Comparative Evaluation of Sequencing Technologies for Detecting Antimicrobial Resistance in Bloodstream Infections

Bloodstream infections (BSIs) represent a critical global health concern, particularly in the face of rising antimicrobial resistance (AMR). Prompt and accurate detection of pathogens and resistance determinants is essential for effective treatment and improved patient outcomes. However, traditional culture-based diagnostic methods suffer from prolonged turnaround times and limited sensitivity, particularly in culture-negative or polymicrobial infections. This review provides a comprehensive evaluation of current and emerging sequencing technologies for AMR detection in BSIs, including whole-genome sequencing (WGS), targeted next-generation sequencing (tNGS), metagenomic next-generation sequencing (mNGS), and long-read sequencing platforms such as Oxford Nanopore and PacBio. We discuss their underlying principles, clinical performance, turnaround times, and ability to detect known and novel resistance genes. Key metrics such as clinical sensitivity, diagnostic yield, and cost-effectiveness are compared, along with their integration into clinical workflows and antimicrobial stewardship programs. The review highlights the potential of sequencing to revolutionize BSI diagnostics through rapid, culture-independent detection and personalized antimicrobial therapy. While each method presents unique advantages and limitations, a context-specific, hybrid diagnostic approach is recommended for optimal clinical utility. Future perspectives, including AI-driven prediction of phenotypic resistance and multi-omic integration, are also explored as pathways to enhancing precision infectious disease diagnostics.