
title_fullStr Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia
title_full_unstemmed Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia
title_short Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia
title_sort changes in biomarkers and hemodynamics according to antibiotic susceptibility in a model of bacteremia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430499/
https://www.ncbi.nlm.nih.gov/pubmed/35862959
http://dx.doi.org/10.1128/spectrum.00864-22
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