ArticleCPT: pharmacometrics & systems pharmacology2019
Semimechanistic Pharmacodynamic Modeling of Aztreonam-Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug-Resistant Gram-Negative Bacteria.
Article in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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
6 citing papers in PubMed, 11 citations in OpenAlex.
- In vitro activity of ceftazidime-avibactam/aztreonam combination against MBL-producing Pseudomonas aeruginosa strains.Infection · 2025Article
- Revisiting the Checkerboard to Inform Development of β-Lactam/β-Lactamase Inhibitor Combinations.Antibiotics (Basel, Switzerland) · 2024Article
- Transient comparison of techniques to counter multi-drug resistant bacteria: prime modules in curation of bacterial infections.Frontiers in antibiotics · 2023Review
- Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools.Open forum infectious diseases · 2022Review
- The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials.Pharmaceutics · 2021Review
- Metallo-ß-lactamases: a review.Molecular biology reports · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aztreonam-avibactam (ATM-AVI) is a promising combination to treat serious infections caused by multidrug-resistant (MDR) pathogens. Three distinct mechanisms of action have been previously characterized for AVI: inhibition of ATM degradation by β-lactamases, proper bactericidal effect, and enhancement of ATM bactericidal activity. The aim of this study was to quantify the individual contribution of each of the three AVI effects. In vitro static time-kill studies were performed on four MDR Enterobacteriaceae with different β-lactamase profiles. β-Lactamase activity was characterized by measuring ATM concentrations over 27 hours. Data were analyzed by a semimechanistic pharmacodynamics modeling approach. Surprisingly, even though AVI prevented ATM degradation, the combined bactericidal activity was mostly explained by the enhancement of ATM effect within clinical range of ATM (5-125 mg/L) and AVI concentrations (0.9-22.5 mg/L). Therefore, when selecting a β-lactamase inhibitor for combination with a β-lactam, its capability to enhance the β-lactam activity should be considered in addition to the spectrum of β-lactamases inhibited.
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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.