Biology:Avibactam

Short description: Chemical compound

Avibactam

Clinical data
Trade names	Avycaz (formulated with ceftazidime)
License data	EU EMA: by INN
Pregnancy category	US: B (No risk in non-human studies)
Routes of administration	IV
ATC code	None
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	100% (intravenous)
Protein binding	5.7–8.2%
Metabolism	Nil
Onset of action	Increases in proportion to dose
Excretion	Renal (97%)
Identifiers
IUPAC name [(2S,5R)-2-Carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl] hydrogen sulfate
CAS Number	1192500-31-4
PubChem CID	9835049
ChemSpider	8010770
UNII	7352665165
KEGG	D10340
ChEBI	CHEBI:85984 Y
ChEMBL	ChEMBL1689063
Chemical and physical data
Formula	C7H11N3O6S
Molar mass	265.24 g·mol−1
3D model (JSmol)	Interactive image
SMILES [C@]12C[N@]([C@@H](CC1)C(N)=O)C(=O)N2OS(O)(=O)=O
InChI InChI=1S/C7H11N3O6S/c8-6(11)5-2-1-4-3-9(5)7(12)10(4)16-17(13,14)15/h4-5H,1-3H2,(H2,8,11)(H,13,14,15)/t4-,5+/m1/s1 Key:NDCUAPJVLWFHHB-UHNVWZDZSA-N

Avibactam is a non-β-lactam β-lactamase inhibitor 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.

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.

For infections sustained by metallo-β-lactamases producing bacteria, a therapeutic strategy consists in administering avibactam as companion drug administered alongside aztreonam. In fact, although in theory aztreonam is not hydrolyzed by metallo-β-lactamases, many metallo-β-Lactamases-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g. AmpC, ESBL), therefore avibactam is given to protect aztreonam exploiting its robust β-lactamases inhibition.

See also

• Relebactam
• Durlobactam

Further reading

• "Pharmacokinetics of avibactam (AVI) and ceftazidime (CAZ) following separate or combined administration in healthy volunteers.". 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). 10. September 2013. p. 13. Poster A-1019. http://www.icaaconline.com/php/icaac2014abstracts/data/papers/2013/A/2013_A-1019.htm.