1. In Vitro Activity of a Novel Siderophore-Cephalosporin LCB10-0200 (GT-1), and LCB10-0200/Avibactam, against Carbapenem-Resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa Strains at a Tertiary Hospital in Korea
- Author
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Hyun-Sook Lee, Roshan D'Souza, Kevin Nguyen, Chul Soon Park, Hyun Soo Seo, Le Phuong Nguyen, Thao Nguyen Vu, Richard C. White, Dongeun Yong, Eris Jang, Young Lag Cho, Derrick E. Fouts, An H.T. Pham, Hung Mai, Naina Adren Pinto, and Karrie Goglin
- Subjects
0301 basic medicine ,Klebsiella pneumoniae ,Avibactam ,030106 microbiology ,carbapenem resistance ,Pharmaceutical Science ,Ceftazidime ,Aztreonam ,medicine.disease_cause ,Meropenem ,Article ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmacy and materia medica ,LCB10-0200/Avibactam ,Drug Discovery ,medicine ,polycyclic compounds ,Escherichia coli ,biology ,Pseudomonas aeruginosa ,siderophore-antibiotic conjugate ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,bacterial infections and mycoses ,Acinetobacter baumannii ,RS1-441 ,030104 developmental biology ,chemistry ,Medicine ,Molecular Medicine ,bacteria ,LCB10-0200 (GT-1) ,medicine.drug - 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 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.
- Published
- 2021