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Ceftazidime/avibactam

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Ceftazidime/avibactam
Combination of
CeftazidimeCephalosporin antibiotic
Avibactamβ-lactamase inhibitor
Clinical data
Trade namesAvycaz, Zavicefta, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa615018
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Intravenous infusion
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
KEGG
 ☒NcheckY (what is this?)

Ceftazidime/avibactam, sold under the brand name Avycaz (by AbbVie) 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

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Ceftazidime/avibactam is used to treat certain multidrug-resistant gram-negative infections.[10]

Ceftazidime/avibactam is used for the treatment of:

Bacterial activity

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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

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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

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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

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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]

References

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  1. ^ "Briefing package: ceftazidime-avibactam. Anti-infective drugs advisory committee meeting" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original (PDF) on 30 June 2015. Retrieved 27 June 2015.
  2. ^ "Avycaz- ceftazidime, avibactam powder, for solution". DailyMed. 26 January 2024. Retrieved 21 February 2024.
  3. ^ "Zavicefta EPAR". European Medicines Agency. 23 June 2016. Retrieved 21 February 2024.
  4. ^ a b c d e f g h "Ceftazidime and Avibactam Sodium Monograph for Professionals". Drugs.com. Retrieved 25 October 2019.
  5. ^ a b "Application for inclusion of ceftazidime-avibactam" (PDF). WHO. Retrieved 25 October 2019.
  6. ^ "Avibactam / ceftazidime (Avycaz) Use During Pregnancy". Drugs.com. Retrieved 25 October 2019.
  7. ^ a b Mosley JF, Smith LL, Parke CK, Brown JA, Wilson AL, Gibbs LV (August 2016). "Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal and Urinary Tract Infections". P & T. 41 (8): 479–483. PMC 4959616. PMID 27504064.
  8. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ Di Bella S, Giacobbe DR, Maraolo AE, Viaggi V, Luzzati R, Bassetti M, et al. (June 2021). "Resistance to ceftazidime/avibactam in infections and colonisations by KPC-producing Enterobacterales: a systematic review of observational clinical studies". Journal of Global Antimicrobial Resistance. 25: 268–281. doi:10.1016/j.jgar.2021.04.001. hdl:11368/2990131. PMID 33895414. S2CID 233399477.
  10. ^ a b 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.
  11. ^ "Highlights of prescribing information". allergan.com. Retrieved 22 July 2023.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ "Clinical Review, NDA 206494, Ceftazidime-avibactam" (PDF). Food and Drug Administration (FDA). 2015-02-18.
  16. ^ "AVYCAZ (ceftazidime-avibactam) approval letter" (PDF). Food and Drug Administration (FDA). 2015-02-25. Retrieved September 10, 2019.
  17. ^ "FDA approves new antibacterial drug Avycaz" (Press release). Food and Drug Administration (FDA). Archived from the original on 2015-11-17. Retrieved 2015-11-16.
  18. ^ "FDA clears Actavis' combination antibacterial Avycaz". FirstWord Pharma. Retrieved 2015-11-16.
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