Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-negative Organisms

Effect of β-Lactamase inhibitors on in vitro activity of β-Lactam antibiotics against Burkholderia cepacia complex species

“…Intrinsic resistance to a wide range of antimicrobial agents, including aminoglycosides, polymyxin, first and second generation cephalosporins, carboxypenicillins and other β-lactam antibiotics is frequently observed in Bcc strains. Resistance of Gram-negative microorganisms to β-lactam molecules is most commonly mediated by inducible or constitutively expressed β-lactamases, efflux pumps or alterations in PBPs [8, 9]. β-lactamase was first identified in 1940 as penicillinase in Escherichia coli even before the clinical use of penicillin, and has since been identified in a variety of other bacteria, including species of the Bcc [10–13].…”

“…They do so by binding to PBPs, resulting in a decreased cross-linking of peptidoglycan in the cell wall, eventually leading to cell death [8, 14]. The utility of β-lactams has become compromised through the increasing presence of both chromosomally and plasmid-encoded β-lactamase enzymes.…”

“…Finally, class D β-lactamases (also known as oxacillinases), are active against a broad range of β-lactam antibiotics. Clavulanic acid, sulbactam nor tazobactam inhibit these enzymes, but avibactam inhibits some class D enzymes [8, 10, 14]. …”

Efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs): A meta-analysis of randomized controlled trials

“…13,14 Ceftazidime--avibactam was recently granted accelerated approval by the FDA for the treatment of CUTIs and CIAIs combined with metronidazole in adult patients when treatment options are limited. 16 Ceftazidime-avibactam is an antibacterial agent that consists of an existing third-generation cephalosporin combined with a novel β-lactamase inhibitor. An important advantage of ceftazidime-avibactam is that avibactam can expand the antibacterial activity of ceftazidime against Enterobacteriaceae and P. aeruginosa by inhibiting AmpC, extended-spectrum β-lactamase, and carbapenemase producing strains.…”

What is the role of the new β-lactam/β-lactamase inhibitors ceftolozane/tazobactam and ceftazidime/avibactam?

“…The main pharmacokinetic features of TOL/TAZ are the following: rapid tissue distribution, low protein binding, nonclinically significant drug-drug interactions via the cytochrome P450 (CYP450) enzymes, lung penetration, and extensive renal excretion [21]. CAZ/AVI has similar pharmacokinetics [22]. Both are administered only parenterally [23].…”