Version July 2025
Dosing guidance:
Dosing: Dosage recommendations are expressed as total grams of the aztreonam/avibactam combination; each 2 g vial contains aztreonam 1.5 g and avibactam 500 mg in a 3:1 ratio.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Dosage recommendations are expressed as total grams of the aztreonam/avibactam combination; each 2 g vial contains aztreonam 1.5 g and avibactam 500 mg in a 3:1 ratio.
Altered kidney function:
CrCl >50 mL/minute: IV: No dosage adjustment necessary.
CrCl >30 to ≤50 mL/minute: IV: Loading dose: 2.67 g once, followed by 1 g every 6 hours.
CrCl >15 to ≤30 mL/minute: IV: Loading dose: 1.8 g once, followed by 900 mg every 8 hours.
CrCl ≤15 mL/minute: IV: Loading dose: 1.33 g once, followed by 900 mg every 12 hours.
Hemodialysis, intermittent: IV: Loading dose: 1.33 g once, followed by 900 mg every 12 hours. Administer dose after hemodialysis on dialysis days.
No dosage adjustment necessary.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults and may include incidences for an unapproved use and concomitant therapy with metronidazole.
>10%: Hepatic: Hepatic impairment (15%; including hepatic injury, increased liver enzymes [increased serum alanine aminotransferase, increased serum aspartate aminotransferase])
1% to 10%:
Cardiovascular: Flushing (<5%), hypotension (<5%), phlebitis (<5%)
Dermatologic: Dermatitis (<5%; including allergic dermatitis), erythema of skin (<5%), skin rash (<5%; including macular eruption)
Endocrine & metabolic: Hypokalemia (6%)
Gastrointestinal: Abdominal pain (<5%), ageusia (<5%), Clostridioides difficile-associated diarrhea (<5%; including Clostridioides difficile colitis), constipation (<5%), diarrhea (6%), nausea (<5%), vomiting (<5%)
Hematologic & oncologic: Anemia (8%), disorders of hemostatic component of blood (<5%), eosinophilia (<5%), leukocytosis (<5%), thrombocytopenia (<5%), thrombocytosis (<5%)
Nervous system: Asthenia (<5%), dizziness (<5%), headache (<5%), mental status changes (<5%; including confusion, delirium, disorientation), sleep disorder (<5%; including insomnia)
Respiratory: Bronchospasm (<5%)
Miscellaneous: Fever (6%; including hyperpyrexia, hyperthermia)
Frequency not defined: Hypersensitivity: Hypersensitivity reactions
Hypersensitivity to aztreonam, avibactam, or any component of the formulation.
Concerns related to adverse effects:
• Hepatotoxicity: Elevations in hepatic transaminases have been observed. Consider discontinuation if transaminase elevations occur.
• Hypersensitivity reactions: Hypersensitivity reactions, including bronchospasm, flushing, and rash, have been reported. Establish if the patient has a history of hypersensitivity reaction to either avibactam or aztreonam prior to treatment. Immediately discontinue use and institute appropriate supportive measures if a hypersensitivity reaction occurs.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Kidney impairment: Dosage adjustment required in patients with CrCl <50 mL/minute.
Special populations:
• Bone marrow transplantation: Use with caution in patients undergoing bone marrow transplant with multiple risk factors for toxic epidermal necrolysis (TEN) (eg, sepsis, radiation therapy, concomitant therapy known to cause TEN); rare cases of TEN have been reported in association with aztreonam in this population.
Emblaveo: FDA approved February 2025; availability anticipated in 3rd quarter of 2025.
IV: Administer by IV infusion over 3 hours.
Intra-abdominal infection: Treatment of complicated intra-abdominal infection (in combination with metronidazole) in patients ≥18 years of age with limited or no alternative options, caused by the following susceptible organisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, or Serratia marcescens.
Aztreonam/avibactam may be confused with ceftazidime/avibactam.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Probenecid: May increase serum concentration of Avibactam. Risk X: Avoid
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Aztreonam crosses the human placenta (Ref); refer to the Aztreonam monograph for additional information.
In animal reproduction studies conducted with avibactam, fetal malformations were not observed in rats or rabbits. In rabbit studies, adverse events were observed in doses ≥5 times the maximum recommended human dose (based on AUC).
Aztreonam is present in breast milk; excretion of avibactam is not known.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Refer to the Aztreonam monograph for additional information.
LFTs prior to initiation and periodically during treatment, especially in patients with baseline liver disease or concomitant hepatotoxic medication use; serum creatinine prior to initiation and periodically during treatment; monitor for hypersensitivity and skin reactions.
Aztreonam is a monobactam that inhibits bacterial peptidoglycan cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to bacterial cell lysis and death.
Avibactam is a beta-lactamase inhibitor that acts by forming a covalent adduct with the enzyme that is stable to hydrolysis.
Distribution: Vd: Steady state: Aztreonam: 21.4 ± 23 L; Avibactam: 37.8 ± 73 L.
Protein binding: Aztreonam: 38%; Avibactam 8%.
Half-life elimination: Aztreonam: 2.03 ± 0.69 hours; Avibactam: 2.04 ± 0.52 hours.
Excretion: Urine (aztreonam 64.2% to 75.9% as unchanged drug; avibactam 83.8% to 100% as unchanged drug); feces (aztreonam ~12%; avibactam <0.25%).
Molecular weight: Avibactam: 287.23; Aztreonam: 435.43.
Anti-infective considerations:
Parameters associated with efficacy:
Aztreonam: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC) and AUC24 to MIC ratio. Data suggest the aztreonam PK/PD index does not change in the presence of avibactam (Singh 2015).
Organism specific:
Gram-negative organisms (including Pseudomonas aeruginosa): Goal: 50% to 60% fT > MIC (bacteriostatic); ≥65% fT > MIC (bactericidal) (Crandon 2013; Ramsey 2016).
Avibactam (in combination with aztreonam): Time dependent, associated fT above threshold concentration (CT); in combination with aztreonam CT = 2 to 2.5 mg/L. Aztreonam concentrations of 50% to 100% fT > MIC, when combined with avibactam ~25% fT > CT = 2.5 mg/L achieved stasis and ≥40% fT > CT = 2.5mg/L achieved ≥1 log reduction (Nichols 2018; Singh 2015). Avibactam goal: 50% fT > CT = 2.5 mg/L (Cornely 2020; Nichols 2018).
Expected drug concentrations in normal kidney function:
Adults:
3-hour infusion, steady state: Aztreonam 2 g/avibactam 0.67 g followed by aztreonam 1.5 g/avibactam 0.5 g every 6 hours:
AUC: IV: Aztreonam 841.22 ± 317.59 mg•hour/L; avibactam 165.7 ± 65.63 mg•hour/L.
Cmax (peak): IV: Aztreonam: 54.46 ± 17.22 mg/L; avibactam 11.29 ± 3.89 mg/L.
Postantibiotic effect: Minimal postantibiotic effect (PAE) (<1 hour) demonstrated by aztreonam for specific gram-negative bacilli (including no PAE for P. aeruginosa) (Hanberger 1990; Pillar 2016; Ramsey 2016). Post beta-lactamase inhibitory effect was not demonstrated with avibactam when combined with aztreonam (Pillar 2016).
