Ceftazidime/avibactam

Ceftazidime/avibactam
Combination of
CeftazidimeCephalosporin antibiotic
Avibactamβ-lactamase inhibitor
Names
Trade namesAvycaz, Zavicefta, others[1]
Clinical data
Drug classAntibiotic
Main usesIntra abdominal infections, urinary tract infections, pneumonia[2][3]
Side effectsNausea, fever, liver problems, headache, trouble sleeping, pain at the site of injection[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: B (No risk in non-human studies)
    Routes of
    use    		Intravenous infusion
    Defined daily dosenot established[4]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa615018
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only

    Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor.[2] It is used to treat complicated intra abdominal infections, urinary tract infections, and pneumonia.[2][3] It is only recommended when other options are not appropriate.[2] It is given by injection into a vein.[2]

    Common side effect include nausea, fever, liver problems, headache, trouble sleeping, and pain at the site of injection.[2] Severe side effects may include anaphylaxis, seizures, and Clostridium difficile-associated diarrhea.[2] While use appears to be safe in pregnancy the medication has not been well studied in this group.[5] Doses should be adjusted in those with kidney problems.[6] Ceftazidime works by interfering with the building of the bacterial cell wall while avibactam works by preventing ceftazidime's breakdown.[2]

    The combination was approved for medical use in the United States and Europe in 2015.[2][3] It is on the World Health Organization's List of Essential Medicines.[7] In the United States a course of treatment generally costs between US$7,500 to US$15,000 as of 2016.[6] In the United Kingdom this amount costs the NHS about £1,800 to £3,600 as of 2019.[8]

    Medical use

    Ceftazidime/avibactam is used to treat certain multidrug-resistant gram-negative infections.[9]

    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.[6]
    • complicated urinary tract infections, including acute pyelonephritis, in adults.
    • hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.[10]

    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.[9]

    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.[11]

    Dosage

    The defined daily dose is not established.[4]

    Side effects

    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.[12]

    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 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).[13] 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.[14]

    Regulatory

    It was granted approval for marketing in the United States by the Food and Drug Administration (FDA) in February 2015.[15] 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.[16][17] 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

    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. 1 2 3 4 5 6 7 8 9 10 "Ceftazidime and Avibactam Sodium Monograph for Professionals". Drugs.com. Archived from the original on 25 October 2019. Retrieved 25 October 2019.
    3. 1 2 3 "Application for inclusion of ceftazidime-avibactam" (PDF). WHO. Archived (PDF) from the original on 28 August 2021. Retrieved 25 October 2019.
    4. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 11 September 2020.
    5. ↑ "Avibactam / ceftazidime (Avycaz) Use During Pregnancy". Drugs.com. Archived from the original on 25 October 2019. Retrieved 25 October 2019.
    6. 1 2 3 Mosley JF, 2nd; 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". Pharmacy and Therapeutics. 41 (8): 479–83. PMC 4959616. PMID 27504064.
    7. ↑ 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.
    8. ↑ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. X. ISBN 9780857113382.
    9. 1 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.
    10. ↑ "Archive copy". Archived from the original on 2019-06-27. Retrieved 2019-02-28.{{cite web}}: CS1 maint: archived copy as title (link)
    11. ↑ 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.
    12. ↑ 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.
    13. ↑ 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.
    14. ↑ "Clinical Review, NDA 206494, Ceftazidime-avibactam" (PDF). Food and Drug Administration (FDA). 2015-02-18. Archived (PDF) from the original on 2017-02-28. Retrieved 2015-07-24.
    15. ↑ "AVYCAZ (ceftazidime-avibactam) approval letter" (PDF). Food and Drug Administration (FDA). 2015-02-25. Archived (PDF) from the original on 2021-04-09. Retrieved September 10, 2019.
    16. ↑ "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.
    17. ↑ "FDA clears Actavis' combination antibacterial Avycaz". FirstWord Pharma. Archived from the original on 2015-11-20. Retrieved 2015-11-16.
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