In Vitro Activity of a Novel Siderophore-Cephalosporin LCB10-0200 (GT-1), and LCB10-0200/Avibactam, against Carbapenem-Resistant <em>Escherichia coli</em>, <em>Klebsiella pneumoniae</em>, <em>Acinetobacter baumannii</em>, and <em>Pseudomonas aeruginosa</em> Strains at a Tertiary Hospital in Korea

• Main Authors: Le Phuong Nguyen (Author), Chul Soon Park (Author), Naina Adren Pinto (Author), Hyunsook Lee (Author), Hyun Soo Seo (Author), Thao Nguyen Vu (Author), Hung Mai (Author), An H. T. Pham (Author), Eris Jang (Author), Young Lag Cho (Author), Karrie Goglin (Author), Kevin Nguyen (Author), Richard White (Author), Roshan D'Souza (Author), Derrick E. Fouts (Author), Dongeun Yong (Author)
• Format: Book
• Published: MDPI AG, 2021-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph14040370; 1424-8247
• Keywords: carbapenem resistance; LCB10-0200 (GT-1); LCB10-0200/Avibactam; siderophore-antibiotic conjugate; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 14, Iss 4, p 370 (2021)

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 <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, and <i>Pseudomonas aeruginosa</i>. 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 <i>E. coli</i> and <i>K. pneumoniae</i>, 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 <i>A. baumannii</i> and <i>P. aeruginosa</i> 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 <i>E. coli</i> and <i>K. pneumoniae</i>, while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing <i>A. baumannii</i> and <i>P. aeruginosa</i>. 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 <i>E. coli</i>, <i>K. pneumoniae</i>.