Title : A culture-negative multisystem abscess syndrome: Unmasking Fusobacterium vincentii through cell-free DNA sequencing
Abstract:
Background: Culture-negative central nervous system (CNS) abscesses pose substantial diagnostic challenges. Early antibiotic exposure, complex anatomy, and fastidious pathogens frequently limit the yield of conventional microbiologic testing. We present a case that illustrates the value of incorporating next-generation sequencing into the diagnostic algorithm for suspected anaerobic CNS infections.
Case Presentation: A 55-year-old man with chronic alcohol use presented with several weeks of subacute non-bloody diarrhea, progressive generalized weakness, and encephalopathy, meeting sepsis criteria with fever, tachycardia, tachypnea, hypoxia, marked leukocytosis, elevated lactate, and elevated procalcitonin. Initial infectious work-up, including serial blood cultures, was unrevealing. Imaging identified a right upper lobe cavitary lesion with bronchiectasis, mediastinal lymphadenopathy, and sigmoid diverticulitis with possible microperforation, along with a small subdural hematoma. Empiric antibiotics were broadened and later narrowed to ceftriaxone and metronidazole. MRI brain revealed multifocal peripherally enhancing lesions with restricted diffusion, consistent with multiple brain abscesses and possible pyogenic ventriculitis. The patient's course was further complicated by bilateral lower-extremity DVTs and acute pulmonary embolism.
An extensive evaluation - CSF culture and multiplex PCR, fungal and AFB studies, MTB PCR, toxoplasma and EBV testing, Aspergillus and cryptococcal studies, culture-negative endocarditis serologies, and echocardiography - failed to identify a causative organism. CSF showed lymphocytic pleocytosis with positive oligoclonal bands, initially raising concern for demyelinating disease or metastasis. A large paraspinal collection was identified on cross-sectional imaging; image-guided aspiration yielded minimal, culture-negative fluid, and no tissue diagnosis was obtained from the CNS, lung, or paraspinal lesions despite prolonged anti-anaerobic therapy. After weeks without a diagnosis, cell-free DNA sequencing (Karius) identified Fusobacterium vincentii, unifying the pulmonary, abdominal, paraspinal, and CNS findings as a single hematogenous anaerobic process.
Discussion: This case demonstrates how culture-negative multisystem infection can evade standard diagnostic testing when anti-anaerobic therapy and low-yield sampling limit organism recovery. The patient's risk factors - alcohol use, aspiration risk, and diverticular disease offered multiple plausible portals of entry, while the prothrombotic complications paralleled known fusobacterial pathophysiology.
Conclusion: When tissue sampling is unsafe or unattainable and cultures/serologies remain exhaustively negative, cell-free DNA sequencing should be considered to identify anaerobic pathogens in patients with multifocal brain abscesses and multisystem involvement. Early integration of advanced molecular diagnostics into culture-negative, multisystem abscess syndromes may accelerate diagnosis, guide targeted therapy, and reduce morbidity.
