Avibactam

Avibactam
Clinical data
Trade names	Avycaz (formulated with ceftazidime)
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;
KEGG	D10340;
ChEBI	CHEBI:85984 ;
ChEMBL	ChEMBL1689063;
Chemical and physical data
Formula	C7H11N3O6S
Molar mass	265.24 g/mol 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 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

^ "Full Prescribing Information: AVYCAZ™ (ceftazidime-avibactam) for Injection, for intravenous use". ©2015 Actavis. All rights reserved. Retrieved 1 June 2015.
^ 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.
^ 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.
^ "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.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ 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

T. Edeki; J. Armstrong; J. Li. "Pharmacokinetics of Avibactam (AVI) and Ceftazidime (CAZ) Following Separate or Combined Administration in Healthy Volunteers". Archived from the original on 2016-03-03. {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

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[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 3784710. PMID 23913691.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[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.

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