ArticleThe Journal of antimicrobial chemotherapy2021
Investigation of mechanisms responsible for decreased susceptibility of aztreonam/avibactam activity in clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Clinical Emergence and Genomic Characterization of Aztreonam-Avibactam-ResistantAntibiotics (Basel, Switzerland) · 2026Article
- In vitro activity of aztreonam/avibactam and comparators against Enterobacterales isolates from patients with hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated intra-abdominal infections (ATLAS, 2021-2022).The Journal of antimicrobial chemotherapy · 2026Article
- Emergence of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae with Penicillin-Binding Protein 3 Insertions, Taiwan, 2021.Emerging infectious diseases · 2026Review
- Case Commentary: When one target is not enough-PBP3 insertions and target redundancy inAntimicrobial agents and chemotherapy · 2026Article
- Aztreonam plus ceftazidime/avibactam broth disk elution test: failure to detect Escherichia coli with PBP-3 insertions.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy.Antibiotics (Basel, Switzerland) · 2026Review
- Impact of Susceptibility Testing Methodology on the Positioning of Cefiderocol and Aztreonam-Avibactam Against Metallo-β-Lactamase-Producing Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2026Article
- Synergistic effects of ceftriaxone combined with BLI-489 against NDM-producingMicrobiology spectrum · 2026Article
- Article
- Novel Insights into Carbapenem Resistance: Mechanisms, Diagnostics, and Future Directions.Antibiotics (Basel, Switzerland) · 2026Review
- Review
- Whole-genome analysis of NDM-producingEmerging microbes & infections · 2025Article
- Classification and applicability of new beta-lactamase inhibitors.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2025Review
- Article
- Activity of β-Lactamase Inhibitor Combinations Against Enterobacterales Isolated from Patients with Intra-Abdominal Infection from United States Medical Centres (2019-2023).Antibiotics (Basel, Switzerland) · 2025Article
- Phage-antibiotic synergy to combat multidrug resistant strains of Gram-negative ESKAPE pathogens.Scientific reports · 2025Article
- Evaluation of two gradient diffusion tests to determine susceptibility to aztreonam and ceftazidime-avibactam in combination.Antimicrobial agents and chemotherapy · 2025Article
- From genomics to treatment: overcoming pan-drug-resistantFrontiers in pharmacology · 2025Article
- Molecular resistance mechanisms to newly approved antibiotics (2017-2025) in WHO priority pathogens.Frontiers in microbiology · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe combination aztreonam/avibactam is currently under Phase 3 trials for the treatment of serious infections caused by Gram-negative bacteria including those with MBLs.
objectivesTo investigate the resistance mechanisms in Enterobacterales exhibiting aztreonam/avibactam MICs of ≥4 mg/L.
methodsAmong 8787 Enterobacterales, 17 (0.2%) isolates exhibited an aztreonam/avibactam MIC of ≥4 mg/L. Isolates were sequenced and screened for β-lactamases. Sequences of porins, penicillin-binding protein 3 (PBP3) and expression levels of AmpC and AcrA were evaluated.
resultsEleven (11/4154 isolates; 0.26%) Escherichia coli, three (3/1981; 0.15%) Klebsiella pneumoniae and three (3/628; 0.5%) Enterobacter cloacae were identified. All E. coli showed either an 'YRIK' or 'YRIN' insertion in PBP3. In general, these isolates carried blaCMY and/or blaCTX-M variants, except for one isolate from Korea that also produced NDM-5 and one isolate from Turkey that produced OXA-48. Two DHA-1-producing K. pneumoniae overexpressed acrA and had a premature stop codon in either OmpK35 or OmpK36, whereas a third K. pneumoniae carried blaPER-2 and had a premature stop codon in OmpK35. All three E. cloacae expressed AmpC at levels ≥570-fold, but sequence analysis did not reveal known amino acid alterations associated with decreased avibactam binding or increased hydrolysis of β-lactams. Minor amino acid polymorphisms within OmpC, OmpF and PBP3 were noted among the E. cloacae.
conclusionsA small number of isolates (0.2%) met the inclusion criteria. E. coli showed altered PBP3 as the most relevant resistance mechanism, whereas K. pneumoniae had multiple resistance mechanisms. Further investigations are needed to clarify resistance in E. cloacae.
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