Novel agents in development for the treatment of resistant Gram-negative infections

Introduction: Several novel agents are in advanced stages of clinical development, potentially expanding our treatment options against third- and fourth-generation cephalosporin-resistant and carbapenem-resistant Gram-negative bacteria (GNB), including those pathogens for which the current number of effective treatments is limited. Areas covered: This review focuses on agents that have completed or ongoing phase-3 studies. A PubMed search was conducted up to 31 May 2024. Expert opinion: Novel agents in late-stage clinical development belong to the β-lactam or β-lactam/β-lactamase inhibitor combinations class and display variable antimicrobial activity depending on the specific β-lactamases expressed by GNB, particularly carbapenemases. While many of these novel agents demonstrate in vitro activity against carbapenem-resistant GNB, their efficacy has mainly been evaluated in phase-3 randomized controlled trials (RCT) for infections caused by carbapenem-susceptible GNB. Although evidence from real-world observational studies is generally less robust than that from RCT, it could be crucial for updating clinical guidelines on treating carbapenem-resistant GNB with these new agents in the absence of dedicated RCT.