Clinical application of targeted nanopore sequencing in pathogen detection in patients with sepsis

Abstract

Abstract Background Precision in detecting pathogens in sepsis patients is crucial for deploying targeted therapeutic strategies. The objective of the present investigation was to assess the efficacy of targeted nanopore sequencing (TNPseq) as a method for detecting sepsis pathogens. Methods For this investigation, we stratified 90 patients with sepsis into ‘improved’ and ‘unimproved’ groups based on their clinical outcomes. Pathogenic microorganisms were detected in various sample types on the day of sepsis diagnosis, utilizing both conventional culture and TNPseq techniques. A comparative analysis of these methodologies was undertaken to assess their performance and efficacy in identifying pathogens in sepsis infections and discern pathogens with significant differences between the distinct patient groups. Results The TNPseq analysis demonstrated superior performance in detecting pathogens in sepsis patients, achieving a significantly higher positivity rate (94.4%) compared to the culture method (30.0%, p < 0.001). TNPseq offered enhanced detection capabilities across a diverse array of pathogen types and sample types, outperforming culture particularly in the identification of fungi (35 vs. 8), viruses (46 vs. 1), and atypical pathogens. Both TNPseq and culture yielded concurrent positive results in 26 patient samples, yet TNPseq identified additional pathogens in 14 of these samples. A notable discrepancy in the types of infections was observed between the ‘improved’ and ‘unimproved’ groups, with a higher prevalence of single infections among the ‘improving’ cohort (p < 0.05). Significant differences in the incidence of Acinetobacter baumannii and Clostridium striatum were also evident between the two groups, underscoring the importance of focusing on these two pathogens in future clinical diagnostic efforts. Conclusion This study underscores the versatility of TNPseq in identifying diverse pathogens in sepsis samples, ensuring its application as a diagnostic when pathogens elude conventional isolation or are difficult to culture. It particularly highlights the significant differences of A. baumannii and C. striatum in the two patient groups, pointing to potential research directions. TNPseq’s potential in sepsis diagnosis is promising.

Keywords

• Sepsis
• TNPseq
• Culture
• Diagnostic
• Pathogenic microorganism