Avibactam

Avibactam is a non-β-lactam β-lactamase inhibitor[2] developed by Actavis (now Teva) jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime (branded as Avycaz) was approved by the FDA on February 25, 2015, for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) caused by antibiotic resistant-pathogens, including those caused by multi-drug resistant Gram-negative bacterial pathogens.[3][4][5]

Avibactam
Clinical data
Trade namesAvycaz (formulated with ceftazidime)
License data
Pregnancy
category
  • US: B (No risk in non-human studies)
    Routes of
    administration    		IV
    ATC code
    • None
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability100% (intravenous)
    Protein binding5.7–8.2%[1]
    MetabolismNil
    Onset of actionIncreases in proportion to dose
    ExcretionRenal (97%)
    Identifiers
    CAS Number
    PubChem CID
    ChemSpider
    KEGG
    ChEBI
    ChEMBL
    Chemical and physical data
    FormulaC7H11N3O6S
    Molar mass265.24 g/mol g·mol−1
    3D model (JSmol)

    Increasing resistance to cephalosporins among Gram-(−) bacterial pathogens, especially among hospital-acquired infections, results in part from the production of β-lactamase enzymes that deactivate these antibiotics. While the co-administration of a β-lactamase inhibitor can restore antibacterial activity to the cephalosporin, previously approved β-lactamase inhibitors such as tazobactam and clavulanic acid do not inhibit important classes of β-lactamases, including Klebsiella pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamase 1 (NDM-1), and AmpC-type β-lactamases. Whilst avibactam inhibits class A (KPCs, CTX-M, TEM, SHV), class C (AmpC), and, some, class D serine β-lactamases (such as OXA-23, OXA-48), it has been reported to be a poor substrate/weak inhibitor of class B metallo-β-lactamases, such as VIM-2, VIM-4, SPM-1, BcII, NDM-1, Fez-1.[6]

    See also
    • Relebactam

    References
    1. "Full Prescribing Information: AVYCAZ™ (ceftazidime-avibactam) for Injection, for intravenous use". ©2015 Actavis. All rights reserved. Retrieved 1 June 2015.
    2. Wang, David Yuxin; Abboud, Martine I; Markoulides, Marios S; Brem, Jürgen; Schofield, Christopher J (2016-06-01). "The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam". Future Medicinal Chemistry. 8 (10): 1063–1084. doi:10.4155/fmc-2016-0078. ISSN 1756-8919.
    3. Zhanel, GG (2013). "Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination" (PDF). Drugs. 73 (2): 159–77. doi:10.1007/s40265-013-0013-7. PMID 23371303.
    4. "Actavis Announces FDA Acceptance of the NDA Filing for Ceftazidime-Avibactam, a Qualified Infectious Disease Product". Actavis—a global, integrated specialty pharmaceutical company—Actavis. Actavis plc. Retrieved 1 June 2015.
    5. Ehmann, DE; Jahic, H; Ross, PL; Gu, RF; Hu, J; Durand-Réville, TF; Lahiri, S; Thresher, J; Livchak, S; Gao, N; Palmer, T; Walkup, GK; Fisher, SL (2013). "Kinetics of Avibactam Inhibition against Class A, C, and D β-Lactamases". The Journal of Biological Chemistry. 288 (39): 27960–71. doi:10.1074/jbc.M113.485979. PMC 3784710. PMID 23913691.
    6. Abboud, Martine I.; Damblon, Christian; Brem, Jürgen; Smargiasso, Nicolas; Mercuri, Paola; Gilbert, Bernard; Rydzik, Anna M.; Claridge, Timothy D. W.; Schofield, Christopher J.; Frère, Jean-Marie (2016-07-11). "Interaction of Avibactam with Class B Metallo-β-lactamases". Antimicrobial Agents and Chemotherapy. 60: AAC.00897–16. doi:10.1128/AAC.00897-16. ISSN 0066-4804. PMC 5038302. PMID 27401561.


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