ArticleThe Journal of antimicrobial chemotherapy2015
Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 133 citations in OpenAlex.
- Repeated insertions at positions 261-280 in KPC-2 highlight a ceftazidime-avibactam resistance hotspot.iScience · 2026Article
- Reduced catalytic activity of KPC β-lactamase can increase ceftazidime resistance.Communications biology · 2026Article
- Heterogeneous multicopy of blaNature communications · 2026Article
- Genomic characterization of ceftazidime/avibactam-resistantFrontiers in microbiology · 2026Article
- Emergence of ceftazidime-avibactam resistance in clinical Klebsiella pneumoniae during therapy.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Article
- Impact of the double deletion ΔG242-T243 in KPC-2 in the effectiveness of ceftazidime-avibactam and imipenem-relebactam.Antimicrobial agents and chemotherapy · 2025Article
- Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms.Archives of microbiology · 2025Review
- [In vitro activity of ceftazidime- avibactam and ceftolozane- tazobactam against clinical isolates of enterobacteriaceae andAnnals of burns and fire disasters · 2025Article
- Global phylogeography and genetic characterization of carbapenem and ceftazidime-avibactam resistant KPC-33-producing Pseudomonas aeruginosa.npj antimicrobials and resistance · 2025Article
- Evolution of ceftazidime-avibactam resistance driven by variation inFrontiers in cellular and infection microbiology · 2025Article
- Molecular mechanisms responsible KPC-135-mediated resistance to ceftazidime-avibactam in ST11-K47 hypervirulentEmerging microbes & infections · 2024Article
- In vitro mimicry of in vivo KPC mutations by ceftazidime-avibactam: phenotypes, mechanisms, genetic structure and kinetics of enzymatic hydrolysis.Emerging microbes & infections · 2024Article
- Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms ofEmerging microbes & infections · 2024Article
- Article
- The role of early use of Carbapenems perioperatively for urolithiasis with ESBL-producing Escherichia coli.BMC urology · 2024Article
- Rapid Detection of Ceftazidime/Avibactam Susceptibility/Resistance in Enterobacterales by Rapid CAZ/AVI NP Test.Emerging infectious diseases · 2024Article
- TheAntibiotics (Basel, Switzerland) · 2023Article
- In Vitro Evaluation of Increasing Avibactam Concentrations on Ceftazidime Activity against Ceftazidime/Avibactam-Susceptible and Resistant KPC-ProducingAntibiotics (Basel, Switzerland) · 2023Article
- Exploring avibactam and relebactam inhibition ofAntimicrobial agents and chemotherapy · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesThe objective of this study was to explore the activity of ceftazidime and ceftazidime/avibactam against a collection of isogenic strains of Escherichia coli DH10B possessing SHV and KPC β-lactamases containing single amino acid substitutions in the Ω-loop (residues 164-179).
methodsCeftazidime and ceftazidime/avibactam MICs were determined by the agar dilution method for a panel of isogenic E. coli strains expressing SHV-1 and KPC-2 with amino acid substitutions at positions 164, 167, 169 or 179. Two KPC-2 β-lactamase variants that possessed elevated MICs of ceftazidime/avibactam were selected for further biochemical analyses.
resultsAvibactam restored susceptibility to ceftazidime for all Ω-loop variants of SHV-1 with MICs <8 mg/L. In contrast, several of the Arg164 and Asp179 variants of KPC-2 demonstrated MICs of ceftazidime/avibactam >8 mg/L. β-Lactamase kinetics showed that the Asp179Asn variant of KPC-2 demonstrated enhanced kinetic properties against ceftazidime. The Ki app, k2/K and koff of the Arg164Ala and Asp179Asn variant KPC-2 β-lactamases indicated that avibactam effectively inhibited these enzymes.
conclusionsSeveral KPC-2 variants demonstrating ceftazidime resistance as a result of single amino acid substitutions in the Ω-loop were not susceptible to ceftazidime/avibactam (MICs >8 mg/L). We hypothesize that this observation is due to the stabilizing interactions (e.g. hydrogen bonds) of ceftazidime within the active site of variant β-lactamases that prevent avibactam from binding to and inhibiting the β-lactamase. As ceftazidime/avibactam is introduced into the clinic, monitoring for new KPC-2 variants that may exhibit increased ceftazidime kinetics as well as resistance to this novel antibiotic combination will be important.
Indexed as
Identifiers
What OpenQuestion holds
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.