Trial reportEuropean journal of clinical pharmacology2024
Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation.
Trial report in European journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 19 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.
The trial behind it
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.
A Phase I, Randomised, Double-blind, 3-Part Study in Healthy Young and Elderly Subjects to Assess the Safety and Tolerability, and Investigate the Pharmacokinetics of Aztreonam and Avibactam Given Alone and in Combination (ATM-AVI)
A phase iia prospective, open-label, multicenter study to determine the pharmacokinetics (pk) and safety and tolerability of aztreonam-avibactam (atm-avi) for the treatment of complicated intra-abdominal infections (ciais) in hospitalized adults
A phase 3 prospective, randomized, multicenter, open-label, central assessor-blinded, parallel group, comparative study to determine the efficacy, safety and tolerability of aztreonam-avibactam (atm-avi) ±metronidazole (mtz) versus meropenem±colistin (mer±col) for the treatment of serious infections due to gram negative bacteria, including metallo-β-lactamase (mbl) - producing multidrug resistant pathogens, for which there are limited or no treatment options
A prospective, randomized,open-label, comparative study to assess the efficacy, safety and tolerability of aztreonam- avibactam (atm-avi) and best available therapy for the treatment of serious infections due to multi-drug resistant gram- negative bacteria producing metallo -β-lactamase (mbl)
Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Dose Selection for Ceftibuten Combined with Avibactam Tomilopil, a Potential Oral Alternative to Carbapenems for Patients with Complicated Urinary Tract Infections.Journal of clinical pharmacology · 2026Trial
- Population pharmacokinetic/pharmacodynamic modeling to optimize aztreonam-avibactam dose regimens for adult patients.Antimicrobial agents and chemotherapy · 2025Trial
- Article
- Aztreonam-avibactam at the frontline: A dual-agent approach to metallo-β-lactamase resistance.The Journal of antibiotics · 2026Review
- Dosing Regimen Optimization of Aztreonam/Avibactam According to Renal Function Stratification: A Population Pharmacokinetic-Guided Simulation Study.Antibiotics (Basel, Switzerland) · 2026Article
- Accurate and Sensitive UHPLC-Tandem Mass Spectrometry Sequential Methods for Therapeutic Drug Monitoring of Aztreonam/Avibactam in Human Plasma.Pharmaceutics · 2026Article
- Pharmacokinetics of Aztreonam-Avibactam After Single- and Multiple-Dose Administration: A Phase 1, Open-Label Study in Healthy Chinese Participants and Ethnic Comparison with Non-Chinese Participants.Clinical pharmacology in drug development · 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
- Microbiological, Clinical, and Pharmacokinetic/Pharmacodynamic Data to Support EUCAST Aztreonam-Avibactam Minimum Inhibitory Concentration Susceptibility Breakpoints Against Enterobacterales.Infectious diseases and therapy · 2026Article
- Cost-Effectiveness Analysis of Aztreonam-Avibactam (ATM-AVI) Versus Colistin + Meropenem (COL + MER) for the Treatment of Infections Caused by Metallo-β-Lactamase (MBL)-Producing Enterobacterales in Italy.PharmacoEconomics · 2025Article
- Use of Aztreonam-Avibactam with Rapid Eravacycline Step-Down Therapy for a Tibial Septic Non-Union by NDM-ProducingAntibiotics (Basel, Switzerland) · 2025Article
- β-Lactam/β-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy.Antibiotics (Basel, Switzerland) · 2025Review
- Mortality of metallo-β-lactamase-producing Enterobacterales bacteremias with combined ceftazidime-avibactam plus aztreonam vs. other active antibiotics: a multicenter target trial emulation.Lancet regional health. Americas · 2025Article
- Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis.The Journal of antimicrobial chemotherapy · 2025Article
- Aztreonam-avibactam: The dynamic duo against multidrug-resistant gram-negative pathogens.Pharmacotherapy · 2024Review
- Review
- First Clinical Application of Aztreonam-Avibactam in Treating Carbapenem-Resistant Enterobacterales: Insights from Therapeutic Drug Monitoring and Pharmacokinetic Simulations.Journal of personalized medicine · 2024Article
- The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- Practical Application of Aztreonam-Avibactam as a Treatment Strategy for Ambler Class B Metallo-β-Lactamase Producing Enterobacteriaceae.Antibiotics (Basel, Switzerland) · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeA series of iterative population pharmacokinetic (PK) modeling and probability of target attainment (PTA) analyses based on emerging data supported dose selection for aztreonam-avibactam, an investigational combination antibiotic for serious Gram-negative bacterial infections.
methodsTwo iterations of PK models built from avibactam data in infected patients and aztreonam data in healthy subjects with "patient-like" assumptions were used in joint PTA analyses (primary target: aztreonam 60% fT > 8 mg/L, avibactam 50% fT > 2.5 mg/L) exploring patient variability, infusion durations, and adjustments for moderate (estimated creatinine clearance [CrCL] > 30 to ≤ 50 mL/min) and severe renal impairment (> 15 to ≤ 30 mL/min). Achievement of > 90% joint PTA and the impact of differential renal clearance were considerations in dose selection.
resultsIteration 1 simulations for Phase I/IIa dose selection/modification demonstrated that 3-h and continuous infusions provide comparable PTA; avibactam dose drives joint PTA within clinically relevant exposure targets; and loading doses support more rapid joint target attainment. An aztreonam/avibactam 500/137 mg 30-min loading dose and 1500/410 mg 3-h maintenance infusions q6h were selected for further evaluation. Iteration 2 simulations using expanded PK models supported an alteration to the regimen (500/167 mg loading; 1500/500 mg q6h maintenance 3-h infusions for CrCL > 50 mL/min) and selection of doses for renal impairment for Phase IIa/III clinical studies.
conclusionA loading dose plus 3-h maintenance infusions of aztreonam-avibactam in a 3:1 fixed ratio q6h optimizes joint PTA. These analyses supported dose selection for the aztreonam-avibactam Phase III clinical program. CLINICAL
trial registrationNCT01689207; NCT02655419; NCT03329092; NCT03580044.
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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.