Bringing Precision Medicine to the ICU: Insights from BugSeq Grant Recipient Dr. Georgios Kitsios¶
In 2024, BugSeq awarded a research grant to Dr. Georgios Kitsios, physician-scientist and Associate Professor of Medicine at the University of Pittsburgh. Dr. Kitsios leads innovative research in applying metagenomic sequencing to critical care medicine—specifically, tackling the challenge of ventilator-associated pneumonia (VAP), a life-threatening infection that affects up to half of mechanically ventilated patients. Our team at BugSeq was excited by his team’s VAP-MAPS project, which is harnessing cutting-edge nanopore sequencing and advanced bioinformatics to bring rapid, actionable diagnostics to the ICU. We caught up with Dr. Kitsios to learn more about the project and how his team is using BugSeq to advance VAP diagnostics.
Insights from Dr. Georgios Kitsios¶
You were the BugSeq grant awardee for 2024, working on metagenomics sequencing for VAP, could you tell us more about why this work is important and what you were hoping to achieve?¶
Ventilator-associated pneumonia affects up to 50% of mechanically ventilated patients and remains a major contributor to mortality and antibiotic overuse in ICUs. Traditional culture methods are slow and insensitive, often taking days to provide results while patients deteriorate. Our VAP-MAPS project leverages Nanopore metagenomics on 420 longitudinal samples from 180 critically ill patients to develop rapid pathogen detection and antimicrobial resistance profiling. We’re hoping to create a diagnostic framework that can identify VAP pathogens and predict antibiotic susceptibility within hours rather than days, ultimately improving patient outcomes while reducing unnecessary antibiotic use.
How is NGS becoming more important for the patient population in comparison to conventional laboratory testing techniques?¶
NGS provides comprehensive, culture-independent detection of all microorganisms present in clinical samples, including fastidious pathogens that traditional cultures often miss. Unlike conventional methods that can take 2-3 days and frequently yield negative results, metagenomics can deliver results within hours and simultaneously detect antimicrobial resistance genes. This is particularly crucial for critically ill patients where every hour of inappropriate antibiotic therapy increases mortality risk. Our Nature Communications study showed that lung microbiome profiles are stronger predictors of clinical outcomes than traditional clinical variables, highlighting the diagnostic potential that conventional methods cannot capture.
What were the main challenges your team was facing when it came to data analysis?¶
The primary challenge was the limitation of standard bioinformatics platforms, which lack sophisticated antimicrobial resistance detection capabilities and comprehensive pathogen labeling systems. We needed robust analytical tools that could accurately identify AMR genes, correlate their abundance with clinical antibiograms, and provide clinically interpretable pathogen profiles. Additionally, we required advanced clustering algorithms to identify potential clinical misclassifications and distinguish true VAP cases from colonization. The complexity of metagenomic data demanded specialized analytical frameworks that could translate raw sequencing data into actionable clinical insights.
How did BugSeq enable you to overcome those challenges?¶
BugSeq’s automated bioinformatics platform provided the enhanced AMR detection and comprehensive metagenomic analytics that standard platforms couldn’t deliver. Their sophisticated algorithms enable us to examine meaningful abundance thresholds for AMR genes that correlate with clinical antibiograms, moving beyond simple presence/absence detection. The platform’s advanced pathogen labeling system allows us to distinguish between true pathogens and colonizing organisms, which is critical for VAP diagnosis. BugSeq’s clinical-grade analytics transformed our raw Nanopore sequencing data into interpretable reports that our clinical team could use for diagnostic decision-making, bridging the gap between genomic data and clinical practice.
Where do you see the biggest value of BugSeq in clinical settings?¶
The biggest value lies in BugSeq’s ability to provide rapid, comprehensive pathogen identification with antimicrobial susceptibility prediction in real-time clinical scenarios. The platform’s strength is translating complex metagenomic data into clinically relevant insights that can guide antibiotic stewardship and improve patient outcomes. With the results obtained from BugSeq, we will be able to perform expert reviewer analysis to allow us to infer potential impact on clinical decision-making and patient outcomes. For critically ill patients where diagnostic delays can be fatal, BugSeq’s rapid turnaround and comprehensive analysis could revolutionize infection management by enabling precision medicine approaches in the ICU setting.
What are you working on in 2025 and how are you hoping to incorporate using BugSeq going forward?¶
In 2025, we’re wrapping up analyses from our VAP-MAPS project and preparing for publication of these important findings. We’re also expanding our research to incorporate gut microbiota analysis, focusing on how resistant organisms harbored in the gut can later translocate and cause multidrug-resistant organism (MDRO) infections. We plan to use BugSeq’s advanced analytics to infer genetic relatedness of organisms detected in both gut and lung samples, allowing us to better understand the gut-lung axis and microbial translocation patterns. This comprehensive approach will help us identify high-risk patients and develop targeted interventions to prevent MDRO infections in critically ill patients.
Conclusion¶
Dr. Kitsios’s work exemplifies how genomic technologies, paired with robust clinical analytics, can change the trajectory of infectious disease care. By combining large-scale metagenomic sequencing with BugSeq’s advanced antimicrobial resistance detection and pathogen profiling, his team is bridging the gap between research and real-time patient care. As the VAP-MAPS project nears completion and expands into studying the gut-lung axis of multidrug-resistant infections, the potential impact on precision medicine in critical care is profound. BugSeq is proud to support researchers like Dr. Kitsios who are pushing the boundaries of what’s possible in infectious disease diagnostics—and bringing those innovations directly to the bedside.