Ceftazidime/Avibactam (Avycaz)

The Pharmacy and Therapeutics Committee approved the addition of ceftazidime/avibactam (Avycaz) to the inpatient formulary July 2021 with use restricted to the infectious diseases (ID) services. A class review for antibiotics active against carbapenem resistant gram-negative pathogens can be found at the bottom of the page.

Efficacy

Ceftazidime/avibactam is a cephalosporin/beta-lactamase inhibitor combination. It has activity against resistant aerobic gram-negative bacteria (Enterobacterales) and carbapenem resistant Pseudomonas aeruginosa. Avibactam protects ceftazidime from degradation and is active against narrow and extended spectrum beta-lactamases (TEM/SHV, CTX-M), AmpC, and carbapenemases including KPC and OXA-48 like. Clinical trials have found it to be noninferior to carbapenems in the treatment of complicated urinary tract infections, nosocomial pneumonia, and complicated intra-abdominal infection (when combined with metronidazole), leading to its FDA-approved indications for these infections.

Safety

Ceftazidime/avibactam has similar adverse effects compared to other cephalosporins and was generally well tolerated in clinical trials. Most adverse reactions were designated as mild or moderate, with the most common being nausea/vomiting and diarrhea. In patients with complicated intra-abdominal infections, patients with renal insufficiency (creatinine clearance 30-50 ml/min) had lower cure rates in the clinical trial. The dose that is FDA approved is higher than what was used in this trial but necessitates caution when using this medication for that indication in patients with renal insufficiency.  

Uniqueness

Ceftazidime/avibactam offers a needed treatment option for multi-drug resistant gram-negative infections. Additionally, it is the only novel agent that is FDA approved for use in pediatric patients greater than 3 months old. Studies have demonstrated the addition of aztreonam may expand its activity against metallo-beta lactamases such as NDM, providing a treatment option that may have activity against all major carbapenemases.

Restrictions

• Any use will require review and approval by the Infectious Diseases (ID) Service. The ordering physician is responsible for contacting the ID service.
• The drug will be started with a 24-hour stop date unless approval for continued use is obtained; therefore, the approval must be received within 24 hours of the original order. If use is approved, the ID Service will relay this information to the ordering physician as well as to the pharmacy for continued administration of ceftazidime/avibactam.
• If ceftazidime/avibactam is thought to be inappropriate, the ID Service will provide alternative recommendations and communicate these recommendations to the physician originating the ceftazidime/avibactam order.

Criteria for Use

• Should only be used when there is documented or strong suspicion for infection due to multidrug-resistant Pseudomonas aeruginosa or carbapenem resistant Enterobacterales with no alternative treatment options.
• For mixed infections, ceftazidime/avibactam must be used in combination with agents possessing gram-positive and/or anaerobic activity

Dosing Recommendations

Ceftazidime/avibactam has approved indications for pediatric patients ≥3 months old. Refer to packaging labeling or a drug information reference for specific dosing.

Formulary class review for agents active against carbapenem-resistant Gram-negative bacilli