mNGS Rapid Diagnosis of Brain Abscess: A Case Study

Metagenomic next-generation sequencing (mNGS) rapid diagnosis offers a critical advantage in central nervous system (CNS) infections where traditional culture methods are slow and frequently negative. Clinicians at Taipei Veterans General Hospital (TVGH) presented two cases of Fusobacterium nucleatum-associated cerebral abscess in which mNGS identified the causative pathogen within 24 hours, days before conventional culture results became available. These cases illustrate how mNGS can change the trajectory of patient care when time-to-diagnosis directly impacts clinical outcomes.

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Key Takeaways

Brain abscess cultures are negative in up to 63% of cases due to fastidious organisms and prior antibiotic exposure
mNGS identified Fusobacterium nucleatum within 24 hours in both blood and abscess specimens, compared to 12 days for conventional culture
Early pathogen identification enabled targeted antibiotic therapy (piperacillin-tazobactam) instead of broad-spectrum empiric coverage
mNGS detected the pathogen even when blood culture returned negative, providing actionable results from the abscess specimen alone
Polymicrobial brain abscesses occur in 4-33% of cases, making unbiased detection methods particularly valuable

Why Brain Abscess Diagnosis Remains a Clinical Challenge

Brain abscess, defined as a collection of pus within brain tissue, is relatively uncommon in developed countries but carries substantial mortality without prompt treatment. Delays in diagnosis and surgical intervention directly worsen patient outcomes, particularly when the causative organism is not identified and antibiotic therapy remains empiric.

The diagnostic challenge stems from multiple factors. Standard practice recommends obtaining at least two sets of blood cultures before initiating antibiotics, but administration of empiric antibiotics before sample collection, which is common in emergency settings, significantly reduces culture sensitivity for anaerobic organisms. Even under optimal conditions, conventional culture methods are time-consuming: bacterial cultures require 24-48 hours minimum, and anaerobic organisms may take considerably longer to grow.

The statistics are stark. Up to 63% of brain abscess cultures remain negative, either because the pathogen is fastidious, because prior antibiotics have suppressed growth, or because the organism is simply not recoverable by conventional culture techniques. While monomicrobial infections are most common, polymicrobial abscesses account for 4-33% of cases, further complicating culture-based identification.

Brain abscesses arise from multiple sources: hematogenous spread (20-35% of cases), contiguous infections (25-50%) such as sinusitis, dental infections, otitis media, and mastoiditis, and direct inoculation from trauma or surgical procedures. The diverse etiology means the causative organism cannot be predicted from the clinical presentation alone, making unbiased detection methods essential.

Case 1: 55-Year-Old Female with Multiple Brain Abscesses

A 55-year-old woman presented with intermittent fever, nausea, and vomiting. Physical examination revealed decreased consciousness (Glasgow Coma Scale E3V4M6) and left-sided hemiparesis. Laboratory results showed leukocytosis, elevated C-reactive protein (CRP), and elevated lactate.

Initial CT imaging revealed multiple abscesses with midline deviation. MRI confirmed a dominant right frontal abscess measuring approximately 4.3 x 3.4 centimeters with marked perifocal edema, superior extension, and mass effect causing midline shift. The patient was admitted to the neurological intensive care unit (ICU).

Empiric antibiotic therapy with vancomycin and ceftriaxone was initiated. On day 4, surgical drainage was performed without complication, and specimens were sent for both conventional culture and mNGS analysis.

The mNGS results arrived first. Within 24 hours, mNGS identified Fusobacterium nucleatum in both blood and brain abscess specimens. The patient’s fever subsided on day 10. Conventional culture of the abscess specimen confirmed Fusobacterium nucleatum on day 12, a full week after the mNGS result. Blood culture returned negative.

With the mNGS-derived pathogen identification and susceptibility profile, the antibiotic regimen was modified to piperacillin-tazobactam plus metronidazole, targeted therapy for anaerobic infection. The patient improved gradually and was discharged on day 28 with a two-week course of oral antibiotics.

Case 2: 58-Year-Old Male Initially Misdiagnosed as Stroke

A 58-year-old man presented to the emergency department with five days of headache and fever. No focal neurological signs were found on examination. The initial brain CT showed no mass lesion, only a small area suspected to be recent cerebral infarction. Based on cerebrospinal fluid (CSF) analysis from lumbar puncture, meningitis was initially suspected, and the patient was admitted to the infectious disease ward.

All initial cultures were negative. Subsequent brain MRI revealed a ring-enhancing lesion in the right parietal area measuring approximately 3.7 x 2.6 centimeters, raising suspicion for brain abscess rather than infarction or meningitis.

Surgical intervention was performed, and specimens from both the abscess cavity and blood were sent for mNGS and conventional culture. mNGS identified Fusobacterium nucleatum within 24 hours from the brain abscess specimen, providing the definitive diagnosis and enabling targeted antimicrobial therapy.

This case highlights how brain abscess can mimic other CNS pathology on initial imaging. Without the rapid pathogen identification from mNGS, the diagnostic uncertainty would have persisted through the days-long wait for culture results, delaying targeted therapy.

Fusobacterium nucleatum: The Anaerobe Behind Both Cases

Fusobacterium nucleatum is a strict anaerobic bacterium commonly found in the human oral cavity, gastrointestinal tract, urogenital tract, and upper respiratory tract. While it is part of the normal human microflora, it is increasingly recognized as a significant pathogen in abscess formation, including brain abscesses.

As an obligate anaerobe, F. nucleatum is particularly difficult to recover by conventional culture. It requires specialized anaerobic culture conditions, grows slowly, and is readily suppressed by the empiric broad-spectrum antibiotics typically administered before cultures are obtained. These characteristics make it an ideal candidate for mNGS-based detection, where viability is irrelevant and even DNA from non-viable organisms can be sequenced and identified.

The identification of the same organism in two independent cases at the same institution underscores that F. nucleatum-associated brain abscess, while uncommon, is a recurring clinical entity that benefits from rapid molecular diagnostics.

How mNGS Accelerates Clinical Decision-Making in CNS Infections

The turnaround time advantage in these cases was substantial. mNGS provided species-level pathogen identification within 24 hours, compared to 12 days for conventional culture in Case 1 and negative cultures in Case 2’s blood specimens. This difference is clinically meaningful: every day on empiric broad-spectrum antibiotics rather than targeted therapy increases the risk of adverse drug effects, promotes antimicrobial resistance, and may be less effective against the actual pathogen.

For CNS infections specifically, the clinical value of rapid identification is amplified. The blood-brain barrier limits antibiotic penetration, making drug selection critical. Knowing the pathogen enables selection of antimicrobials with optimal CNS penetration and activity against the specific organism, rather than relying on empiric combinations that attempt to cover all possibilities.

mNGS workflows that include host depletion using the Devin Host Depletion Filter further improve sensitivity by removing the overwhelming human DNA background from clinical specimens. Combined with the PaRTI-Seq analysis pipeline for rapid bioinformatic classification, the complete workflow delivers actionable pathogen identification within the 24-hour timeframe demonstrated in these TVGH cases.

As mNGS technology matures, its role in CNS infections is likely to expand beyond abscess to include meningitis, encephalitis, and ventriculitis, conditions where culture-negative results are common and diagnostic delays carry severe consequences.

About the Speaker

Dr. Po-Hsiang Liao – Attending Physician, Emergency Department, Taipei Veterans General Hospital Dr. Yen-Chia Chen – Department Chief (corresponding author), Taipei Veterans General Hospital