Avibactam

Avibactam
Clinical data
Trade names	Avycaz (formulated with ceftazidime)
Routes of; administration	Intravenous therapy
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	Kidney (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 ;
ChEMBL	ChEMBL1689063;
CompTox Dashboard (EPA)	DTXSID901026066 ;
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^[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]

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]

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.^[7] Avibactam is available in a combination with aztreonam (aztreonam/avibactam).