(1048) Needle in a Haystack: Disseminated Nocardiosis and New Frontiers in Infectious Disease Diagnosis

Introduction: Nocardiosis is a bacterial infection that most commonly presents as pneumonia in the immunocompromised, but can also occur as brain abscess or meningoencephalitis. Diagnosis can be difficult as culture and acid-fast staining have low sensitivity, and brain imaging is non-specific in cases of meningitis or meningoencephalitis. We present a case of nocardia meningoencephalitis diagnosed by next-generation sequencing (NGS).

Description: A 57-year-old man with history of HIV/AIDS with CD4 count of 5, pneumocystis pneumonia, and intravenous drug use had a prolonged hospital stay for work up of a right upper lobe cavitary lesion. Transbronchial biopsy was negative for tuberculosis and malignancy, and cultures were negative. He was receiving antiretrovirals and trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. On day 24 he developed refractory convulsive status epilepticus, requiring endotracheal intubation, and was transferred to the Neuroscience ICU. Intravenous sedatives were titrated to achieve burst suppression. Cefepime, vancomycin, and acyclovir were given for empiric meningoencephalitis coverage. CSF showed 92 WBCs with a polymorphonuclear predominance, 650 RBCs, protein of 95, and glucose of 23. A multipathogen PCR panel and cultures were negative. MRI brain showed small foci of contrast enhancement within bilateral basal ganglia and subcortical white matter along perivascular spaces but no meningeal enhancement. Because the etiologic agent was not elucidated by routine testing, CSF was sent for 16s ribosomal RNA NGS, and blood sent for microbial cell free DNA NGS. Both returned positive for Nocardia farcinica. The patient was started on triple therapy for disseminated nocardiosis with amikacin, meropenem, and TMP-SMX. He improved neurologically but required tracheostomy on day 43. He was transferred to a subacute rehabilitation on day 65.

Discussion: This case demonstrates the utility of NGS to diagnose infections when conventional tests are unrevealing. These tests are high-sensitivity and potentially less invasive methods to diagnose infection when cultures are unrevealing and obtaining tissue samples is high-risk (e.g. brain biopsy) or not practical. NGS testing earlier in the course may have prevented development of meningoencephalitis and subsequent significant complications.