1401. Infliximab for Immune Reconstitution Inflammatory Syndrome (IRIS) in Tuberculous Meningitis; A Treatment Paradox

Abstract Background Tumor necrosis factor (TNF)-α inhibitors are known for the reactivation of latent tuberculosis (TB). As a paradox, it has been reported to have a role in the treatment of immune reconstitution inflammatory syndrome (IRIS) from anti-TB therapy. Methods We report a case of paradoxical worsening of central nervous system TB after initiation of anti-TB medications, which was treated successfully with infliximab (TNF-α inhibitor). Results A 34-year-old man from Nepal with a history of untreated latent TB presented with complaints of occipital headache, slurred speech, and witnessed seizure. His physical exam was consistent with hyperreflexia. MRI of the brain revealed multiple small contrast-enhancing lesions in cerebral hemispheres. CT Chest showed bilateral centrilobular nodules suggestive of miliary TB. Cerebrospinal fluid (CSF) analysis showed pleocytosis, high protein, and low glucose. He was started on isoniazid, rifampin, ethambutol, and pyrazinamide along with high-dose dexamethasone for TB meningitis. Later, MTB DNA probe from bronchioalveolar lavage and CSF detected Mycobacterium Tuberculosis which was pan-susceptible. Repeat MRI of the brain 6 months into therapy revealed worsening of brain lesions. Moxifloxacin and linezolid were added to the regimen given clinical progression on first-line therapy. 6-months into this enhanced regimen he started experiencing blurring of vision. Visual field mapping showed left homonymous hemianopia. Repeat MRI of the brain confirmed extensive changes of basilar meningitis completely enveloping the optic chiasm. IRIS from TB was suspected. His prednisone dose was increased, and 3-doses of infliximab infusion were, 2-weeks apart were administered which showed clinical and radiological improvement. MRI Brain MRI Brain (axial T2/flair sequence) shows hyperintensities in multiple locations including the involvement of the left optic nerve and the left occipital region. Conclusion Exacerbation of pre-existing clinical symptoms, formation of new lesions, or cavitation of prior pulmonary infiltrates is known as tuberculosis IRIS or paradoxical reaction. Despite the clinical and radiological exacerbation, mycobacterial cultures usually stay negative. Continuation of anti-TB medications and high-dose corticosteroids are the backbone of treatment but in refractory cases, immune modulation is needed with anti-TNF-α agents. Disclosures All Authors: No reported disclosures


Infliximab for Immune Reconstitution Inflammatory Syndrome (IRIS) in Tuberculous Meningitis; A Treatment Paradox
Background. Tumor necrosis factor (TNF)-α inhibitors are known for the reactivation of latent tuberculosis (TB). As a paradox, it has been reported to have a role in the treatment of immune reconstitution inflammatory syndrome (IRIS) from anti-TB therapy.
Methods. We report a case of paradoxical worsening of central nervous system TB after initiation of anti-TB medications, which was treated successfully with infliximab (TNF-α inhibitor).

Results.
A 34-year-old man from Nepal with a history of untreated latent TB presented with complaints of occipital headache, slurred speech, and witnessed seizure. His physical exam was consistent with hyperreflexia. MRI of the brain revealed multiple small contrast-enhancing lesions in cerebral hemispheres. CT Chest showed bilateral centrilobular nodules suggestive of miliary TB. Cerebrospinal fluid (CSF) analysis showed pleocytosis, high protein, and low glucose. He was started on isoniazid, rifampin, ethambutol, and pyrazinamide along with high-dose dexamethasone for TB meningitis. Later, MTB DNA probe from bronchioalveolar lavage and CSF detected Mycobacterium Tuberculosis which was pan-susceptible. Repeat MRI of the brain 6 months into therapy revealed worsening of brain lesions. Moxifloxacin and linezolid were added to the regimen given clinical progression on first-line therapy. 6-months into this enhanced regimen he started experiencing blurring of vision. Visual field mapping showed left homonymous hemianopia. Repeat MRI of the brain confirmed extensive changes of basilar meningitis completely enveloping the optic chiasm. IRIS from TB was suspected. His prednisone dose was increased, and 3-doses of infliximab infusion were, 2-weeks apart were administered which showed clinical and radiological improvement. MRI Brain MRI Brain (axial T2/flair sequence) shows hyperintensities in multiple locations including the involvement of the left optic nerve and the left occipital region.
Conclusion. Exacerbation of pre-existing clinical symptoms, formation of new lesions, or cavitation of prior pulmonary infiltrates is known as tuberculosis IRIS or paradoxical reaction. Despite the clinical and radiological exacerbation, mycobacterial cultures usually stay negative. Continuation of anti-TB medications and high-dose corticosteroids are the backbone of treatment but in refractory cases, immune modulation is needed with anti-TNF-α agents. Background. Non-Tuberculous Mycobacteria (NTM) cause infections in immunocompetent as well as immunocompromised individuals affecting pulmonary and extra pulmonary sites. These pathogens are widely distributed globally and recent reports have shown their rise in many developed countries. Our study aimed to assess the disease magnitude, describe patient characteristics and risk factors, assess diagnostic and therapeutic measures and review outcomes furthering our understanding of the overall disease process.

NTM Infections; A Rising Global Health Problem/Clinical Characteristics and Outcomes of Patients with Non-Tuberculous Mycobacterial Infections at Two Tertiary Academic Medical Centers
Methods. We conducted a retrospective, multicenter review of patients with positive NTM cultures treated at University Hospital System and South Texas Veterans Health Care System (STVHCS) from 2011 to 2018. Infections were classified as pulmonary or extrapulmonary, and we recorded demographics, microbiological data, treatment regimens, duration, complications, follow-up and mortality. All categorical variables were described using percentages and compared between groups using the chi-square test.
Results. A total of 176 patients were included for analysis, of which 111 (63.1%) met criteria for NTM disease (2020 ATS/IDSA). The most common cultured mycobacterium was M. Avium Complex (MAC). M. abscessus-chelonae was more commonly associated with clinical disease and isolated from an extra pulmonary site whereas M. simiae complex had similar distribution between the infected and un-infected groups. Over 50% of patients received treatment (80% in the infected group). Cure was seen in 47.2%, allcause mortality was 27% at last follow-up. Median duration of therapy was 10 months. 47% of patients experienced adverse effects which led to treatment discontinuation in one third of patients. Patients who were able to achieve a cure received a longer duration of therapy (12 vs 7 months; not statistically significant) and treatment was halted more commonly in the group that did not achieve eventual cure (42.6% vs. 16.7%, p=0.007).