{{Short description|Chemical compound}} {{Infobox drug | IUPAC_name = [(2''S'',5''R'')-2-Carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl] hydrogen sulfate | image = Avibactam structure 2.svg | image_class = skin-invert-image | width = 200 | image2 = Avibactam ball-and-stick model.png | image_class2 = bg-transparent | alt = | caption =
<!-- Clinical data --> | tradename = Avycaz (formulated with ceftazidime) | Drugs.com = | MedlinePlus = | DailyMedID = Avibactam | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_category= | routes_of_administration = Intravenous therapy
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> | legal_US = Rx-only | legal_status =
<!-- Pharmacokinetic data --> | bioavailability = 100% (intravenous) | protein_bound = 5.7–8.2%<ref>{{cite web|title=Full Prescribing Information: Avycaz (ceftazidime-avibactam) for Injection, for intravenous use|url=http://pi.actavis.com/data_stream.asp?product_group=1957&p=pi&language=E|archive-url=https://web.archive.org/web/20150602094121/http://pi.actavis.com/data_stream.asp?product_group=1957&p=pi&language=E|url-status=dead|archive-date=2 June 2015|publisher=©2015 Actavis. All rights reserved.|access-date=1 June 2015}}</ref> | metabolism = Nil | onset = Increases in proportion to dose | elimination_half-life = | excretion = Kidney (97%)
<!-- Identifiers --> | CAS_number = 1192500-31-4 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 7352665165 | ATCvet = | ATC_prefix = None | ATC_suffix = | PubChem = 9835049 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 85984 | ChemSpiderID = 8010770 | KEGG = D10340 | DrugBank =
<!-- Chemical data --> | chemical_formula = | C=7 | H=11 | N=3 | O=6 | S=1 | smiles= NC([C@H]1[N@](C(N2OS(O)(=O)=O)=O)C[C@H]2CC1)=O | ChEMBL = 1689063 | StdInChI = 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 | StdInChIKey = NDCUAPJVLWFHHB-UHNVWZDZSA-N }}
'''Avibactam''' is a non-β-lactam β-lactamase inhibitor<ref>{{cite journal | vauthors = Wang DY, Abboud MI, Markoulides MS, Brem J, Schofield CJ | title = The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam | journal = Future Medicinal Chemistry | volume = 8 | issue = 10 | pages = 1063–1084 | date = June 2016 | pmid = 27327972 | doi = 10.4155/fmc-2016-0078 | doi-access = free }}</ref> developed by Actavis (now Teva) jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime was approved by the FDA in 2015 for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) caused by antibiotic-resistant pathogens, including those caused by multidrug resistant Gram-negative bacterial pathogens.<ref>{{cite journal | vauthors = Zhanel GG, Lawson CD, Adam H, Schweizer F, Zelenitsky S, Lagacé-Wiens PR, Denisuik A, Rubinstein E, Gin AS, Hoban DJ, Lynch JP, Karlowsky JA | display-authors = 6 | title = Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination | journal = Drugs | volume = 73 | issue = 2 | pages = 159–177 | date = February 2013 | pmid = 23371303 | doi = 10.1007/s40265-013-0013-7 | s2cid = 32700350 | url = https://zenodo.org/record/1230313 }}</ref><ref>{{cite web|title=Actavis Announces FDA Acceptance of the NDA Filing for Ceftazidime-Avibactam, a Qualified Infectious Disease Product|url=http://www.actavis.com/news/news/thomson-reuters/actavis-announces-fda-acceptance-of-the-nda-filing|website=Actavis—a global, integrated specialty pharmaceutical company—Actavis|publisher=Actavis plc|access-date=1 June 2015|archive-url=https://web.archive.org/web/20150527032942/http://www.actavis.com/news/news/thomson-reuters/actavis-announces-fda-acceptance-of-the-nda-filing|archive-date=27 May 2015|url-status=dead}}</ref><ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Kinetics of avibactam inhibition against Class A, C, and D β-lactamases | journal = The Journal of Biological Chemistry | volume = 288 | issue = 39 | pages = 27960–27971 | date = September 2013 | pmid = 23913691 | pmc = 3784710 | doi = 10.1074/jbc.M113.485979 | doi-access = free }}</ref>
Increasing resistance to cephalosporins among Gram-negative 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.<ref>{{cite journal | vauthors = Abboud MI, Damblon C, Brem J, Smargiasso N, Mercuri P, Gilbert B, Rydzik AM, Claridge TD, Schofield CJ, Frère JM | display-authors = 6 | title = Interaction of Avibactam with Class B Metallo-β-Lactamases | journal = Antimicrobial Agents and Chemotherapy | volume = 60 | issue = 10 | pages = 5655–5662 | date = October 2016 | pmid = 27401561 | pmc = 5038302 | doi = 10.1128/AAC.00897-16 }}</ref>
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.<ref>{{cite journal | vauthors = Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L | title = The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases | journal = Antibiotics | volume = 10 | issue = 8 | pages = 1012 | date = August 2021 | pmid = 34439062 | pmc = 8388901 | doi = 10.3390/antibiotics10081012 | doi-access = free }}</ref> Avibactam is available in a combination with aztreonam (aztreonam/avibactam; Emblaveo) and with meropenem (meropenem/avibactam; Meropran-AV).
== References == {{reflist}}
== Further reading == {{refbegin}} * {{cite conference | vauthors = Edeki T, Armstrong J, Li J | title = Pharmacokinetics of avibactam (AVI) and ceftazidime (CAZ) following separate or combined administration in healthy volunteers. | id = Poster A-1019 | conference = 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) | date = September 2013 | volume = 10 | page = 13 |url= http://www.icaaconline.com/php/icaac2014abstracts/data/papers/2013/A/2013_A-1019.htm |url-status=dead |archive-url= https://web.archive.org/web/20160303213124/http://www.icaaconline.com/php/icaac2014abstracts/data/papers/2013/A/2013_A-1019.htm |archive-date=2016-03-03 }} {{refend}}
{{Cell wall disruptive antibiotics|state=collapsed}}
Category:Antibiotics Category:Beta-lactamase inhibitors Category:Nitrogen heterocycles Category:Organosulfates