In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea

Le Phuong Nguyen; Chul Soon Park; Naina Adren Pinto; Hyunsook Lee; Hyun Soo Seo; Thao Nguyen Vu; Hung Mai; An H.T. Pham; Eris Jang; Young Lag Cho; Karrie Goglin; Kevin Nguyen; Richard White; Roshan D’souza; Derrick E. Fouts; Dongeun Yong

doi:10.3390/ph14040370

In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea

Le Phuong Nguyen, Chul Soon Park, Naina Adren Pinto, Hyunsook Lee, Hyun Soo Seo, Thao Nguyen Vu, Hung Mai, An H.T. Pham, Eris Jang, Young Lag Cho, Karrie Goglin, Kevin Nguyen, Richard White, Roshan D’souza, Derrick E. Fouts, Dongeun Yong

Department of Laboratory Medicine

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB100200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB100200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC-producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA, and VIM-producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP-and NDM-producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.

Original language	English
Article number	370
Journal	Pharmaceuticals
Volume	14
Issue number	4
DOIs	https://doi.org/10.3390/ph14040370
Publication status	Published - 2021 Apr

Bibliographical note

Funding Information:
This work was supported by the BioNano Health-Guard Research Center funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea as a Global Frontier Project (HGUARD_2014M3A6B2060509); by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agricultural Microbiome R&D Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA)(918003-4); by a grant from the National Institute of Health, Korea (2019ER540300R514931). This work was also funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Department of Health and Human Services under award number U19AI110819 and by the Brain Korea 21 plus Project for Medical Science, Yonsei University.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

Molecular Medicine
Pharmaceutical Science
Drug Discovery

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Nguyen, L. P., Park, C. S., Pinto, N. A., Lee, H., Seo, H. S., Vu, T. N., Mai, H., Pham, A. H. T., Jang, E., Cho, Y. L., Goglin, K., Nguyen, K., White, R., D’souza, R., Fouts, D. E., & Yong, D. (2021). In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea. Pharmaceuticals, 14(4), [370]. https://doi.org/10.3390/ph14040370

Nguyen, Le Phuong ; Park, Chul Soon ; Pinto, Naina Adren et al. / In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea. In: Pharmaceuticals. 2021 ; Vol. 14, No. 4.

@article{5b9710e3c7854d878ddc450ad6d16e3b,

title = "In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea",

abstract = "The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB100200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB100200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC-producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA, and VIM-producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP-and NDM-producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.",

author = "Nguyen, {Le Phuong} and Park, {Chul Soon} and Pinto, {Naina Adren} and Hyunsook Lee and Seo, {Hyun Soo} and Vu, {Thao Nguyen} and Hung Mai and Pham, {An H.T.} and Eris Jang and Cho, {Young Lag} and Karrie Goglin and Kevin Nguyen and Richard White and Roshan D{\textquoteright}souza and Fouts, {Derrick E.} and Dongeun Yong",

note = "Funding Information: This work was supported by the BioNano Health-Guard Research Center funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea as a Global Frontier Project (HGUARD_2014M3A6B2060509); by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agricultural Microbiome R&D Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA)(918003-4); by a grant from the National Institute of Health, Korea (2019ER540300R514931). This work was also funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Department of Health and Human Services under award number U19AI110819 and by the Brain Korea 21 plus Project for Medical Science, Yonsei University. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = apr,

doi = "10.3390/ph14040370",

language = "English",

volume = "14",

journal = "Pharmaceuticals",

issn = "1424-8247",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

}

Nguyen, LP, Park, CS, Pinto, NA, Lee, H, Seo, HS, Vu, TN, Mai, H, Pham, AHT, Jang, E, Cho, YL, Goglin, K, Nguyen, K, White, R, D’souza, R, Fouts, DE & Yong, D 2021, 'In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea', Pharmaceuticals, vol. 14, no. 4, 370. https://doi.org/10.3390/ph14040370

In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea. / Nguyen, Le Phuong; Park, Chul Soon; Pinto, Naina Adren et al.
In: Pharmaceuticals, Vol. 14, No. 4, 370, 04.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea

AU - Nguyen, Le Phuong

AU - Park, Chul Soon

AU - Pinto, Naina Adren

AU - Lee, Hyunsook

AU - Seo, Hyun Soo

AU - Vu, Thao Nguyen

AU - Mai, Hung

AU - Pham, An H.T.

AU - Jang, Eris

AU - Cho, Young Lag

AU - Goglin, Karrie

AU - Nguyen, Kevin

AU - White, Richard

AU - D’souza, Roshan

AU - Fouts, Derrick E.

AU - Yong, Dongeun

N1 - Funding Information: This work was supported by the BioNano Health-Guard Research Center funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea as a Global Frontier Project (HGUARD_2014M3A6B2060509); by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agricultural Microbiome R&D Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA)(918003-4); by a grant from the National Institute of Health, Korea (2019ER540300R514931). This work was also funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Department of Health and Human Services under award number U19AI110819 and by the Brain Korea 21 plus Project for Medical Science, Yonsei University. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/4

Y1 - 2021/4

N2 - The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB100200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB100200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC-producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA, and VIM-producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP-and NDM-producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.

AB - The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB100200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB100200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC-producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA, and VIM-producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP-and NDM-producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.

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Nguyen LP, Park CS, Pinto NA, Lee H, Seo HS, Vu TN et al. In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea. Pharmaceuticals. 2021 Apr;14(4):370. doi: 10.3390/ph14040370

In vitro activity of a novel siderophore-cephalosporin LCB10-0200 (GT-1), and LCB10-0200/avibactam, against carbapenem-resistant Escherichia coli, Llebsiella pneumoniae, Acinetobacter baumannii, and pseudomonas aeruginosa strains at a tertiary hospital in Korea

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