Heteroresistance in Gram-Negative Bacteria: Diagnostic Challenges, Clinical Impact, and Emerging Strategies to Overcome Antimicrobial Resistance

Abstract

Background: Globally, heteroresistance (HR) significantly hinders the fight against antimicrobial resistance in Gram-negative bacteria. It is a key contributor to treatment failure, prolonged hospital stays, and increased mortality rates due to its transient nature, difficulty in detection, and role in promoting high-level resistance, which complicates treatment outcomes.

Main Body: This review highlights the need for improved diagnostic tools and targeted therapeutic strategies to overcome HR. Current AST methods are insufficient, while advanced molecular techniques are more accurate but remain underutilised due to cost and technical limitations. Emerging technologies such as single-cell sequencing, next-generation sequencing (NGS), and AI-driven diagnostics hold promise for immediate and accurate HR detection, potentially transforming clinical practice. The major hindrance preventing these approaches from routine clinical use includes standardising detection protocols and integrating novel therapeutics, such as anti-virulence strategies and CRISPR-based gene editing.

Conclusion:

This review underscores the importance of global antibiotic stewardship, AI-driven diagnostic tools, and continued research into the evolution of HR and its clinical implications. Standardising HR detection procedures and integrating advanced molecular technologies will enhance early detection, optimise therapeutic interventions, and preserve the efficacy of last-resort antibiotics. Future research should focus on developing standardised protocols, addressing knowledge gaps in the evolution of HR, and implementing global stewardship policies to mitigate its emergence and improve patient outcomes in bacterial infections.