A70-28 Hard to Diagnose, Harder to Treat: A Case of Culture-Delayed Disseminated Tuberculosis Complicated by Isoniazid Neurotoxicity

Abstract Introduction Disseminated tuberculosis (TB) is challenging to diagnose due to the limited sensitivity of acid-fast bacilli (AFB) stains and cultures. Management can be complicated by drug toxicities, including - rarely - isoniazid neurotoxicity. CASE REPORT: A 66-year-old female retired nurse from the Philippines with end-stage renal disease (ESRD) and a history of latent TB (treated with rifampin in 2023) was admitted with diverticular bleeding and incidentally found to have diffuse thoracoabdominal lymphadenopathy and pulmonary nodules. Urgent outpatient supraclavicular lymph node biopsy revealed necrotizing granulomas with negative AFB stains, prompting Infectious Disease referral. Prior to further evaluation, the patient was readmitted with abdominal pain. Abdominal CT showed ascites, pleural effusions, peritoneal thickening, and omental infiltration. Peritoneal fluid studies demonstrated elevated total nucleated cell count with lymphocytic predominance; pleural fluid studies were exudative. Both peritoneal and pleural fluid had elevated adenosine deaminase (ADA) levels (53.6 and 36.0, respectively) but negative AFB stains. Mediastinal lymph node and omental biopsies redemonstrated necrotizing granulomas with negative AFB, Fite, and fungal stains. Nucleic acid amplification tests of biopsy and induced sputum samples were also negative for TB. Shortly after discharge, peritoneal cultures grew AFB (later speciated as Mycobacterium tuberculosis), so the patient was empirically started on treatment for multi-drug resistant TB, then switched to RIPE-L (rifampin, isoniazid, pyrazinamide, ethambutol, levofloxacin) based on susceptibilities. However, one week after starting RIPE-L, the patient was readmitted with confusion. CT Head, MRI Brain, and EEG were unrevealing. Levofloxacin and ethambutol were held due to concerns for drug-related neurotoxicity, but her encephalopathy did not improve. Ultimately, the patient’s encephalopathy rapidly resolved after cessation of isoniazid and up-titration of pyridoxine, consistent with isoniazid neurotoxicity. Discussion This case highlights the diagnostic challenges of extrapulmonary TB and a rare manifestation of isoniazid toxicity. Given the limited sensitivity of AFB stains and cultures for peritoneal/pleural TB (0-10% for stains, 23-69% for cultures), ADA is a useful adjunct. ADA levels >40 are nearly 100% sensitive and 97% specific for peritoneal TB and 89-99% sensitive and >90% specific for pleural TB. However, ADA has a modest positive predictive value as it can be elevated in malignancy and non-tuberculous infections. Regarding isoniazid neurotoxicity, peripheral neuropathies occur in up to 6.5% of patients, but central neurotoxicity - presenting as encephalopathy, psychosis, or seizures - is rare. Patients on hemodialysis are at increased risk of central neurotoxicity due to abnormal pyridoxine metabolism and increased clearance of pyridoxine during dialysis. This abstract is funded by: None