期刊
PHARMACEUTICALS
卷 14, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ph14040370
关键词
carbapenem resistance; Avibactam; siderophore-antibiotic conjugate
资金
- BioNano Health-Guard Research Center - Ministry of Science, ICT & Future Planning (MSIP) of Korea as a Global Frontier Project [HGUARD_2014M3A6B2060509]
- Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agricultural Microbiome R&D Program - Ministry of Agriculture, Food and Rural Affairs (MAFRA) [918003-4]
- National Institute of Health, Korea [2019ER540300R514931]
- National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Department of Health and Human Services [U19AI110819]
- Brain Korea 21 plus Project for Medical Science, Yonsei University
The siderophore-antibiotic conjugate LCB10-0200, in combination with AVI, shows promising activity against carbapenem-resistant E. coli and K. pneumoniae. However, its effectiveness is limited in A. baumannii and P. aeruginosa. The addition of AVI significantly enhances the activity of LCB10-0200 against carbapenem-resistant strains, but not in all cases.
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 LCB10-0200 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. LCB10-0200 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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