Innovative Pairing of Beta-Lactamase Inhibitors to Combat Multidrug-Resistant Gram-Negative Pathogens

An expanding repertoire of beta-lactamase inhibitors is increasingly relied upon to protect antibiotics against antibiotic-resistant pathogens.

Resistance to antimicrobials has multifactorial mechanisms, and the ability of pathogens to hydrolyze beta-lactam (BL) antibiotics through broad-spectrum beta-lactamases has propagated an “arms race” between antibiotic drug developers and increasingly resistant bacteria dating back to the introduction of penicillin in the 1940s.

Classical beta-lactamase inhibitors (BLIs) such as sulbactam, clavulanic acid, and tazobactam were initially paired with BLs such as ampicillin, amoxicillin, or piperacillin. More recently, tazobactam has been paired with a novel cephalosporin, ceftolozane (Zerbaxa; approved for the treatment of complicated urinary tract infection [cUTI], complicated intra-abdominal infection [cIAI] when combined with metronidazole, …

Author

George Sakoulas, MD

Disclosures

Consultant/Advisory BoardParatek Pharmaceuticals; Nestle Corp.; AbbVie; Shionogi

Speaker’s BureauAllergan/AbbVie; Paratek Pharmaceuticals; Nestle Corp.

RoyaltiesUpToDate

Editorial BoardsAntimicrobial Agents and Chemotherapy; Open Forum Infectious Diseases