In Vitro Activity of Sulbactam-Durlobactam against Acinetobacter baumannii-calcoaceticus Complex Isolates Collected Globally in 2016 and 2017. 2020

Sarah M McLeod, and Samir H Moussa, and Meredith A Hackel, and Alita A Miller
Entasis Therapeutics, Waltham, Massachusetts, USA sarah.mcleod@entasistx.com.

Acinetobacter baumannii-calcoaceticus complex (ABC) organisms cause severe infections that are difficult to treat due to preexisting antibiotic resistance. Sulbactam-durlobactam (formerly sulbactam-ETX2514) (SUL-DUR) is a β-lactam-β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by ABC organisms, including multidrug-resistant (MDR) strains. The in vitro antibacterial activities of SUL-DUR and comparator agents were determined by broth microdilution against 1,722 clinical isolates of ABC organisms collected in 2016 and 2017 from 31 countries across Asia/South Pacific, Europe, Latin America, the Middle East, and North America. Over 50% of these isolates were resistant to carbapenems. Against this collection of global isolates, SUL-DUR had a MIC50/MIC90 of 1/2 μg/ml compared to a MIC50/MIC90 of 8/64 μg/ml for sulbactam alone. This level of activity was found to be consistent across organisms, regions, sources of infection, and subsets of resistance phenotypes, including MDR and extensively drug-resistant isolates. The SUL-DUR activity was superior to those of the tested comparators, with only colistin having similar potency. Whole-genome sequencing of the 39 isolates (2.3%) with a SUL-DUR MIC of >4 μg/ml revealed that these strains encoded either the metallo-β-lactamase NDM-1, which durlobactam does not inhibit, or single amino acid substitutions near the active site of penicillin binding protein 3 (PBP3), the primary target of sulbactam. In summary, SUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC organisms, including MDR isolates.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073336 Whole Genome Sequencing Techniques to determine the entire sequence of the GENOME of an organism or individual. Complete Genome Sequencing,Genome Sequencing, Complete,Genome Sequencing, Whole,Sequencing, Complete Genome,Sequencing, Whole Genome
D000150 Acinetobacter A genus of gram-negative bacteria of the family MORAXELLACEAE, found in soil and water and of uncertain pathogenicity. Herellea,Mima
D000151 Acinetobacter Infections Infections with bacteria of the genus ACINETOBACTER. Mimae Infections,Infections, Acinetobacter,Infections, Mimae,Acinetobacter Infection,Infection, Acinetobacter,Infection, Mimae,Mimae Infection
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D013407 Sulbactam A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone. Bétamaze,CP-45899,Combactam,Penicillanic Acid Sulfone,Sulbactam Sodium,CP 45899,CP45899,Sodium, Sulbactam,Sulfone, Penicillanic Acid
D017714 Community-Acquired Infections Any infection acquired in the community, that is, contrasted with those acquired in a health care facility (CROSS INFECTION). An infection would be classified as community-acquired if the patient had not recently been in a health care facility or been in contact with someone who had been recently in a health care facility. Community Acquired Infection,Community-Acquired Infection,Infections, Community-Acquired,Acquired Infection, Community,Acquired Infections, Community,Community Acquired Infections,Infection, Community Acquired,Infection, Community-Acquired,Infections, Community Acquired
D053961 Azabicyclo Compounds Bicyclic bridged compounds that contain a nitrogen which has three bonds. The nomenclature indicates the number of atoms in each path around the rings, such as [2.2.2] for three equal length paths. Some members are TROPANES and BETA LACTAMS. Azabicyclo(1.1.0)Butanes,Azabicyclo(2.2.2)Octanes,Azabicyclo(3.3.1)Nonanes,Azabicyclo(4.3.0)Nonanes,Azabicyclo(5.2.2)Undecanes

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