1402. NTM Infections; A Rising Global Health Problem/Clinical Characteristics and Outcomes of Patients with Non-Tuberculous Mycobacterial Infections at Two Tertiary Academic Medical Centers

Abstract 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. 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%, all-cause 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). Conclusion NTM infections represent a therapeutic challenge with low cure rates and high mortality. An understanding of the risk factors, treatment options and outcomes is essential to guide appropriate management. Our study highlights high rates of adverse effects and discontinuation which precludes prolonged courses of therapy required to achieve cure. Disclosures All Authors: No reported disclosures


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. 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.
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).

S786 • OFID 2021:8 (Suppl 1) • Abstracts
Conclusion. NTM infections represent a therapeutic challenge with low cure rates and high mortality. An understanding of the risk factors, treatment options and outcomes is essential to guide appropriate management. Our study highlights high rates of adverse effects and discontinuation which precludes prolonged courses of therapy required to achieve cure.
Disclosures. Background. Osteoarticular tuberculosis remains a common disease among which the spine is the most affected site. Less frequently, sacroiliac joint is involved. Its diagnosis is often delayed due to misleading and varied symptoms. The aim of this work was to study the clinical features and the contribution of imaging results in the diagnosis of tuberculous sacroiliitis.
Methods. We conducted a retrospective study including all patients hospitalized in the infectious disease department for tuberculous sacroiliitis. The diagnosis was based on clinical, laboratory and radiological features.
Conclusion. Because of its deep localization, the diagnosis of tuberculous sacroiliitis is mainly based on imaging results associated with epidemiological, clinical and laboratory features. Antitubercular therapy initiated promptly leads to recovery.

Background. Tuberculosis is a health problem in Morocco, which is increasingly indicative of human immunodeficiency virus (HIV) infection.
Objective. To determine the epidemiological, clinical and paraclinical, therapeutic and evolutionary aspects of tuberculosis and HIV co-infection.
Methods. we report 135 cases co-infected with HIV and tuberculosis, collected by the infectious diseases department at the Mohammed VI University Hospital in Marrakech. This is a 12-year retrospective study (2007 to 2020) that involved all HIVinfected patients hospitalized for tuberculosis regardless of its location.
Results. The mean age of the patients was 40 years (17-73 years). A male predominance was noted in 69% of cases. In 74.6% of cases, tuberculosis was indicative of HIV infection. Nine patients were receiving antiretroviral (ARV) treatment at the time of the discovery of tuberculosis. There were 24% pulmonary tuberculosis, 25.3% extrapulmonary tuberculosis and 49% disseminated tuberculosis. Tuberculosis was confirmed in 31.7% of cases. At the time of tuberculosis diagnosis, the average CD4 count was 86 cells / mm. Quadruple therapy with isoniazid, rifampicin, pyrazinamide and ethambutol was started in 83% of patients. The average time to start ARVs was 7 weeks. All patients who received ARVs received a combination therapy comprising the combination of 2 nucleoside analogs and one non-nucleoside analog. At the end of our work, the evolution was favorable in 53% of cases, death occurred in 25% of cases, 18.6% of patients were lost to follow-up, two cases of failure and another of relapse. Immune restoration syndrome was noted in 8 cases. Drug toxicity was observed in 24.5% of patients, 73% of which was related to hepato-toxicity of antibacillary drugs.
Conclusion. Tuberculosis is the most common opportunistic infection in people with HIV. Despite the advent of highly active triple therapy, tuberculosis is still a major cause of death in HIV positive people.
Methods. Patients with pathologically confirmed and clinically diagnosed ATB in Peking Union Medical College Hospital and Beijing Chest Hospital from April 2020 to May 2021 were enrolled as case group, while patients with LTBI in the same period were enrolled as control group. The FluoroSpot assay was used to simultaneously detect the secretion of IFN-γ, IL-2 and TNF-α in T cells stimulated by the MTB specific antigens ESAT-6 and CFP-10 at the single-cell level. A binary logistic regression model was used to fit the combined diagnostic parameters, and the sensitivity, specificity, predictive value and likelihood ratio of the differential diagnosis of ATB and LTBI were calculated. Figure 1. Schematic diagram of FluoroSpot (IFN-γ/IL-2/TNF-α) detecting cytokine-secreting specific T cells after stimulation with MTB specific antigen. A. The green spots are the total IFN-γ-secreting T cells; B. The red spots are the total IL-2secreting T cells; C. The blue spots are the total TNF-α-secreting T cells; D. The green spots are the single IFN-γ-secreting T cells; the red spots are the single IL-2-secreting T cells; the blue spots are the single TNF-α-secreting T cells; the yellow spots are the dual IFN-γ/IL-2-secreting T cells; the cyan spots are the dual IFN-γ/TNF-α-secreting T cells; the purple spots are the dual IL-2/TNF-α-secreting T cells; the white spots are the triple IFN-γ/IL-2/TNF-α-secreting T cells.