ArticleAntimicrobial agents and chemotherapy2016
Distinctive Binding of Avibactam to Penicillin-Binding Proteins of Gram-Negative and Gram-Positive Bacteria.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Deep learning recognises antibiotic modes of action from brightfield images.Nature communications · 2026Article
- A genomics-informed mechanism-based pharmacokinetic/pharmacodynamic model of cefiderocol and ceftazidime/avibactam against carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Structural perspectives on clinical β-lactamase inhibitors: From mechanism to resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- Boronate-Based Inhibitors of Penicillin-Binding Proteins: An Underestimated Avenue for Antibiotic Discovery?Pharmaceuticals (Basel, Switzerland) · 2025Article
- Rapid emergence of resistance to broad-spectrum direct antimicrobial activity of avibactam.Microbiology spectrum · 2025Article
- Article
- Potential role of avibactam in restoring susceptibility in Escherichia coli with two copies of blaScientific reports · 2025Article
- Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms.Archives of microbiology · 2025Review
- Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare.The Journal of antimicrobial chemotherapy · 2024Review
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Using host-mimicking conditions and a murine cutaneous abscess model to identify synergistic antibiotic combinations effective againstFrontiers in cellular and infection microbiology · 2024Article
- Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- Detecting KPC-2 and NDM-1 Coexpression in Klebsiella pneumoniae Complex from Human and Animal Hosts in South America.Microbiology spectrum · 2022Article
- Intrinsic Antibacterial Activity of XeruborbactamAntimicrobial agents and chemotherapy · 2022Article
- Synergy between Mecillinam and Ceftazidime/Avibactam or Avibactam against Multi-Drug-Resistant Carbapenemase-ProducingAntibiotics (Basel, Switzerland) · 2022Article
- Live-Cell Profiling of Penicillin-Binding Protein Inhibitors inACS infectious diseases · 2022Article
- Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing.Antibiotics (Basel, Switzerland) · 2022Review
- Structural Characterization of the D179N and D179Y Variants of KPC-2 β-Lactamase: Ω-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam.Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Avibactam is a novel non-β-lactam β-lactamase inhibitor that covalently acylates a variety of β-lactamases, causing inhibition. Although avibactam presents limited antibacterial activity, its acylation ability toward bacterial penicillin-binding proteins (PBPs) was investigated. Staphylococcus aureus was of particular interest due to the reported β-lactamase activity of PBP4. The binding of avibactam to PBPs was measured by adding increasing concentrations to membrane preparations of a variety of Gram-positive and Gram-negative bacteria prior to addition of the fluorescent reagent Bocillin FL. Relative binding (measured here as the 50% inhibitory concentration [IC50]) to PBPs was estimated by quantification of fluorescence after gel electrophoresis. Avibactam was found to selectively bind to some PBPs. In Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, and S. aureus, avibactam primarily bound to PBP2, with IC50s of 0.92, 1.1, 3.0, and 51 μg/ml, respectively, whereas binding to PBP3 was observed in Streptococcus pneumoniae (IC50, 8.1 μg/ml). Interestingly, avibactam was able to significantly enhance labeling of S. aureus PBP4 by Bocillin FL. In PBP competition assays with S. aureus, where avibactam was used at a fixed concentration in combination with varied amounts of ceftazidime, the apparent IC50 of ceftazidime was found to be very similar to that determined for ceftazidime when used alone. In conclusion, avibactam is able to covalently bind to some bacterial PBPs. Identification of those PBP targets may allow the development of new diazabicyclooctane derivatives with improved affinity for PBPs or new combination therapies that act on multiple PBP targets.
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