Critical analysis of antibacterial agents in clinical development

• Published in: Nature reviews. Microbiology Vol. 18; no. 5; pp. 286 - 298
• Main Authors: Theuretzbacher, Ursula, Bush, Karen, Harbarth, Stephan, Paul, Mical, Rex, John H, Tacconelli, Evelina, Thwaites, Guy E
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2020
• Subjects: Acinetobacter - drug effects; Acinetobacter Infections - microbiology; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotic resistance; Antibiotics; Bacteria; Cross-resistance; Drug Development - trends; Drug discovery; Drug resistance; Drug resistance in microorganisms; Drug Resistance, Bacterial; Drug therapy; Enterobacteriaceae - drug effects; Enterobacteriaceae Infections - microbiology; Geography; Gram-negative bacteria; Gram-negative bacterial infections; Humans; Literature reviews; Microbiological research; Pathogens; Pseudomonas - drug effects; Pseudomonas Infections - microbiology; Testing; Austria
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-020-0340-0

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.