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Abstract

Objective:

Aztreonam-avibactam (ATM-AVI) is used for difficult-to-treat gram-negative infections. The objective of this review is to analyze the pharmacology, safety, and clinical application of ATM-AVI.

Data sources:

PubMed, Embase, and ClinicalTrials.gov were searched using the terms aztreonam avibactam, PF-06947387, Emblaveo, and ATM-AVI.

Study selection and data extraction:

Articles written in English and published from January 1, 1985, to June 10, 2025, that related to pharmacology, safety, clinical trials, and clinical application of ATM-AVI were reviewed.

Data synthesis:

The ATM-AVI has shown similar efficacy to comparator antibiotics in complicated intra-abdominal infection (cIAI) and hospital/ventilator-acquired pneumonia (HAP/VAP). The REVISIT trial showed cIAI clinical cure rates of 76.4% and 74% for the ATM-AVI and meropenem groups, respectively (treatment difference 2.4% [95% confidence interval, CI = −7.4 to 13.0]). For HAP/VAP, clinical cure rates were 45.9% and 41.7% for the ATM-AVI and meropenem groups, respectively (treatment difference 4.3% [95% CI = −15.1 to 23.1]). The ATM-AVI was generally well tolerated, with hepatic adverse effects being the most commonly reported.

Relevance to patient care and clinical practice comparison to existing drugs:

The ATM-AVI has demonstrated clinical efficacy for the treatment of cIAI. However, its role needs to be further studied for other infections such as HAP/VAP, urinary tract, and other serious infections. Pharmacoeconomic analysis may be needed to assess the cost-benefit impact in the United States.

Conclusion:

The ATM-AVI may be an alternative option for the treatment of cIAI and other complicated gram-negative infections. Further studies are needed to delineate the role of ATM-AVI in clinical practice.

Keywords

aztreonam-avibactam cIAI Emblaveo

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References

CDC. Antimicrobial resistance threats in the United States, 2021-2022. Antimicrobial resistance. Published February 4, 2025. Accessed March 14, 2025. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/update-2022.html

Hammoudi Halat

Ayoub Moubareck

. The current burden of carbapenemases: review of significant properties and dissemination among gram-negative bacteria. Antibiotics. 2020;9(4):186. doi:10.3390/antibiotics9040186

Tan

Kim

Baugh

, et al Therapeutic options for metallo-beta-lactamase-producing Enterobacterales. Infect Drug Resist. 2021;14:125-142. doi:10.2147/IDR.S246174

AbbVie News Center. U.S. FDA approves EMBLAVEOTM (aztreonam and avibactam) for the treatment of adults with complicated intra-abdominal infections with limited or no treatment options. Accessed March 14, 2025. https://news.abbvie.com/2025-02-07-U-S-FDA-Approves-EMBLAVEO-TM-aztreonam-and-avibactam-for-the-Treatment-of-Adults-With-Complicated-Intra-Abdominal-Infections-With-Limited-or-No-Treatment-Options

Emblaveo (aztreonam and avibactam) [package insert]. AbbVie Inc. Accessed February 10, 2025. https://www.rxabbvie.com/pdf/emblaveo_pi.pdf

Ramsey

MacGowan

AP.

A review of the pharmacokinetics and pharmacodynamics of aztreonam. J Antimicrob Chemother. 2016;71(10):2704-2712. doi:10.1093/jac/dkw231

Lahiri

Johnstone

Ross

McLaughlin

Olivier

Alm

RA.

Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance. Antimicrob Agents Chemother. 2014;58(10):5704-5713. doi:10.1128/aac.03057-14

Pfizer. A Phase I, Single Center, Open-Label Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam Administered as Single and Repeated Intravenous Doses in Healthy Chinese Participants. ClinicalTrials.gov; 2022. Accessed May 15, 2025. https://clinicaltrials.gov/study/NCT04973826

Lodise

O’Donnell

Balevic

, et al Pharmacokinetics of ceftazidime-avibactam in combination with aztreonam (COMBINE) in a phase 1, open-label study of healthy adults. Antimicrob Agents Chemother. 2022;66(12):e0093622. doi:10.1128/aac.00936-22

10.

van den Berg

. 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). ClinicalTrials.gov; 2017. Accessed May 15, 2025. https://clinicaltrials.gov/study/NCT01689207

11.

Pfizer. An Open-Label, Parallel-Group, Pharmacokinetic Study of Multiple Intravenous Doses of Aztreonam and Avibactam in Subjects With Severe Renal Impairment and Normal Renal Function. ClinicalTrials.gov; 2022. Accessed May 15, 2025. https://clinicaltrials.gov/study/NCT04486625

12.

Cornely

Cisneros

Torre-Cisneros

, et al Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study. J Antimicrob Chemother. 2020;75(3):618-627. doi:10.1093/jac/dkz497

13.

European Medicines Agency. Emblaveo. Published 2024. Accessed June 5, 2025. https://www.ema.europa.eu/en/documents/product-information/emblaveo-epar-product-information_en.pdf

14.

Carmeli

Cisneros

Paul

, et al Aztreonam–avibactam versus meropenem for the treatment of serious infections caused by Gram-negative bacteria (REVISIT): a descriptive, multinational, open-label, phase 3, randomised trial. Lancet Infect Dis. 2025;25(2):218-230. doi:10.1016/S1473-3099(24)00499-7

15.

Pfizer. A Phase 2A, 2-Part, Open-Label, Non-Randomized, Multicenter, Single and Multiple Dose Trial to Evaluate Pharmacokinetics, Safety and Tolerability of Aztreonam and Avibactam ± Metronidazole in Neonates and Infants From Birth to Less Than 9 Months of Age With Suspected or Confirmed Infections Due to Gram-Negative Pathogens Requiring Intravenous Antibiotic Treatment. ClinicalTrials.gov; 2025. Accessed June 1, 2025. https://clinicaltrials.gov/study/NCT06462235

16.

Pfizer. A Phase 2A Multicenter, Observer-Blinded, Randomized 2 Arm Study to Investigate Pharmacokinetics, Safety, Tolerability and Efficacy of Intravenous Aztreonam-Avibactam ± Metronidazole Compared to Best Available Therapy (Bat) in Pediatric Participants 9 Months to Less Than 18 Years of Age With Serious Gram-Negative Bacterial Infections Including Complicated Intra-Abdominal Infection. ClinicalTrials.gov; 2025. Accessed June 1, 2025. https://clinicaltrials.gov/study/NCT05639647

17.

Tamma

Heil

Justo

Mathers

Satlin

Bonomo

. Infectious Diseases Society of America 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections [published online ahead of print August 7, 2024]. Clin Infect Dis. doi:10.1093/cid/ciae403

18.

Bao

Woodcock

Virgilio

Kantecki

Chow

Gheorghe

EE34 cost-effectiveness analysis of aztreonam-avibactam (ATM-AVI) versus meropenem for the treatment of serious infections due to gram-negative bacteria for which there are limited treatment options (LTO) in Italy. Value Health. 2023;26(12):S56. doi:10.1016/j.jval.2023.09.307

The Combination of Aztreonam-Avibactam in Multidrug-Resistant Gram-Negative Infections