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

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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 languageEnglish
Article number370
JournalPharmaceuticals
Volume14
Issue number4
DOIs
Publication statusPublished - 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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