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

LYS228 is a novel monobactam with potent activity against LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including carbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant strains tested. O...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2018-10, Vol.62 (10)
Main Authors: Blais, Johanne, Lopez, Sara, Li, Cindy, Ruzin, Alexey, Ranjitkar, Srijan, Dean, Charles R, Leeds, Jennifer A, Casarez, Anthony, Simmons, Robert L, Reck, Folkert
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents
Enterobacteriaceae
Monobactams
Susceptibility
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Summary:LYS228 is a novel monobactam with potent activity against LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including carbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant strains tested. Overall, LYS228 demonstrated potent activity against 271 strains, including multidrug-resistant isolates. Based on MIC values, LYS228 (MIC , 1 μg/ml) was ≥32-fold more active against those strains than were aztreonam, ceftazidime, ceftazidime-avibactam, cefepime, and meropenem. The tigecycline MIC was 4 μg/ml against the strains tested. Against isolates expressing ESBLs ( = 37) or displaying carbapenem resistance ( = 77), LYS228 had MIC values of 1 and 4 μg/ml, respectively. LYS228 exhibited potent bactericidal activity, as indicated by low minimal bactericidal concentration (MBC) to MIC ratios (MBC/MIC ratios of ≤4) against 97.4% of the strains tested (264/271 strains). In time-kill studies, LYS228 consistently achieved reductions in CFU per milliliter of 3 log units (≥99.9% killing) at concentrations ≥4× MIC for and 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.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00552-18