Related Experiment Video
Updated: Jan 6, 2026
Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Microbiological, Clinical, and Pharmacokinetic/Pharmacodynamic Data to Support EUCAST Aztreonam-Avibactam Minimum
Susan R Raber1,2, Rujia Xie3, Halley Rogers4
1Pfizer Inc., La Jolla, CA, USA. susanraber@gmail.com.
Introduction:
Aztreonam-avibactam was approved for adults with limited treatment options for multiple infections due to aerobic Gram-negative organisms in the European Union and for complicated intra-abdominal infection in the US, following the phase 3 REVISIT and ASSEMBLE trials. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) assigned minimum inhibitory concentration (MIC) breakpoints for aztreonam-avibactam against Enterobacterales of susceptible ≤ 4 mg/l and resistant > 4 mg/l.
Methods:
A comprehensive synthesis of data supporting MIC breakpoint determination is summarized, including: joint probability of pharmacokinetic/pharmacodynamic target attainment (JPTA) analyses (based on population pharmacokinetic modeling) for aztreonam-avibactam dose selection; MIC distributions of target pathogens; clinical and microbiological efficacy outcomes; and exposure-response analyses.
Results:
Among 100,228 Enterobacterales isolates, including 2449 metallo-β-lactamase-positive isolates from global surveillance studies (2017-2021), 99% had aztreonam-avibactam MICs of ≤ 8 mg/l. At MIC = 8 mg/l, the predicted JPTA at steady state was 89% to > 99% across subgroups of varying renal function, based on approved doses for aztreonam-avibactam. Clinical trial isolates fell within the same MIC distribution as surveillance studies. There was no evidence of decreased favorable microbiological responses with increasing aztreonam-avibactam MICs in clinical trials; however, in the clinical dataset, there were few Enterobacterales isolates with aztreonam-avibactam MICs of > 4 mg/l.
Conclusions:
MIC distributions and JPTA simulations supported a susceptible MIC breakpoint for aztreonam-avibactam against Enterobacterales of ≤ 8 mg/l. However, limited clinical outcomes data for Enterobacterales with aztreonam-avibactam MIC ≥ 4 mg/l justified the more conservative breakpoints established by EUCAST.
Clinical Trial Registration:
ClinicalTrials.gov, NCT03329092 and NCT03580044. Studies/analyses sponsored by Pfizer.
More Related Videos
09:07Author Spotlight: Accelerating Diagnostic Accuracy with Direct Identification of Gram-Negatives from Blood Culture Bottles
Published on: May 24, 2024
12:03Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
