Objective: To review available evidence on corticosteroids in acute respiratory distress syndrome (ARDS), Coronavirus Disease 2019 (COVID-19), and other viral pneumonias. Data Sources: A literature search of MEDLINE, PubMed and clinicaltrials.gov was performed to identify studies between 1980 to 2020 using the following search terms: corticosteroids, COVID19, severe respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and influenza. Pre-printed articles were also reviewed at medRxiv.org . Data Analysis: Corticosteroids were not recommended early in the COVID-19 pandemic outside of the use for concomitant indications (i.e. ARDS, septic shock) as they have been associated with delayed time to viral clearance in other viral pneumonias. A randomized trial showed a mortality benefit with dexamethasone in COVID-19. Guidelines have been updated to include a strong recommendation for their use in COVID-19 in those hospitalized requiring supplemental oxygen or mechanical ventilation. Conclusion: Based on data from available randomized trials, patients that require respiratory support or mechanical ventilation benefit from corticosteroid therapy. Corticosteroids are an inexpensive and readily available therapy that should be standard of care in hospitalized COVID-19 patients requiring respiratory support.

Background Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen’s intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population. Methods This was a single center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010 to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid versus linezolid. We also described non-hematological adverse drug events (ADEs) and therapy discontinuation rates. In exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least four weeks. Results Twenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid versus linezolid on platelet counts, absolute neutrophil counts (ANC), and hemoglobin over seven weeks using mixed-effects ANOVA models. ANC was significantly decreased in both groups after seven weeks of therapy (p=0.04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and two of three (67%) patients were cured or clinically cured with tedizolid and linezolid-containing regimens, respectively. Conclusions This study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients.

Background Mycobacterium abscessus complex is a rapidly growing mycobacteria notoriously refractory to therapy due to inherent antimicrobial resistance mechanisms. Tedizolid is an oxazolidinone with in vitro activity against many nontuberculous mycobacteria species, including M. abscessus complex. This study describes the clinical outcomes of solid organ transplant (SOT) recipients with M. abscessus complex infection treated with tedizolid at a single medical center. Methods This retrospective cohort study included adult SOT recipients who met the ATS/IDSA criteria for nontuberculous mycobacterial infection and were treated with a multi-drug regimen that included tedizolid for at least four weeks between January 1, 2010 to August 31, 2019. Symptomatic improvement was defined as either decreased cough or sputum production for pulmonary infection and decrease in size of the primary lesion for skin or surgical site infection. The criteria for a microbiologic response was more than one negative culture with the causative species and sustained until the end of treatment. Clinical cure was defined as improvement of symptoms without proven negative cultures during and sustained until the end of treatment. A patient was considered cured if both symptomatic (if applicable) and microbiologic criteria were fulfilled. The clinical outcomes were compared from the initiation of tedizolid-containing regimen to the end of any M. abscessus complex treatment. Results Twelve patients were included. Mycobacterium abscessus abscessus (7/12, 58%) was the most common subspecies. The distribution of infections were as follows: five (42%) disseminated infections, five (42%) pulmonary infections, five (42%) surgical site infections, and four (33%) skin and soft tissue infections. Six patients were cured or clinically cured for all sites of infection (50%), three patients died (25%), and one patient had two recurrences (Table 1). Table 1. Patient demographics and outcomes of M. abscessus complex infection. Conclusion Most patients had multiple sites of infection, and treatment required combination antimicrobial therapy and appropriate surgical management. In this small cohort, tedizolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement in SOT recipients with M. abscessus complex infection. Disclosures All Authors: No reported disclosures

Background Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the long-term tolerability of antimicrobials. The oxazolidinones, linezolid and tedizolid, display in vitro activity against many NTM species and demonstrate excellent oral bioavailability. This study compares the hematologic safety profile of linezolid versus tedizolid for the treatment of NTM in solid organ transplant (SOT) recipients. Methods This retrospective cohort study included adult SOT recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat NTM between January 1, 2010 to August 31, 2019. The primary endpoint was the hematologic effects of linezolid versus tedizolid from therapy initiation to week seven. This time frame was chosen based on the median duration of therapy. A mixed-effects ANOVA model was used to assess the effects of linezolid and tedizolid on platelet counts (PLT), absolute neutrophil counts (ANC), and hemoglobin (Hgb) across time. Subjects were treated as a random effect. The secondary analysis described the proportion of adverse effects and discontinuation. Results Twenty-four patients were included in the analysis (9 linezolid, 15 tedizolid). Mycobacterium abscessus abscessus was the most common isolate, and pulmonary was the most common site of infection (Table 1). The median duration of therapy was 24 days (range 3 to 164 days) and 48 days (range 11 to 571 days) for linezolid and tedizolid, respectively. All patients in the linezolid group received 600 mg daily or less for the majority of treatment duration. In the mixed-effects ANOVA, the ANC decreased in both groups after seven weeks of therapy (p=0.04). Otherwise, no significant effects for week, treatment group, or interaction between week and treatment group were found (Figure 1). Thrombocytopenia and neutropenia were common in both groups, and around one-fifth of patients in each group discontinued the medication due to adverse effects (Table 2). Table 1. Baseline characteristics of solid organ transplant recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat nontuberculous mycobacteria infections between January 1, 2010 to August 31, 2019 at UT Southwestern Medical Center. Table 2. Adverse drug events and discontinuation of therapy over seven weeks of therapy. Figure 1. Effects of linezolid versus tedizolid during the initial seven weeks of therapy using a mixed-effects ANOVA model, (a) platelet counts, (b) absolute neutrophil counts, and (c) hemoglobin. Conclusion Non-significant statistical differences were found comparing the effects of linezolid versus tedizolid for PLT, ANC, and Hgb using mixed-effects ANOVA models. Larger cohort studies are required to compare the hematologic adverse effect profile of the oxazolidinones for the treatment of NTM infections in SOT recipients. Disclosures All Authors: No reported disclosures