Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

In Vitro Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-resistant Enterobacteriaceae

Blais, Johanne, Lopez, Sara, Li, Cindy, Ruzin, Alexey, Ranjikar, Srijan, Dean, Charles, Leeds, Jennifer, Casarez, Anthony, Simmons, Bob and Reck, Folkert (2018) In Vitro Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-resistant Enterobacteriaceae. Antimicrobial agents and chemotherapy. ISSN 1098-6596


LYS228 is a novel monobactam with potent activity against Enterobacteriaceae. LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including Klebsiella pneumoniae carbapenemases (KPCs), resulting in potency against the majority of extended spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE) strains tested. Overall, LYS228 demonstrated potent activity against 271 Enterobacteriaceae strains, including multidrug-resistant isolates. Based upon MIC90 values, LYS228 (MIC90= 1 μg/mL) was ≥32-fold more active against these strains than were aztreonam, ceftazidime, ceftazidime/avibactam, cefepime, and meropenem. The MIC90 value for tigecyline was 4 μg/mL against the strains tested. Against Enterobacteriaceae isolates expressing ESBLs (N=37) or displaying carbapenem resistance (N=77), LYS228 had MIC90 values of 1 and 4 µg/mL, respectively.
LYS228 exhibited potent bactericidal activity as indicated by low MBC to MIC ratios (≤4) against 97.4% (264/271) of the Enterobacteriaceae strains tested. In time-kill studies, LYS228 consistently achieved 3-log10 reduction in colony-forming units (CFU)/mL (≥99.9% killing) at concentrations ≥4X the MIC for E. coli and K. pneumoniae reference strains as well as isolates encoding TEM-1, SHV-1, CTX-M-14, CTX-M-15, KPC-2, KPC-3 and NDM-1 β-lactamases.

Item Type: Article
Date Deposited: 01 Sep 2018 00:45
Last Modified: 01 Sep 2018 00:45


Email Alerts

Register with OAK to receive email alerts for saved searches.