Ceftazidime/avibactam

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Ceftazidime/avibactam
Ceftazidime and avibactam.svg
Combination of
CeftazidimeCephalosporin antibiotic
Avibactamβ-lactamase inhibitor
Clinical data
Trade namesAvycaz, Zavicefta
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa615018
License data
Pregnancy
category
  • US: B (No risk in non-human studies)
Routes of
administration
Intravenous infusion
ATC code
Legal status
Legal status
Identifiers
PubChem CID
KEGG
 ☒N☑Y (what is this?)

Ceftazidime/avibactam ( proprietary names: Avycaz, Zavicefta)[1] is a combination drug composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used for the treatment of serious bacterial infections.

Medical use[edit]

Ceftazidime/avibactam was developed for the treatment of certain multidrug-resistant gram-negative infections.[2]

Ceftazidime/avibactam is used for the treatment of:

  • complicated intra-abdominal infections. In these cases it is often used in combination with metronidazole, which provides coverage for anaerobic pathogens.
  • complicated urinary tract infections, including acute pyelonephritis, in adults.
  • hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.[3]

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.[4]

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 the Burkholderia cepacia complex.[5]

According to the full prescribing information, its use should be avoided unless the bacteria causing infection is susceptible to ceftazidime/avibactam, so as to avoid development of widespread resistance to the drug.

Mechanism of action[edit]

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 ß-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).[6] 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.[7]

Adverse events[edit]

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.[8]

Regulatory[edit]

It was granted approval for marketing in the United States by the FDA in February 2015.[9] 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.[10][11] 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.

References[edit]

  1. ^ "Briefing package: ceftazidime-avibactam. Anti-infective drugs advisory committee meeting" (PDF). fda.gov. U.S. Food and Drug Administration. Retrieved 27 June 2015.
  2. ^ Lagacé-Wiens P, Walkty A, Karlowsky JA (2014). "Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections". Core Evid. 9: 13–25. doi:10.2147/CE.S40698. PMC 3908787. PMID 24493994.
  3. ^ https://www.allergan.com/assets/pdf/avycaz_pi
  4. ^ Lagacé-Wiens P, Walkty A, Karlowsky JA (2014). "Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections". Core Evid. 9: 13–25. doi:10.2147/CE.S40698. PMC 3908787. PMID 24493994.
  5. ^ Mushtaq S, Warner M, Livermore DM (2010). "In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters". J Antimicrob Chemother. 65 (11): 2376–2381. doi:10.1093/jac/dkq306. PMID 20801783.
  6. ^ Lohans CT, Brem J, Schofield CJ (December 2017). "New Delhi Metallo-β-Lactamase 1 Catalyzes Avibactam and Aztreonam Hydrolysis". Antimicrob. Agents Chemother. 61 (12). doi:10.1128/AAC.01224-17. PMC 5700305. PMID 28971873.
  7. ^ "www.accessdata.fda.gov" (PDF).
  8. ^ Sternbach N, Leibovici Weissman Y, Avni T, Yahav D (August 2018). "Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis". J. Antimicrob. Chemother. 73 (8): 2021–2029. doi:10.1093/jac/dky124. PMID 29659836.
  9. ^ http://tools.wmflabs.org/citation-template-filling/cgi-bin/index.cgi?ddb=&type=url&id=http%3A%2F%2Fwww.accessdata.fda.gov%2Fscripts%2Fcder%2Fdrugsatfda%2Findex.cfm%3Ffuseaction%3DSearch.Label_ApprovalHistory%23labelinfo
  10. ^ "Press Announcements - FDA approves new antibacterial drug Avycaz". www.fda.gov. Retrieved 2015-11-16.
  11. ^ "FDA clears Actavis' combination antibacterial Avycaz". www.firstwordpharma.com. Retrieved 2015-11-16.

External links[edit]