Nguyen Le Phuong, Park Chul Soon, Pinto Naina Adren, Lee Hyunsook, Seo Hyun Soo, Vu Thao Nguyen, Mai Hung, Pham An H T, Jang Eris, Cho Young Lag, Goglin Karrie, Nguyen Kevin, White Richard, D'Souza Roshan, Fouts Derrick E, Yong Dongeun
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul 03722, Korea.
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea.
Pharmaceuticals (Basel). 2021 Apr 16;14(4):370. doi: 10.3390/ph14040370.
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 , , , and . 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 and , 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 and 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 and , while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing and . 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 , .
铁载体-抗生素共轭物LCB10-0200（又名GT-1）已被开发用于对抗多重耐药革兰氏阴性菌。在本研究中，研究了LCB10-0200和LCB10-0200/阿维巴坦（AVI）对耐碳青霉烯类的[具体细菌种类1]、[具体细菌种类2]、[具体细菌种类3]和[具体细菌种类4]的体外活性。使用琼脂稀释法测定了LCB10-0200、LCB10-0200/AVI、氨曲南、氨曲南/AVI、头孢他啶、头孢他啶/AVI和美罗培南的最低抑菌浓度（MIC）。使用Illumina进行全基因组测序并分析耐药基因组。LCB10-0200在耐美罗培南的[具体细菌种类1]和[具体细菌种类2]中显示出比对照药物更强的活性，并且添加AVI可将LCB10-0200的活性提高至90.5%的分离株的MIC≤0.12mg/L。相比之下，虽然单独的LCB10-0200对耐美罗培南的[具体细菌种类1]和[具体细菌种类丝]显示出强大活性，84.3%的分离株的MIC≤4mg/L，但与AVI联合使用并未提高其活性。LCB10-0200/AVI对产生CTX-M、SHV、CMY和KPC的[具体细菌种类1]和[具体细菌种类2]有活性，而单独的LCB10-0200对产生ADC、OXA和VIM的[具体细菌种类1]和[具体细菌种类2]有活性。LCB10-0200和LCB10-0200/AVI对产生IMP和NDM的菌株均显示出低活性。单独的LCB10-0200对选定菌株表现出强大活性。添加AVI显著增加了LCB10-0200对耐碳青霉烯类的[具体细菌种类1]、[具体细菌种类2]的活性。
