Antibiotics in development for multiresistant gram-negative bacilli.

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Rising antibiotic resistance in Gram-negative bacilli (GNB), particularly Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, presents a critical global health challenge.
• Extensively drug-resistant (XDR) strains necessitate the development of novel therapeutic strategies to combat infections.

Purpose of the Study:

• To review the landscape of novel antibiotic agents and combinations developed to address XDR GNB infections.
• To evaluate the in vitro and in vivo efficacy of these agents, with a focus on activity against metallo-β-lactamases (MBLs).

Main Methods:

• Literature review of recently developed antibiotics and combinations targeting XDR GNB.
• Analysis of in vitro susceptibility data against various β-lactamase classes, including MBLs.
• Assessment of clinical trial status and approved agents.

Main Results:

• Several new antibiotic combinations and agents, including aztreonam/avibactam, cefepime/zidebactam, and cefiderocol, demonstrate activity against MBLs.
• Existing combinations like ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam lack activity against MBLs.
• Some novel agents are approved, while others are in clinical development to establish their therapeutic role.

Conclusions:

• Novel antibiotic strategies are emerging to combat XDR GNB, offering new hope against challenging pathogens.
• Agents with activity against MBLs are crucial for treating infections caused by resistant Gram-negative bacteria.
• Further clinical studies are essential to define the optimal use of these new antibiotics in patient care.