Clinical data | |
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Trade names | Avycaz (formulated with ceftazidime) |
Routes of administration | Intravenous therapy |
ATC code |
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Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | 100% (intravenous) |
Protein binding | 5.7–8.2% [1] |
Metabolism | Nil |
Onset of action | Increases in proportion to dose |
Excretion | Kidney (97%) |
Identifiers | |
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CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
Chemical and physical data | |
Formula | C7H11N3O6S |
Molar mass | 265.24 g·mol−1 |
3D model ( JSmol) | |
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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).
Clinical data | |
---|---|
Trade names | Avycaz (formulated with ceftazidime) |
Routes of administration | Intravenous therapy |
ATC code |
|
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 | Kidney (97%) |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
Chemical and physical data | |
Formula | C7H11N3O6S |
Molar mass | 265.24 g·mol−1 |
3D model ( JSmol) | |
| |
|
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).