New antimicrobial substances to combat increasing resistance

Antimicrobial resistance (AMR) represents a major and escalating global health threat, with an estimated 4.71 million deaths associated with AMR in 2021 and 1.14 million directly attributable to infections caused by multidrug-resistant organisms, particularly multidrug-resistant Gram-negative bacteria such as resistant Enterobacterales, Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, which the World Health Organization identifies as priority pathogens. In response, advances in rapid diagnostics and the approval of several new antibiotics over the past decade have expanded treatment options, largely through modifications of existing antibiotic classes, including novel β-lactam/β-lactamase inhibitor combinations, the siderophore cephalosporin cefiderocol, and agents such as eravacycline and dalbavancin. Regulatory changes, notably in Germany, now allow certain new antibiotics to be designated as reserve agents, facilitating their clinical uptake, while the antibiotic development pipeline—previously near stagnation—has begun to recover with new compounds targeting novel mechanisms entering clinical trials, alongside emerging alternative approaches such as monoclonal antibodies, antimicrobial peptides, microbiome-based therapies, and bacteriophages aimed at more targeted and personalized treatment strategies.