ArticleThe Journal of antimicrobial chemotherapy2020
In vitro selection of aztreonam/avibactam resistance in dual-carbapenemase-producing Klebsiella pneumoniae.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Breaking the deadlock of metallo-β-lactamases: evidence and prospects for Aztreonam/Avibactam.Emerging microbes & infections · 2026Review
- Emergence of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae with Penicillin-Binding Protein 3 Insertions, Taiwan, 2021.Emerging infectious diseases · 2026Review
- Ceftazidime/avibactam and aztreonam combined with an aminoglycoside combat metallo-β-lactamase-producingAntimicrobial agents and chemotherapy · 2026Article
- HighMicrobiology spectrum · 2026Article
- Genomic epidemiology and aztreonam-avibactam resistance mechanisms of Proteus mirabilis in china: an eight-year retrospective study.Annals of clinical microbiology and antimicrobials · 2026Article
- Zinc starvation uncovers bacterial host-specific proteases that shape NDM adaptability inmBio · 2026Article
- Evaluation of the in vitro efficacy of antimicrobials against Enterobacterales with multiple carbapenemase enzymes.Iranian journal of microbiology · 2025Article
- Spectrum of cefepime-taniborbactam coverage against 190 β-lactamases defined in engineered isogenicAntimicrobial agents and chemotherapy · 2025Article
- Aztreonam-avibactam: a new combination with activity against multidrug-resistant Klebsiella pneumoniae complex.The Journal of antibiotics · 2025Article
- Molecular resistance mechanisms to newly approved antibiotics (2017-2025) in WHO priority pathogens.Frontiers in microbiology · 2025Review
- Assessment of broth disk elution method for aztreonam in combination with ceftazidime/avibactam againstMicrobiology spectrum · 2024Article
- Practical Application of Aztreonam-Avibactam as a Treatment Strategy for Ambler Class B Metallo-β-Lactamase Producing Enterobacteriaceae.Antibiotics (Basel, Switzerland) · 2024Review
- Article
- Treatment of a challenging NDM and OXA-48-producingIDCases · 2024Article
- An NDM-ProducingOpen forum infectious diseases · 2023Article
- Resistance to aztreonam-avibactam due to a mutation of SHV-12 in Enterobacter.Annals of clinical microbiology and antimicrobials · 2023Article
- Dissemination and characteristics of carbapenem-resistantFrontiers in microbiology · 2023Article
- Development of Resistance to Eravacycline by Klebsiella pneumoniae and Collateral Sensitivity-Guided Design of Combination Therapies.Microbiology spectrum · 2022Article
- In-vitro susceptibility testing methods for the combination of ceftazidime-avibactam with aztreonam in metallobeta-lactamase producing organisms: Role of combination drugs in antibiotic resistance era.The Journal of antibiotics · 2022Article
- Current and Potential Therapeutic Options for Infections Caused by Difficult-to-Treat and Pandrug Resistant Gram-Negative Bacteria in Critically Ill Patients.Antibiotics (Basel, Switzerland) · 2022Review
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Authors and funding
12 authors at 9 institutions in 3 countries.
Funding
Abstract
objectivesTo examine the in vitro selection of aztreonam/avibactam resistance among MBL-producing Klebsiella pneumoniae and to understand the mechanism of increased resistance.
methodsThe MICs of aztreonam were determined with and without avibactam (4 mg/L) using a broth microdilution method. Single-step and multi-step mutant selection was conducted on five MBL-producing K. pneumoniae strains, including two dual carbapenemase producers. Genomic sequencing and gene cloning were performed to investigate the mechanism of increased resistance.
resultsWe examined the MICs for 68 MBL-producing K. pneumoniae isolates, including 13 dual carbapenemase producers. Compared with aztreonam alone, the addition of avibactam (4 mg/L) reduced the MICs for all isolates by >128-fold, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively. One NDM-1-, OXA-48-, CTX-M-15- and CMY-16-positive ST101 K. pneumoniae strain was selected to be resistant to aztreonam/avibactam, with a >16-fold increase in MIC (>128 mg/L). WGS revealed that the resistant mutants lost the blaNDM-1 gene, but acquired amino acid substitutions in CMY-16 (Tyr150Ser and Asn346His). Construction of blaCMY-16 mutants confirmed that the substitutions (Tyr150Ser and Asn346His) were primarily responsible for the decreased susceptibility to aztreonam/avibactam. In addition, transfer of blaCMY-16 mutant (Tyr150Ser and Asn346His) plasmid constructs into certain clinical carbapenemase-producing isolates demonstrated >64-fold increased MICs of aztreonam/avibactam and aztreonam/avibactam/ceftazidime.
conclusionsAztreonam in combination with avibactam showed potent in vitro activity against MBL-producing K. pneumoniae. However, our study suggested the likelihood of aztreonam/avibactam resistance among MBL- and AmpC-co-producing strains and clinical practice should beware of the possibility of the emerging resistance.
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