ArticleAntimicrobial agents and chemotherapy2014
Reclaiming the efficacy of β-lactam-β-lactamase inhibitor combinations: avibactam restores the susceptibility of CMY-2-producing Escherichia coli to ceftazidime.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- Pathogenome and Plasmid-Borne Antimicrobial Resistance Phenotypes in a Multidrug-Resistant O111:H8 Shiga Toxin-ProducingbioRxiv : the preprint server for biology · 2026Article
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- Multicenter evaluation of activity of aztreonam in combination with avibactam, relebactam, and vaborbactam against metallo-β-lactamase-producing carbapenem-resistant gram-negative bacilli.Antimicrobial agents and chemotherapy · 2024Article
- Article
- The Effectiveness of Imipenem-Relebactam against Ceftazidime-Avibactam Resistant Variants of the KPC-2 β-Lactamase.Antibiotics (Basel, Switzerland) · 2023Article
- Class C β-Lactamases: Molecular Characteristics.Clinical microbiology reviews · 2022Review
- The Class A β-Lactamase Produced byAntibiotics (Basel, Switzerland) · 2022Article
- Activity of Imipenem-Relebactam against Multidrug- and Extensively Drug-Resistant Burkholderia cepacia Complex and Burkholderia gladioli.Antimicrobial agents and chemotherapy · 2021Article
- Inhibition of theACS infectious diseases · 2021Article
- Structural and Biochemical Characterization of the Novel CTX-M-151 Extended-Spectrum β-Lactamase and Its Inhibition by Avibactam.Antimicrobial agents and chemotherapy · 2021Article
- Article
- Molecular Basis of Class A β-Lactamase Inhibition by Relebactam.Antimicrobial agents and chemotherapy · 2019Article
- Nacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPC.Antimicrobial agents and chemotherapy · 2019Article
- Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent β-Lactam-β-Lactamase Inhibitor Combination.Antimicrobial agents and chemotherapy · 2019Article
- Targeting Multidrug-ResistantmBio · 2019Article
- Relebactam Is a Potent Inhibitor of the KPC-2 β-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae.Antimicrobial agents and chemotherapy · 2018Article
- Defining Substrate Specificity in the CTX-M Family: the Role of Asp240 in Ceftazidime Hydrolysis.Antimicrobial agents and chemotherapy · 2018Article
- Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam.Antimicrobial agents and chemotherapy · 2018Article
- Activity of the β-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
CMY-2 is a plasmid-encoded Ambler class C cephalosporinase that is widely disseminated in Enterobacteriaceae and is responsible for expanded-spectrum cephalosporin resistance. As a result of resistance to both ceftazidime and β-lactamase inhibitors in strains carrying blaCMY, novel β-lactam-β-lactamase inhibitor combinations are sought to combat this significant threat to β-lactam therapy. Avibactam is a bridged diazabicyclo [3.2.1]octanone non-β-lactam β-lactamase inhibitor in clinical development that reversibly inactivates serine β-lactamases. To define the spectrum of activity of ceftazidime-avibactam, we tested the susceptibilities of Escherichia coli clinical isolates that carry bla(CMY-2) or bla(CMY-69) and investigated the inactivation kinetics of CMY-2. Our analysis showed that CMY-2-containing clinical isolates of E. coli were highly susceptible to ceftazidime-avibactam (MIC(90), ≤ 0.5 mg/liter); in comparison, ceftazidime had a MIC90 of >128 mg/liter. More importantly, avibactam was an extremely potent inhibitor of CMY-2 β-lactamase, as demonstrated by a second-order onset of acylation rate constant (k2/K) of (4.9 ± 0.5) × 10(4) M(-1) s(-1) and the off-rate constant (k(off)) of (3.7 ± 0.4) × 10(-4) s(-1). Analysis of the reaction of avibactam with CMY-2 using mass spectrometry to capture reaction intermediates revealed that the CMY-2-avibactam acyl-enzyme complex was stable for as long as 24 h. Molecular modeling studies raise the hypothesis that a series of successive hydrogen-bonding interactions occur as avibactam proceeds through the reaction coordinate with CMY-2 (e.g., T316, G317, S318, T319, S343, N346, and R349). Our findings support the microbiological and biochemical efficacy of ceftazidime-avibactam against E. coli containing plasmid-borne CMY-2 and CMY-69.
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