Circulating Cell-Free DNA for Brain Abscess Diagnosis: A Pilot Study

Brain abscess is a severe intracranial infection associated with significant morbidity and mortality. Standard management combines neurosurgical intervention, when feasible, with prolonged intravenous antibiotic therapy. Neurosurgical procedures, such as surgical drainage or stereotactic aspiration, play a key role in reducing intracranial pressure, decreasing the infectious burden, and obtaining samples for microbiological identification. However, neurosurgical intervention is not always possible due to technical limitations or patien related contrindications. In these situations, microbiological documentation becomes particularly challenging. Conventional diagnostic methods have limited sensitivity, with blood cultures and lumbar puncture yielding positive results in only about 25% of brain abscess cases. Recent advances in infectious disease diagnostics have introduced metagenomic approaches that may improve pathogen detection. Studies have shown that metagenomic analysis of operative samples can provide more comprehensive microbiological documentation than conventional culture-based methods. In addition, next-generation sequencing (NGS) of circulating microbial cell-free DNA in blood enables the detection of short microbial DNA fragments with a short half-life, reflecting active infection. This technology has already demonstrated promising results in clinical situations where microbiological documentation is difficult, such as febrile neutropenia. The present study aims to evaluate the performance of this approach in patients with brain abscess.