Combination antibiotic medication
Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor.[4] It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia.[4][5] It is only recommended when other options are not appropriate.[4] It is given by infusion into a vein.[4]
Common side effect include nausea, fever, liver problems, headache, trouble sleeping, and pain at the site of infusion.[4] Severe side effects may include anaphylaxis, seizures, and Clostridioides difficile-associated diarrhea.[4] While use appears to be safe in pregnancy the medication has not been well studied in this group.[6] Doses should be adjusted in those with kidney problems.[7] Ceftazidime works by interfering with the building of the bacterial cell wall while avibactam works by preventing ceftazidime's breakdown.[4]
The combination was approved for medical use in the United States and the European Union in 2015.[4][5] It is on the World Health Organization's List of Essential Medicines.[8] Resistances are increasingly been reported with United States, Greece and Italy accounting for 80% of cases.[9]
Medical use
Ceftazidime/avibactam is used to treat certain multidrug-resistant gram-negative infections.[10]
Ceftazidime/avibactam is used for the treatment of:
Bacterial activity
For many bacterial infections, it offers little or no advantage over ceftazidime monotherapy, due to the widespread expression of resistance mechanisms other than β-lactamase production. These include Haemophilus, Moraxella and Neisseria pathogens, and infections caused by Acinectobacter baumannii.[10]
The antibacterial spectrum of ceftazidime/avibactam includes nearly all Enterobacteriaceae, including ceftazidime-resistant strains. The activity of ceftazidime/avibactam against the important hospital pathogen Pseudomonas aeruginosa is variable, due to the potential presence of other resistance mechanisms in addition to β-lactamase production. Synergy was observed for avibactam with ceftazidime in Burkholderia infections.[12]
Adverse events
When used to treat life-threatening infections, ceftazidime/avibactam is more likely than carbapenem antibiotics to cause serious adverse events, including worsening kidney function and gastrointestinal adverse effects.[13]
Mechanism of action
Bacterial resistance to cephalosporins is often due to bacterial production of β-lactamase enzymes that deactivate these antibiotics. Avibactam inhibits some (but not all) bacterial β-lactamases. Also, some bacteria are resistant to cephalosporins by other mechanisms, and therefore avibactam doesn't work. Avibactam is not active against New Delhi metallo-β-lactamase 1 (NDM-1).[14] Avibactam inhibits Klebsiella pneumoniae carbapenemases (KPCs), and AmpC-type β-lactamases, which are resistant to the other clinically available β-lactamases, tazobactam and clavulanic acid.[15]
Regulatory
It was granted approval for marketing in the United States by the Food and Drug Administration (FDA) in February 2015.[16] It was granted approval for marketing in Europe by the European Medicines Agency in 2016. During its clinical development, ceftazidime/avibactam was designated as a Qualified Infectious Disease Product under the Generating Antibiotic Incentives Now provision of the Food and Drug Administration Safety and Innovation Act.[17][18] Development of ceftazidime/avibactam was fast-tracked by the FDA due to the shortage of drugs for treatment of infections due to antibiotic-resistant bacteria.[citation needed]
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