By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration (FDA) has approved a new combination antibiotic for the treatment of complicated intra-abdominal infections (cIAIs) where there are limited or no alternative options. This new antibiotic combines the monobactam, aztreonam, and the synthetic non-β- lactam β-lactamase inhibitor, avibactam. It will be distributed by AbbVie Inc. as Emblaveo and was developed via the FDA’s Qualified Infectious Disease Product pathway.
Indications
Combination aztreonam and avibactam (ATM-AVI), along with metronidazole, is indicated in adult patients (≥ 18 years of age) who have limited or no alternative options for the treatment of cIAIs, including those caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobactor cloacae complex, Citrobacter freundii complex, and Serratia marcensens.1
Dosage
The recommended dose in adults is based on estimated creatinine clearance (CLcr) calculated using the Cockcroft-Gault formula.1 For patients with CLcr > 50 mL/min, the loading dose is 2 g of ATM and 0.67 g of AVI, followed by 1.5 g ATM and 0.5 g of AVI every six hours. The infusion time is three hours. Metronidazole is administered concurrently. The recommended duration of treatment is five to 14 days. ATM-AVI is available in a single-dose vial containing 1.5 g of ATM and 0.5 g of AVI.
Potential Advantages
ATM-AVI has potent in vitro activity against metallo-β-lactamases Ambler Class A, Class C, and some Class D β-lactamases. AVI is highly effective in providing protection to β-lactam antibiotics against hydrolysis caused by chromosomal and plasmid β-lactamases.
Potential Disadvantages
The most frequently reported adverse reactions (> 10%) include hepatic adverse reactions (increase in alanine transaminase, aspartate aminotransferase [hypertransaminasemia]).1 Other adverse reactions (> 5%) include anemia, diarrhea, phlebitis, flushing, rash, nausea, vomiting, and mental status change. Hypersensitivity reactions, serious skin disorders, and Clostridioides difficile infection have been reported.1 ATM-AVI has modest activity against Pseudomonas aeruginosa and does not inhibit class B and some class D β-lactamases.1 It is not active against gram-positive and anaerobic microorganisms. Concomitant use of an organic anion transporter (OAT) 1 or OAT 3 transporter inhibitors with AMT-AVI is not recommended.1
Comments
The efficacy of AMT-AVI was based on in vitro, animal data, and one randomized, active-controlled study in participants with cIAI.1,2 Participants were randomized to AMT-AVI with metronidazole (n = 208) or meropenem (1,000 mg every eight hours) with or without colistin.1,2 Treatment duration was five to 14 days. Optional vancomycin, linezolid, or daptomycin was permitted for gram-positive coverage.
The primary cIAI diagnoses were appendiceal perforation or peri-appendiceal abscess (47% to 51%) followed by cholecystitis-gangrenous rupture or progression beyond gallbladder wall (14% to 18%). The mean participant age was 51 years, 49% of participants were white, and 78% of participants had an Acute Physiology, Age, and Chronic Health Evaluation II score ≤ 10. The most common baseline pathogens were Enterobacterales (96%), with 78% being E. coli. The primary efficacy endpoint was the adjudicated clinical care rate at the test-of-cure visit (within three days either side of day 28). The success rates were 76.4% for AMT-AVI vs. 74.0% for meropenem. However, the trial was not designed with any formal hypotheses for inferential testing against the active comparator.1
Clinical Implications
Because of increasing resistance patterns and poor outcomes of inadequately treated cIAI, new β-lactam/β-lactamase combinations have been developed.3 These include ceftazidime-avibactam, ceftolozone-tazobactam, meropenem-vaborbactam, and imipenem-cilastatin-relevactam with AMI-AVI, the latest addition. While numerous antimicrobial options exist for cIAI, a systematic review and network meta-analysis (45 studies and 14,267 adults) suggests cefepime plus metronidazole as optimal in terms of efficacy, all-cause mortality, and safety.4 AMT-AVI provides another treatment option for cIAI and is estimated to be available in the third quarter of 2025.
References
- AbbVie Inc. Emblaveo prescribing information. Revised February 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217906Orig1s000lbl.pdf
- Carmeli Y, Cisneros JM, Paul M, 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 Infectious Dis. 2025;25(2):218-230.
- Delp H, Gibson GA, Buckman SA. Aztreonam-avibactam for the treatment of intra-abdominal infections. Expert Opin Pharmacother. 2024;25(14):1867-1872.
- Kong W, Deng T, Li S, et al. Efficacy, safety, and tolerability of antimicrobial agents for complicated intra-abdominal infection: A systematic review and network meta-analysis. BMC Infect Dis. 2023;23:256-269.
The U.S. Food and Drug Administration has approved a new combination antibiotic for the treatment of complicated intra-abdominal infections where there are limited or no alternative options.
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