ArticleThe Journal of antimicrobial chemotherapy2020
Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model.
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 54 papers.
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Who cites it
54 citing papers in PubMed, 73 citations in OpenAlex.
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Evaluating the efficacy of ceftazidime/avibactam plus amikacin combination therapy as a carbapenem-sparing agent against ceftazidime/avibactam-resistantAntimicrobial agents and chemotherapy · 2026Article
- Determining the Activity of Imipenem/Relebactam Plus Aztreonam Against ConstitutiveOpen forum infectious diseases · 2026Article
- Co-Administration Dosing of Ceftazidime-Avibactam and Aztreonam in Patients with Varying Renal Function for Carbapenem-Resistant Enterobacterales Infections via Monte Carlo Simulation.Infection & chemotherapy · 2026Article
- Physical compatibility of ceftazidime-avibactam with selected intravenous antimicrobials in simulated Y-site administration.European journal of hospital pharmacy : science and practice · 2026Article
- Continuous Infusion of Aztreonam-Avibactam After High Loading Dose for an Infection Caused by an OXA-48- and NDM-1-Co-producing ST147 Klebsiella pneumoniae.Infectious diseases and therapy · 2026Article
- Preventing resistance development in infections by OXA β-lactamase-producing Pseudomonas aeruginosa: correlating clinical outcomes with hollow-fibre model input.The Journal of antimicrobial chemotherapy · 2026Article
- Combination Therapy with Ceftazidime-Avibactam, Aztreonam, and Topical Polymyxin B for NDM-ProducingInfection and drug resistance · 2026Article
- Aztreonam-Avibactam Successfully Treated SevereJournal of blood medicine · 2026Article
- Newer antibiotics for drug-resistant Gram-negative infections in immunocompromised hosts: from pivotal trials to high-risk practice.Frontiers in cellular and infection microbiology · 2026Review
- Combatting mobile colistin-resistant (MCR), metallo-β-lactamase (MBL)-producingJAC-antimicrobial resistance · 2025Article
- Pharmacodynamic Evaluation of Adjuvant Targets: Low Molecular Weight PBP7/8 Effects on β-Lactam Activity Against Carbapenem-Resistant Acinetobacter Baumannii.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pharmacodynamics of aztreonam/ceftazidime/avibactam and polymyxin B versus New Delhi MBL-producing Acinetobacter baumannii.JAC-antimicrobial resistance · 2025Article
- In vitro activity and resistance mechanisms of novel antimicrobial agents against metallo-β-lactamase producers.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Review
- A Comprehensive Overview of Antibacterial Agents for Combating Multidrug-Resistant Bacteria: The Current Landscape, Development, Future Opportunities, and Challenges.Antibiotics (Basel, Switzerland) · 2025Review
- Therapeutic challenges in managingFrontiers in cellular and infection microbiology · 2025Review
- Carbapenem-ResistantCase reports in infectious diseases · 2025Article
- DynamicAntibiotics (Basel, Switzerland) · 2024Review
- Rationale and Logistics of Continuous Infusion Cephalosporin Antibiotics.Pharmacy (Basel, Switzerland) · 2024Review
- Aztreonam-avibactam: The dynamic duo against multidrug-resistant gram-negative pathogens.Pharmacotherapy · 2024Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundMBL-producing strains of Enterobacteriaceae are a major public health concern. We sought to define optimal combination regimens of ceftazidime/avibactam with aztreonam in a hollow-fibre infection model (HFIM) of MBL-producing strains of Escherichia coli and Klebsiella pneumoniae.
methodsE. coli ARLG-1013 (blaNDM-1, blaCTX-M, blaCMY, blaTEM) and K. pneumoniae ARLG-1002 (blaNDM-1, blaCTXM-15, blaDHA, blaSHV, blaTEM) were studied in the HFIM using simulated human dosing regimens of ceftazidime/avibactam and aztreonam. Experiments were designed to evaluate the effect of staggered versus simultaneous administration, infusion duration and aztreonam daily dose (6 g/day versus 8 g/day) on bacterial killing and resistance suppression. Prospective validation experiments for the most active combination regimens were performed in triplicate to ensure reproducibility.
resultsStaggered administration of the combination (ceftazidime/avibactam followed by aztreonam) was found to be inferior to simultaneous administration. Longer infusion durations (2 h and continuous infusion) also resulted in enhanced bacterial killing relative to 30 min infusions. The rate of killing was more pronounced with 8 g/day versus 6 g/day aztreonam combination regimens for both tested strains. In the prospective validation experiments, ceftazidime/avibactam with aztreonam dosed every 8 and 6 h, respectively (ceftazidime/avibactam 2/0.5 g every 8 h + aztreonam 2 g every 6 h), or ceftazidime/avibactam with aztreonam as continuous infusions resulted in maximal bacterial killing and resistance suppression over 7 days.
conclusionsSimultaneous administration of aztreonam 8 g/day given as a continuous or 2 h infusion with ceftazidime/avibactam resulted in complete bacterial eradication and resistance suppression. Further study of this combination is needed with additional MBL-producing Gram-negative pathogens. The safety of this double β-lactam strategy also warrants further study in Phase 1 clinical trials.
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