Written and Reviewed by Team Pharmacally
AbbVie, a leading company in the biopharmaceutical sector, has announced that the U.S. Food and Drug Administration (FDA) has approved its new antibiotic, Emblaveo (aztreonam and avibactam), for treating complicated intra-abdominal infections (cIAIs) in adults. This approval is a significant step in tackling the increasing global issue of antibiotic resistance. Emblaveo is approved for use alongside metronidazole for patients aged 18 and older who have limited or no alternative treatment options for cIAIs. The Gram-negative bacteria that are susceptible to this treatment include Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Due to the high levels of antimicrobial resistance (AMR) among Gram-negative bacterial infections, healthcare professionals often find it challenging to provide effective treatment. When AMR occurs, the medications designed to combat these infections become ineffective
A Novel Combination Therapy
Emblaveo features a combination of two active ingredients: aztreonam, which is a monobactam antibiotic, and avibactam, a non-β-lactam β-lactamase inhibitor. This combination protects aztreonam from being broken down by serine β-lactamases and helps restore its effectiveness against bacteria that produce both Metallo-β-lactamases (MBLs) and serine β-lactamases. Together, they create a strong mechanism of action that is especially effective against multi-drug-resistant Gram-negative pathogens, including those that produce metallo-β-lactamases (MBLs). These pathogens frequently show resistance to standard antibiotics, making infections challenging to manage.
Metallo-β-lactamases (MBLs) are a type of β-lactamase enzyme that current inhibitors cannot affect, allowing them to break down nearly all β-lactam antibiotics, except for monobactams like aztreonam. Unfortunately, monobactams can still be degraded by other β-lactamases that often occur alongside MBLs, which limits the effectiveness of aztreonam when used alone. However, when aztreonam is combined with avibactam, it can regain its effectiveness against bacteria that produce both MBLs and other β-lactamases, offering a well-tolerated and effective treatment option for multidrug-resistant Gram-negative infections.
Addressing a Critical Need
Complicated intra-abdominal infections (cIAIs) are a major cause of illness and death around the globe. In the United States, about 3.5 million people are impacted each year. These infections can start with issues like appendicitis and can spread beyond one organ, resulting in peritonitis, abscesses, or sepsis. A growing concern is the rise of antibiotic-resistant bacteria, especially Gram-negative strains, which makes treatment more difficult and increases the chances of negative outcomes. Effectively managing cIAIs requires a team approach that includes prompt diagnosis, surgical treatment, and the right antimicrobial medications.
The approval of Emblaveo meets a crucial demand for new treatment options in the face of increasing antibiotic resistance, which is a significant public health concern. The launch of Emblaveo represents a promising step forward in the treatment of cIAIs, equipping healthcare professionals with an effective weapon against difficult infections and aiding in the fight against antimicrobial resistance.
Clinical Trial Result
The FDA has approved Emblaveo based on findings from the comprehensive Phase 3 REVISIT clinical trial, which demonstrated the drug’s safety and effectiveness. This trial was a randomized, active-controlled, central assessor-blinded, multicenter study aimed at assessing the efficacy, safety, and tolerability of Emblaveo (a combination of aztreonam and avibactam) with or without metronidazole, in comparison to meropenem with or without colistin. A total of 422 patients participated in the trial across 81 locations worldwide, specifically targeting individuals with complicated intra-abdominal infections (cIAI) or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP). Out of these, 312 hospitalized patients with cIAI were randomly assigned in a 2:1 ratio to receive either Emblaveo with metronidazole or meropenem with or without colistin, with treatment lasting between five to fourteen days.
The primary endpoint of the study was to achieve clinical cure at the test-of-cure visit within the intent-to-treat (ITT) population. Secondary goals included assessing 28-day mortality and safety in the ITT population that received the study drug. The results showed that Emblaveo, when used alongside metronidazole, was both effective and well-tolerated, with no new safety concerns and a safety profile comparable to that of aztreonam alone. These results indicate that Emblaveo may be a valuable treatment option for patients facing serious infections caused by Gram-negative bacteria, particularly those with limited or no alternative therapies, including multidrug-resistant pathogens that produce metallo-β-lactamase.
Safety Profile of Emblaveo
The safety profile of Emblaveo is generally regarded as acceptable and is comparable to that of aztreonam when administered alone.
Common Side Effects:
Anemia: Seen in roughly 6.9% of patients.
Diarrhea: Reported in about 6.2% of patients.
Elevated Liver Enzymes: Increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed in 6.2% and 5.2% of patients, respectively.
Hypersensitivity Reactions:
Severe hypersensitivity reactions, such as anaphylaxis, have been documented. Emblaveo is not recommended for patients who have a history of severe hypersensitivity to any beta-lactam antibacterial agent. It is important to monitor patients for allergic reactions while undergoing treatment.
Clostridioides difficile-Associated Diarrhea:
Using antibiotics can cause an overgrowth of resistant organisms, such as Clostridioides difficile, which can lead to severe diarrhea. If a patient experiences significant diarrhea, it may be necessary to stop Emblaveo and consider appropriate treatment.
Sodium Content:
Each vial of Emblaveo contains approximately 44.6 mg of sodium. This should be taken into account for patients on sodium-restricted diets.
Use in Specific Populations:
Pregnancy and Lactation: There is limited information regarding the use of Emblaveo in pregnant or breastfeeding women. It should only be used during pregnancy if the potential benefits outweigh the risks to the fetus. A decision should be made about whether to stop breastfeeding or to discontinue the medication, taking into account the importance of the drug for the mother.
Pediatric Use: The safety and effectiveness of Emblaveo in individuals under 18 years of age have not been established.
The Role of Antimicrobial Stewardship and Future Directions
AbbVie highlights the critical role of antimicrobial stewardship in the use of Emblaveo (aztreonam and avibactam), stressing that it should be administered primarily to patients who have few or no alternative treatment options. This focused strategy ensures that Emblaveo is utilized in the most necessary situations, helping to reduce the risk of further antimicrobial resistance. By promoting the careful use of Emblaveo, AbbVie supports global initiatives aimed at tackling antimicrobial resistance, ensuring that this new therapy remains effective for treating complicated intra-abdominal infections caused by multidrug-resistant Gram-negative bacteria. The approval of Emblaveo reflects AbbVie’s dedication to developing innovative solutions for infectious diseases. In addition to complicated intra-abdominal infections, AbbVie is investigating other potential uses and therapeutic applications for this drug combination, which could broaden its impact in the fight against antimicrobial resistance.
Conclusion
The FDA’s approval of Emblaveo highlights the pressing demand for new antibiotics to combat multidrug-resistant infections. As a pioneering treatment for complicated intra-abdominal infections, Emblaveo represents a significant advancement for patients and an essential resource for healthcare providers. AbbVie’s dedication to tackling global health issues remains a key factor in fostering innovation and enhancing patient outcomes around the globe.
References:
1. U.S. FDA Approves EMBLAVEO™ (aztreonam and avibactam) for the Treatment of Adults With Complicated Intra-Abdominal Infections With Limited or No Treatment Options, PRNewswire, 07 Feb 2025-02-12
2. U.S. FDA Approves EMBLAVEO™ (aztreonam and avibactam) for the Treatment of Adults With Complicated Intra-Abdominal Infections With Limited or No Treatment Options, News Centre, Abbvie, 07 Feb 2025
3. Emblaveo (aztreonam/avibactam) – Uses, Side Effects, and More, WebMD, 09 Feb. 2025
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6. Carmeli Y, Cisneros JM, Paul M, et al, Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study. Open Forum Infect Dis. 2023 Nov 27; 10(Suppl 2):ofad500.2476. doi: 10.1093/ofid/ofad500.2476. PMCID: PMC10676936.
7. Carmeli Y, Cisneros JM, Paul M, COMBACTE-CARE consortium et al, REVISIT study group. 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 Feb;25(2):218-230. Doi: 10.1016/S1473-3099(24)00499-7. Epub 2024 Oct 7. PMID: 39389071.
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