The global resistance problem and the clinical antibacterial pipeline.

A comprehensive analysis of the clinical antibacterial pipeline demonstrates that there is a limited range of strategies that are primarily focused on modified versions of widely used chemical classes. These modifications aim to circumvent class-specific resistance mechanisms and reduce resistance rates in certain multidrug-resistant pathogens. Owing to the great variation in resistance rates and mechanisms, the clinical success of current approaches varies substantially across different countries, regions, and economic and environmental conditions, which affects the global societal value of these antibiotics that remain vulnerable to cross-resistance. Although there has been some progress in developing urgently needed antibiotics with novel targets and chemical structures, some of which have advanced to phase I/II trials, further breakthroughs are required. Additionally, adjunctive agents designed to enhance the outcome of conventional antibiotic therapies, along with bacteriophages that offer targeted and personalized treatments, are also under investigation. However, the potential of adjunctive therapeutics, such as antivirulence agents, and bacteriophages has yet to be realized in terms of feasibility and global societal impact.