ArticleAntimicrobial agents and chemotherapy2013
Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 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
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Trial
- NMR crystallography reveals active-site protonation states of Toho-1 β-lactamase in complex with avibactam.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Zwitterionic Penicillin-Derived Sulfone Inhibitor for Combating β-Lactamase-Mediated Antibiotic Resistance.ChemMedChem · 2026Article
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- Article
- Structural perspectives on clinical β-lactamase inhibitors: From mechanism to resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics.Pharmaceuticals (Basel, Switzerland) · 2026Review
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- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Backbone assignment of a 28.5 kDa class A extended spectrum β-lactamase by high-field, carbon-detected solid-state NMR.Biomolecular NMR assignments · 2025Article
- Ω-Loop mutations control dynamics of the active site by modulating the hydrogen-bonding network in PDC-3 β-lactamase.bioRxiv : the preprint server for biology · 2025Article
- Article
- Functional and structural analyses of amino acid sequence variation in PDC β-lactamase reveal different mechanistic pathways toward cefiderocol resistance inAntimicrobial agents and chemotherapy · 2025Article
- Structure and mechanism of taniborbactam inhibition of the cefepime-hydrolyzing, partial R2-loop deletionAntimicrobial agents and chemotherapy · 2025Article
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- β-Lactamase diversity inAntimicrobial agents and chemotherapy · 2025Article
- Revitalizing cephalosporins: The promise of β-lactamase inhibitor combinations.GMS hygiene and infection control · 2025Article
- Study on the invitro synergistic susceptibility and biofilm inhibition mechanism of ceftazidime-avibactam combined with aztreonam against carbapenem-resistantFrontiers in microbiology · 2025Article
- Crystal structure of the class A extended-spectrum β-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution.Antimicrobial agents and chemotherapy · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although β-lactams have been the most effective class of antibacterial agents used in clinical practice for the past half century, their effectiveness on Gram-negative bacteria has been eroded due to the emergence and spread of β-lactamase enzymes that are not affected by currently marketed β-lactam/β-lactamase inhibitor combinations. Avibactam is a novel, covalent, non-β-lactam β-lactamase inhibitor presently in clinical development in combination with either ceftaroline or ceftazidime. In vitro studies show that avibactam may restore the broad-spectrum activity of cephalosporins against class A, class C, and some class D β-lactamases. Here we describe the structures of two clinically important β-lactamase enzymes bound to avibactam, the class A CTX-M-15 extended-spectrum β-lactamase and the class C Pseudomonas aeruginosa AmpC β-lactamase, which together provide insight into the binding modes for the respective enzyme classes. The structures reveal similar binding modes in both enzymes and thus provide a rationale for the broad-spectrum inhibitory activity of avibactam. Identification of the key residues surrounding the binding pocket allows for a better understanding of the potency of this scaffold. Finally, avibactam has recently been shown to be a reversible inhibitor, and the structures provide insights into the mechanism of avibactam recyclization. Analysis of the ultra-high-resolution CTX-M-15 structure suggests how the deacylation mechanism favors recyclization over hydrolysis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.