Considerations and caveats in anti-virulence drug development

- ESKAPE bacteria are ideal candidates for anti-virulence drugs due to their multi-drug resistance.
- Careful target selection to avoid resistance and maximize anti-virulence compound efficacy.
- Study parameters need to evolve to accommodate the unique aspects of anti-virulence drugs.

As antibiotic resistance remains a major public health threat, anti-virulence therapy research is gaining interest. Hundreds of potential anti-virulence compounds have been examined, but very few have made it to clinical trials and none have been approved. This review surveys the current anti-virulence research field with a focus on the highly resistant and deadly ESKAPE pathogens, especially Pseudomonas aeruginosa. We discuss timely considerations and caveats in anti-virulence drug development, including target identification, administration, preclinical development, and metrics for success in clinical trials. Development of a defined pipeline for anti-virulence agents, which differs in important ways from conventional antibiotics, is imperative for the future success of these critically needed drugs.

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