Avibactam

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Avibactam
Avibactam structure 2.svg
Avibactam ball-and-stick model.png
Clinical data
Trade names Avycaz (formulated with ceftazidime)
Pregnancy
category
  • US: B (No risk in non-human studies)
Routes of
administration
IV
ATC code None
Legal status
Legal status
Pharmacokinetic data
Bioavailability 100% (intravenous)
Protein binding 5.7–8.2%[1]
Metabolism Nil
Onset of action Increases in proportion to dose
Excretion Renal (97%)
Identifiers
CAS Number 1192500-31-4
PubChem (CID) 9835049
ChemSpider 8010770
KEGG D10340
ChEBI CHEBI:85984 YesY
ChEMBL CHEMBL1689063
Chemical and physical data
Formula C7H11N3O6S
Molar mass 265.24 g/mol
3D model (Jmol) Interactive image

Avibactam is a non-β-lactam β-lactamase inhibitor[2] developed by Actavis (now Allergan) 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]

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, class B, and, some, class D serine β-lactamases (such as KPCs, AmpC), 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]

References[edit]

  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". 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 3784710Freely accessible. 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. (2016-07-11). "Interaction of Avibactam with Class B Metallo-β-lactamases". Antimicrobial Agents and Chemotherapy: AAC.00897–16. doi:10.1128/AAC.00897-16. ISSN 0066-4804. PMID 27401561. 

External links[edit]