Clinical translation of polymyxin-based combination therapy: Facts, challenges and future opportunities

Area of Science:

• Infectious Diseases
• Pharmacology
• Translational Medicine

Background:

• Rising multidrug-resistant Gram-negative bacteria necessitates the re-evaluation of polymyxin antibiotics.
• Polymyxin resistance is increasing, driving interest in combination therapy to preserve antibiotic efficacy.
• Challenges exist in identifying optimal polymyxin combinations and understanding their clinical safety and effectiveness.

Purpose of the Study:

• To review the obstacles hindering the clinical implementation of polymyxin combination therapy.
• To emphasize the need for translational research to bridge the gap between basic science and clinical practice.
• To identify future research priorities for effective polymyxin combination strategies.

Main Methods:

• Literature review of existing studies on polymyxin combination therapy.
• Analysis of factors impeding the translation of research findings to clinical settings.
• Discussion of translational research insights and future research directions.

Main Results:

• Significant challenges exist in selecting effective and safe polymyxin combinations due to diverse and sometimes conflicting data.
• A knowledge gap persists in translating preclinical data into clinically applicable guidelines for polymyxin combinations.
• Translational research is vital for addressing ambiguities and facilitating bedside application of polymyxin combination therapy.

Conclusions:

• Overcoming hurdles in polymyxin combination therapy requires a concerted effort in translational research.
• Addressing knowledge gaps is essential for the successful clinical integration of polymyxin combinations.
• Future research should focus on generating robust evidence to guide optimal polymyxin combination use against resistant infections.