Objectives: To identify the most efficacious timing for tocilizumab administration in critically ill patients infected with severe acute respiratory syndrome coronavirus-2. Design: Observational multicenter cohort study. Setting: A total of 23 acute care hospitals in four states. Patients: One-hundred eighteen patients admitted between March 13, 2020, and April 16, 2020. Eighty-one patients received tocilizumab, and 37 were untreated and served as a control group. Measurements and Main Results: The main outcome was mortality and was analyzed by timing of tocilizumab dosing. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered greater than 1 day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was used for comparison. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated ( p = 0.003). Dosing tocilizumab late was associated with an increased mortality compared with the untreated group ( p = 0.006). Conclusions: Early tocilizumab administration was associated with decreased mortality in critically ill severe acute respiratory syndrome coronavirus-2 patients, but a potential detriment was suggested by dosing later in a patient’s course.

No abstract

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2. We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between 3/13/20 and 4/16/20. This was a multi-center study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. In the absence of mechanical ventilation, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were male, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% expired, of which 43.9% were African American. Mechanical ventilation was required in 55.9%, of which 34.5% expired. Avoidance of MV (p value = 0.002) and increased survival (p value < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill COVID-19 patients.

Background Eravacycline is a novel fluorocycline approved for treatment of intraabdominal infections, with a broad spectrum of activity against a range of pathogens including multidrug-resistant species, including ESBL- or KPC-producing isolates. It is approved for twice-daily dosing with no need for adjustment in renal dysfunction. In the concomitant administration with CYP 3A4-inducing drugs, eravacycline dosing should be modified. Objective To evaluate the efficacy and safety of eravacycline in a range of infections such as intraabdominal infections, pneumonia and diabetic foot infections in seriously ill patients. Methods A retrospective observational cohort study using electronic patient records of 50 consecutive patients administered eravacycline during inpatient acute care admission or as part of outpatient antibiotic therapy (OPAT). Results Therapy of 1.5 mg/kg q24h was initiated in the hospital in most patients, although some of the less sick were managed in the office or OPAT setting. All patients concluded their management outside of the hospital. Of the 50 patients, 47 (94%) achieved clinical resolution of their infection and 3 (6%) clinical failures occurred. Only three (6%) patients did not have comorbidities, three had a single comorbidity (6%), and the majority (88%) of patients had two or more comorbidities. Most common infections were intraabdominal (36%), pneumonia (18%), diabetic foot (12%), spontaneous bacterial peritonitis (8%) and empyema (8%). Almost half of infections had more than one pathogen isolated, and resistant isolates were frequent. The drug was well tolerated with only two reports of nausea, which did not result in treatment discontinuation, and in 30 days of post-eravacycline therapy only one case of Clostridiodes difficile . Conclusions In this real-world setting, eravacycline demonstrated a similar high level of clinical efficacy as seen in clinical trials, 94%, in a variety of infections, including against multidrug-resistant bacteria, and was well tolerated.