Chest Infections Section
An evolving diagnostic tool: Microbial cell-free DNA
The diagnosis of the microbial etiology of pneumonia remains a significant challenge with <50% yield of blood and sputum cultures in most studies. More reliable samples, like bronchoalveolar lavage, require invasive procedures. Undifferentiated pneumonia hampers antimicrobial stewardship and increases the risk of suboptimal treatment. New diagnostic tools that detect degraded microbial DNA in plasma, known as microbial cell-free DNA (cfDNA), may offer improved diagnostic yield. Through metagenomic next-generation approaches, these tools sequence DNA fragments to identify viral, bacterial, and fungal sequences.
Dr. Gregory Wigger
Earlier studies of cfDNA in pneumonia have been mixed, correctly identifying the pathogen in 55% to 86% of cases – though notably cfDNA was superior to PCR and cultures and provided early detection of VAP in some cases (Farnaes L, et al. Diagn Microbiol Infect Dis. 2019;94:188; Langelier C, et al. Am J Respir Crit Care Med. 2020;201:491). However, a recent study of cfDNA in severe complicated pediatric pneumonia had promising results with significant clinical impact. cfDNA provided an accurate microbial diagnosis in 89% of cases, with it being the only positive study in 70% of cases. Further, cfDNA narrowed the antimicrobial regimen in 81% of cases (Dworsky ZD, et al. Hosp Pediatr. 2022;12:377).
The use of cfDNA is still in its infancy. Limitations, such as a lack of validated thresholds to differentiate colonization vs infection are noted given its detection sensitivity. Its utility, including ideal timing and patient population, needs further investigation. However, diagnostic cfDNA may soon provide earlier and less invasive microbial diagnostics in patients with chest infections and beyond.
Gregory Wigger, MD
Section Fellow-in-Training