Circulating Microbial Cell-Free DNA in Health and Disease
Abstract
:1. Introduction
2. Circulating cfmDNA or Contamination?
3. The Presence of Circulating cfmDNA in Patients and Healthy Individuals
4. The Potential Origin of Circulating cfmDNA
5. Potential of Circulating cfmDNA in Clinical Applications
6. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Context | Major Findings | References |
---|---|---|
Septic shock | >70% of the positivity rate for NGS-based pathogen identification over the whole study period. 96% of positive NGS results for acute sepsis time points were plausible. NGS results would have led to a change to a more adequate therapy in 53% of cases. | [30] |
Relapsed or refractory pediatric cancers | 75% and 80% of predictive sensitivity of NGS for all BSIs and bacterial BSIs, respectively, in the 3 days before the onset of infection. 82% and 91% of the specificity of NGS, for any bacterial or fungal organism and any common BSI pathogen, respectively. | [17] |
BSIs | 89.3% and 74.3% of the NGS sensitivity and specificity, respectively. NGS identified causative pathogens for a significantly longer interval than conventional blood cultures (median 15 days vs. 2 days; p < 0.0001). The odds of metastatic infection significantly increased with each additional day of circulating cfmDNA detection (odds ratio, 2.89; p = 0.0011). | [35] |
Sepsis | NGS reached the sensitivity and specificity of 0.952 and 1, respectively, for the identification of bacterial infection, and allowed for the simultaneous detection of viral pathogens. NGS revealed differences in the composition of circulating cfmDNA between septic and non-septic patients and between survivors and non-survivors by 28-day mortality. Improved performance was achieved in identifying sepsis and the prediction of clinical outcomes for ICU patients with AUC of 0.992 and 0.802, respectively, by integrating the information from circulating human and microbial cfDNA into a machine learning model. | [7] |
Infective endocarditis | NGS achieved a sensitivity of 87%. NGS identified causative pathogens for a significantly longer interval than conventional blood cultures (median duration of positivity from antibiotic treatment initiation was 38.1 days vs. 3.7 days; p = 0.02771). The level of cfmDNA significantly decreased after surgical source control. | [34] |
Periprosthetic joint infections | NGS identified causative pathogens in 57% of cases, increasing pathogen detection to 94% (as an adjunct to tissue cultures).NGS improved the time-to-speciation (the median time was 3 days less than standard-of-care methods).After treatment, NGS did not detect circulating cfmDNA of the infectious pathogen or there were reduced levels of circulating cfmDNA. | [31] |
Infected pancreatic necrosis | The positivity rate of NGS was 54.55%. 83.33% of NGS-positive cases were consistent with the culture results of infected pancreatic necrosis drains. The PPA and NPA of NGS were 80.0% and 89.47%, respectively. Patients in the NGS positive group had new-onset septic shock significantly more frequently (12 (50.0%) vs. 4 (20.0%), p = 0.039) than those in the negative group. | [32] |
Febrile neutropenia | The PPA and NPA of NGS were 90% and 31%, respectively. NGS sensitivity and specificity were 85% and 100%, respectively. NGS improved the time to diagnosis. NGS results would have led to a change to a more adequate therapy in 47% of cases. | [36] |
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Pietrzak, B.; Kawacka, I.; Olejnik-Schmidt, A.; Schmidt, M. Circulating Microbial Cell-Free DNA in Health and Disease. Int. J. Mol. Sci. 2023, 24, 3051. https://doi.org/10.3390/ijms24033051
Pietrzak B, Kawacka I, Olejnik-Schmidt A, Schmidt M. Circulating Microbial Cell-Free DNA in Health and Disease. International Journal of Molecular Sciences. 2023; 24(3):3051. https://doi.org/10.3390/ijms24033051
Chicago/Turabian StylePietrzak, Bernadeta, Iwona Kawacka, Agnieszka Olejnik-Schmidt, and Marcin Schmidt. 2023. "Circulating Microbial Cell-Free DNA in Health and Disease" International Journal of Molecular Sciences 24, no. 3: 3051. https://doi.org/10.3390/ijms24033051