Critical analysis of antibacterial agents in clinical development

Journal article : Review

The antibacterial agents currently in clinical development are predominantly derivatives of well-established antibiotic classes and were selected to address the class-specific resistance mechanisms and determinants that were known at the time of their discovery. Many of these agents aim to target the antibiotic-resistant priority pathogens listed by the WHO, including Gram-negative bacteria in the critical priority category, such as carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales. Although some current compounds in the pipeline have exhibited increased susceptibility rates in surveillance studies that depend on geography, pre-existing cross-resistance both within and across antibacterial classes limits the activity of many of the new agents against the most extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens. In particular, cross-resistance to unrelated classes may occur by co-selection of resistant strains, thus leading to the rapid emergence and subsequent spread of resistance. There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria.

Authors: Theuretzbacher, U; Bush, K; Harbarth, S; Paul, M; Rex, JH

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Reviews Microbiology More from this journal
• Volume: 18
• Issue: 5
• Pages: 286-298
• Publication date: 2020-03-09
• Acceptance date: 2020-02-12
• DOI: 10.1038/s41579-020-0340-0
• EISSN: 1740-1534
• ISSN: 1740-1526
• Pmid: 32152509
• Language: English
• Keywords: FFR
• Subtype: Review