Colistin Resistance in Healthcare: Mechanisms and Management

In the battle against multidrug-resistant bacteria, colistin has emerged as a critical last-resort antibiotic. However, the rising tide of colistin resistance poses a significant threat to its efficacy, necessitating an urgent understanding of the underlying mechanisms and their clinical implications.

Colistin operates by disrupting the bacterial cell membrane, making it highly effective against Gram-negative pathogens. This process is, however, increasingly undermined by genetic mutations and the presence of mobile colistin resistance (MCR) genes. These factors have contributed to reported increases in resistance, limiting therapeutic options for severe infections, as noted in recent research.

Beyond plasmid-borne MCR genes that directly add phosphoethanolamine to lipid A, chromosomal mutations in lipid A biosynthesis and regulatory pathways can also lead to phosphoethanolamine or 4-amino-4-deoxy-L-arabinose additions, which reduces colistin affinity. Across Gram-negatives, resistance spreads largely via horizontal transfer of mcr genes, while analogous chromosomal adaptations arise independently within species.

To manage these challenges, antimicrobial stewardship programs (ASPs) emerge as vital tools, emphasizing surveillance, restrictive policies, and clinician education. They offer strategic frameworks for surveillance and restrictive use policies and for educating healthcare providers, aligning implementation with local resistance trends.

Recognizing these challenges sets the stage for adaptive stewardship plans, including dynamic formulary restrictions and diagnostic-driven de-escalation, essential for combating the evolving threat of antibiotic resistance.

Building on stewardship, advanced diagnostics—such as rapid phenotypic AST or mcr PCR—guide targeted use and combination therapy decisions, offering promising pathways to develop robust treatment protocols that eclipse current limitations.

Key Takeaways:

• The impact of MCR genes and chromosomal mutations substantially affects colistin's effectiveness through lipid A modifications that reduce drug affinity.
• Stewardship programs are crucial in managing the surge in antibiotic resistance.
• Advanced diagnostic tools provide new avenues for effective intervention.