A5084120016- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Use and Resistance
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- RNA and protein synthesis mechanisms
- Pneumonia and Respiratory Infections
- Bacteriophages and microbial interactions
- Berberine and alkaloids research
- Pharmaceutical and Antibiotic Environmental Impacts
- Genomics and Chromatin Dynamics
- Escherichia coli research studies
- Salmonella and Campylobacter epidemiology
- DNA and Nucleic Acid Chemistry
- Pneumocystis jirovecii pneumonia detection and treatment
- Microbial Natural Products and Biosynthesis
- Art Therapy and Mental Health
- Dispute Resolution and Class Actions
- Multi-Agent Systems and Negotiation
- Cystic Fibrosis Research Advances
- Virtual Reality Applications and Impacts
- Infections and bacterial resistance
- Hepatitis B Virus Studies
- Bacillus and Francisella bacterial research
- Bacterial Infections and Vaccines
Innoviva (United States)
2023-2025
Entasis Therapeutics (United States)
2016-2024
McGill University
2022
Mitre (United States)
2022
Saarland University
2019
AstraZeneca (United States)
2011-2017
AstraZeneca (United Kingdom)
2014
Bioscience (China)
2014
MacEwan University
2012
NHS Highland
2012
A high-throughput phenotypic screen based on a Citrobacter freundii AmpC reporter expressed in Escherichia coli was executed to discover novel inhibitors of bacterial cell wall synthesis, an attractive, well-validated target for antibiotic intervention. Here we describe the discovery and characterization sulfonyl piperazine pyrazole compounds, each with mechanisms action. E. mutants resistant these compounds display no cross-resistance antibiotics other classes. Resistance maps LpxH, which...
Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination designed to treat serious Acinetobacter baumannii -calcoaceticus complex (ABC) infections, including carbapenem-non-susceptible and multidrug-resistant (MDR) isolates. The current study characterized the in vitro activity of sulbactam-durlobactam against collection 5,032 ABC clinical isolates collected 33 countries across Asia/South Pacific region, Europe, Latin America, Middle East, North America from 2016 2021.
Sulbactam–durlobactam is a pathogen-targeted β-lactam/β-lactamase inhibitor combination that has been approved by the US FDA for treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused susceptible isolates Acinetobacter baumannii–calcoaceticus complex (ABC) in patients 18 years age older. Sulbactam penicillin derivative with antibacterial activity against but prone to hydrolysis β-lactamases encoded contemporary isolates. Durlobactam diazabicyclooctane β-lactamase...
In Gram-negative bacteria, lipoproteins are transported to the outer membrane by Lol system. this process, released from inner ABC transporter LolCDE and passed LolA, a diffusible periplasmic molecular chaperone. Lipoproteins then transferred receptor protein, LolB, for insertion in membrane. Here we describe discovery characterization of novel pyridineimidazole compounds that inhibit process. Escherichia coli mutants resistant pyridineimidazoles show no cross-resistance other classes...
Acinetobacter baumannii-calcoaceticus complex (ABC) organisms cause severe infections that are difficult to treat due preexisting antibiotic resistance. Sulbactam-durlobactam (formerly sulbactam-ETX2514) (SUL-DUR) is a β-lactam-β-lactamase inhibitor combination designed serious caused by ABC organisms, including multidrug-resistant (MDR) strains. The in vitro antibacterial activities of SUL-DUR and comparator agents were determined broth microdilution against 1,722 clinical isolates...
Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases responsible for a large proportion of the phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with antibiotics negate action β-lactamases, thereby restoring activity β-lactam. Newly developed BLIs offer some advantage over older terms enzymatic spectrum but limited...
Abstract Sulbactam-durlobactam is a pathogen-targeted β-lactam/β-lactamase inhibitor combination in late-stage development for the treatment of Acinetobacter infections, including those caused by multidrug-resistant strains. Durlobactam member diazabicyclooctane class β-lactamase inhibitors with broad-spectrum serine activity. Sulbactam first-generation, narrow-spectrum that also has intrinsic antibacterial activity against spp. due to its ability inhibit penicillin-binding proteins 1 and 3....
Abstract Disconnections between in vitro responses and those observed whole cells confound many attempts to design drugs areas of serious medical need. A method based on 1D 1 H NMR spectroscopy is reported that affords the ability monitor hydrolytic decomposition carbapenem antibiotic meropenem inside Escherichia coli expressing New Delhi metallo‐β‐lactamase subclass (NDM‐1), an emerging antibiotic‐resistance threat. Cell‐based studies demonstrated two known NDM‐1 inhibitors, L ‐captopril...
ABSTRACT The novel diazabicyclooctenone ETX2514 is a potent, broad-spectrum serine β-lactamase inhibitor that restores sulbactam activity against resistant Acinetobacter baumannii . frequency of spontaneous resistance to sulbactam-ETX2514 in clinical isolates was found be 7.6 × 10 −10 <9.0 at 4× MIC and mapped residues near the active site penicillin binding protein 3 (PBP3). Purified mutant PBP3 proteins demonstrated reduced affinity for sulbactam. In sulbactam-sensitive isolate, also...
ABSTRACT Acinetobacter baumannii - calcoaceticus complex (ABC) causes severe infections that are difficult to treat due pre-existing antibiotic resistance. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination designed serious caused by , including multidrug- and carbapenem-resistant strains. In recent global surveillance study of 5,032 ABC clinical isolates collected from 2016 2021, less than 2% had SUL-DUR MIC values >4 µg/mL. Molecular...
ABSTRACT Acinetobacter baumannii-calcoaceticu s complex (ABC) causes severe, difficult-to-treat infections that are frequently antibiotic resistant. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination designed to treat ABC infections, including those caused by multidrug-resistant strains. In global, pathogen-specific, randomized, controlled phase 3 trial (ATTACK), the efficacy and safety of SUL-DUR were compared colistin, both dosed with...
ABSTRACT Infections caused by Acinetobacter baumannii are increasingly multidrug resistant and associated with high rates of morbidity mortality. Sulbactam is a β-lactamase inhibitor intrinsic antibacterial activity against A. . Durlobactam non-β-lactam an extended spectrum compared to other inhibitors its class. In vitro pharmacodynamic infection models were undertaken establish the pharmacokinetic/pharmacodynamic (PK/PD) index magnitudes sulbactam durlobactam efficacy simulate epithelial...
Abstract Background Zoliflodacin is an oral, single-dose, first-in-class spiropyrimidinetrione bacterial topoisomerase inhibitor with activity against multidrug-resistant strains of Neisseria gonorrhoeae. Efficacy and safety zoliflodacin for the treatment uncomplicated gonorrhea was studied in a global Phase 3 trial that demonstrated non-inferiority to ceftriaxone plus azithromycin. In this study, antibiotic susceptibility baseline N. gonorrhoeae isolates from US participants characterized....
Abstract Background Eravacycline is a fully synthetic, fluorocycline antibiotic approved for the treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years age Europe, Singapore, China, Taiwan, Hong Kong, US and UK. The purpose this study was to monitor vitro activity eravacycline against isolates collected from global surveillance 2018-2022. A total 35,336 were which data 23,127 comprising Staphylococcus aureus (including methicillin-resistant S. aureus, MRSA),...
Vibrio cholerae, the cause of cholera, has two circular chromosomes. The parAB genes on each V. cholerae chromosome act to control segregation in a replicon-specific fashion. I (ChrI) (parAB1) govern localization origin region ChrI, while II (ChrII) (parAB2) ChrII. In addition ParA and ParB proteins, Par systems require binding sites (parS). Here we identified parS both We found three clustered origin-proximal ParB1 parS1 ChrI. Deletion these abrogated yellow fluorescent protein (YFP)-ParB1...
Multi-drug-resistant Enterobacteriales expressing a wide array of β-lactamases are emerging as global health threat in both hospitals and communities. Although several intravenous drugs have recently been approved to address this need, there no oral Gram-negative agents that safe broadly effective against such pathogens. The lack an agent is concern for common infections which could otherwise be treated the community but, due antibiotic resistance, require hospitalization allow therapy....
Summary CTXφ is a filamentous bacteriophage that encodes cholera toxin and integrates site‐specifically into the larger of two Vibrio cholerae chromosomes. The genome lacks an integrase; instead, its integration depends on chromosome‐encoded tyrosine recombinases XerC XerD. During integration, recombination occurs between regions homology in V. chromosome. Here, we define elements phage ( attP ) bacterial chromosome attB required for integration. short sequence composed one binding site XerD...