Evolutionary ecology meets the antibiotic crisis: Can we control pathogen adaptation through sequential therapy?

Area of Science:

• Evolutionary Medicine
• Microbial Ecology
• Infectious Disease Therapeutics

Background:

• Antibiotic resistance is a critical global health challenge driven by evolutionary and ecological factors.
• Current therapeutic strategies often overlook these fundamental biological processes.
• Evolutionary medicine principles are essential for designing sustainable anti-infective treatments.

Purpose of the Study:

• To highlight sequential antibiotic therapy as a neglected yet promising treatment strategy.
• To explore how evolutionary trade-offs can optimize sequential treatment designs.
• To provide an overview of sequential therapy and propose optimization steps.

Main Methods:

• Review and commentary on existing sequential antibiotic therapy strategies.
• Analysis of evolutionary principles, including collateral sensitivity and negative hysteresis.
• Discussion of how fluctuating selection pressures can be leveraged against pathogens.

Main Results:

• Sequential therapy creates fluctuating antibiotic-induced selection conditions that are difficult for microbes to overcome.
• Exploiting evolutionary trade-offs, such as collateral sensitivity and inducible hyper-sensitivity (negative hysteresis), can enhance treatment efficacy.
• Optimized sequential treatment designs offer a sustainable approach to managing antibiotic resistance.

Conclusions:

• Sequential antibiotic therapy represents a viable strategy to combat the spread of antibiotic resistance.
• Integrating evolutionary principles into treatment design is crucial for long-term effectiveness.
• Further research and implementation of optimized sequential therapy are warranted.