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| Trade names | Avycaz (formulated with ceftazidime) |
| Routes of administration | Intravenous therapy |
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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%) |
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| Formula | C7H11N3O6S |
| Molar mass | 265.24 g·mol−1 |
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Avibactam is a non-β-lactamβ-lactamase inhibitor[2] developed byActavis (nowTeva) jointly withAstraZeneca. Anew drug application for avibactam incombination with ceftazidime was approved by the FDA in 2015 for treating complicatedurinary tract (cUTI) and complicatedintra-abdominal infections (cIAI) caused byantibiotic-resistant pathogens, including those caused by multidrug resistantGram-negative bacterial pathogens.[3][4][5]
Increasing resistance tocephalosporins among Gram-negative bacterial pathogens, especially among hospital-acquired infections, results in part from the production ofβ-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 astazobactam andclavulanic acid do not inhibit important classes of β-lactamases, includingKlebsiella pneumoniaecarbapenemases (KPCs),New Delhi metallo-β-lactamase 1 (NDM-1), andAmpC-type β-lactamases. Whilst avibactam inhibits class A (KPCs, CTX-M, TEM, SHV), class C (AmpC), and some class D serineβ-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 alongsideaztreonam. 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 robustβ-lactamases inhibition.[7] Avibactam is available in a combination with aztreonam (aztreonam/avibactam; Emblaveo) and withmeropenem (meropenem/avibactam; Meropran-AV).
