A Randomized Controlled Trial to Evaluate the Safety and Efficacy of a Novel Inhaled Biologic Therapeutic in Adults with Respiratory Distress Secondary to COVID-19 Infection.

INTRODUCTION: Inhaled therapeutics may act to directly target and attenuate lung inflammation due to COVID-19. An inhalation form of a novel biologic drug, AMP5A, is being developed as an immunomodulatory agent to treat dysregulated immune responses and is being studied in hospitalized patients to treat respiratory complications due to COVID-19. METHODS: A randomized, controlled, phase I trial was conducted to evaluate hospitalized adults with respiratory distress secondary to COVID-19. Patients received the standard care (SOC) for COVID-19, including respiratory therapy, corticosteroids, and antiviral therapies such as remdesivir. Patients were randomized 1:1 to inhalation treatment with AMP5A as an adjunct to SOC or to SOC alone (control). AMP5A was administered via inhalation daily for 5 days via hand-held nebulizer, non-invasive ventilator, or mechanical ventilation. Safety and clinical efficacy endpoints were evaluated. RESULTS: Forty subjects were enrolled and randomized (n = 19 AMP5A, n = 21 control). Remdesivir was used in fewer AMP5A subjects (26%) than control (52%), and dexamethasone was administered for most subjects (84% AMP5A, 71% control). The study met its primary endpoint with no AMP5A treatment-related adverse events (AEs), and the incidence and severity of AEs were comparable between groups: 18 AEs for control (8 mild, 1 moderate, 9 severe) and 19 AEs for AMP5A (7 mild, 7 moderate, 5 severe). Notably, subjects treated with AMP5A had fewer deaths (5% vs. 24%), shorter hospital stay (8 days vs. 12 days), fewer ICU admissions (21% vs. 33%), and a greater proportion with improved clinical outcomes than control. CONCLUSION: The phase I clinical results indicate inhaled AMP5A is safe, is well tolerated, and could lead to fewer patients experiencing deterioration or death. Based on the treatment effect (i.e., reduced mortality), a phase II trial has been initiated. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04606784.

Sex, race, and the development of acute lung injury.

BACKGROUND: Prior studies suggest that mortality differs by sex and race in patients who develop acute lung injury (ALI). Whether differences in presentation account for these disparities remains unclear. We sought to determine whether sexual and racial differences exist in the rate of ALI development and ALI-related mortality after accounting for differences in clinical presentations. METHODS: This was a multicenter, observational cohort study of 5,201 patients at risk for ALI. Multivariable logistic regression with adjustment for center-level effects was used to adjust for potential covariates. RESULTS: The incidence of ALI development was 5.9%; in-hospital mortality was 5.0% for the entire cohort, and 24.4% for those patients who developed ALI. Men were more likely to develop ALI compared to women (6.9% vs 4.7%, P , .001) and had a nonsignificant increase in mortality when ALI developed (27.6% vs 18.5%, P 5 .08). However, after adjustment for baseline imbalances between sexes these differences were no longer significant. Black patients, compared to white patients, presented more frequently with pneumonia, sepsis, or shock and had higher severity of illness. Black patients were less likely to develop ALI than whites (4.5% vs. 6.5%, P 5 .014), and this association remained statistically significant after adjusting for differences in presentation (OR, 0.66; 95 % CI, 0.45-0.96). CONCLUSIONS: Sex and race differences exist in the clinical presentation of patients at risk of developing ALI. After accounting for differences in presentation, there was no sex difference in ALI development and outcome. Black patients were less likely to develop ALI despite increased severity of illness on presentation.

The use of a critical care consult team to identify risk for methicillin-resistant Staphylococcus aureus infection and the potential for early intervention: a pilot study.

OBJECTIVE: To test whether a critical care consult team can be used to identify patients who have methicillin-resistant Staphylococcus aureus nasal colonization during a window period at which they are at highest risk for methicillin-resistant S. aureus infection and can most benefit from topical decolonization strategies. DESIGN: Prospective cohort study. SETTING: Two adult tertiary care hospitals. PATIENTS: Patients with at least one risk factor for methicillin-resistant S. aureus nasal colonization who were seen by a critical care consult team for potential intensive care unit admission were enrolled. INTERVENTIONS: Nasal cultures for methicillin-resistant S. aureus were performed on all subjects. All subjects were followed for the development of a methicillin-resistant S. aureus infection for 60 days or until hospital discharge. Demographic and outcome data were recorded on all subjects. MEASUREMENTS AND MAIN RESULTS: Two hundred subjects were enrolled. Overall 29 of 200 (14.5%) were found to have methicillin-resistant S. aureus nasal colonization. Methicillin-resistant S. aureus infections occurred in seven of 29 (24.1%) subjects with methicillin-resistant S. aureus nasal colonization vs. one of 171 (0.6%) subjects without methicillin-resistant S. aureus nasal colonization (p < .001). Methicillin-resistant S. aureus clinical specimens were recovered in 15 of 29 (51.7%) subjects with methicillin-resistant S. aureus nasal colonization vs. two of 171 (1.2%) without methicillin-resistant S. aureus nasal colonization. CONCLUSIONS: A critical care consult team can be used to rapidly recognize patients with methicillin-resistant S. aureus nasal colonization who are at very elevated risk for methicillin-resistant S. aureus infection. The use of such a team to recognize patients who have greatest potential benefit from decolonization techniques might reduce the burden of severe methicillin-resistant S. aureus infections.

Evidence for biliary excretion of vancomycin into stool during intravenous therapy: potential implications for rectal colonization with vancomycin-resistant enterococci.

Sixty-three stool samples and five bile samples were prospectively collected from 33 patients receiving intravenous vancomycin therapy and were quantitatively analyzed for vancomycin by a competitive immunoassay. Vancomycin was excreted via bile into the stools of almost all patients at concentrations of 3.3 to 94.8 microg/ml after >/=5 days of a therapy of 1 g every 12 h.