Impact of Tocilizumab on Clinical Outcomes in COVID-19-Associated Cytokine Release Syndrome: A Single-Center Experience.

BACKGROUND: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. METHODS: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. RESULTS: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. CONCLUSION: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.

Safety of Nebulized Colistin Solution as Adjunctive Treatment of Lower Respiratory Tract Infections.

BACKGROUND: Systemic colistin is often utilized for management of drug resistant lower respiratory tract infections (LRTI). Nebulized administration of colistin allows direct instillation of active agent to maximize concentrations and limit systemic toxicities. Current literature supports efficacy of nebulized colistin as adjunctive treatment for LRTI. However, there is a paucity of data surrounding safety of this administration technique. METHODS: The electronic medical record (EMR) was queried to identify patients treated with nebulized colistin between January 1, 2016 and December 31, 2018. The data collected from the EMR and hospital adverse drug reaction (ADR) reporting systems included: demographics, dose, serum creatinine (SCr), concomitant nephrotoxins, infecting pathogen, treatment-emergent ADRs, and drug toxicities. The primary outcome was prevalence of renal, neurologic, or respiratory ADRs secondary to nebulized colistin. RESULTS: Thirty-two patients were administered nebulized colistin during the study period. Approximately 19% of patients had baseline chronic kidney disease. Cultures were positive in 29 patients of which 11 organisms were resistant to all tested antimicrobials. Three patients experienced acute kidney injury (AKI), 1 patient experienced a neurologic reaction, and 1 patient experienced a respiratory reaction, though none were considered treatment-related. CONCLUSION: The results of our study signify localized administration of colistin results in a low incidence of systemic adverse events. Nebulized colistin is a safe adjunct for managing LRTI.