Early Tocilizumab Dosing Is Associated With Improved Survival in Critically Ill Patients Infected With Severe Acute Respiratory Syndrome Coronavirus-2.

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.

Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2.

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter 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 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, 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 men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 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 patients with coronavirus disease 2019) COVID-19).

Treatment of Acute Osteomyelitis with Once-Weekly Oritavancin: A Two-Year, Multicenter, Retrospective Study.

BACKGROUND: Acute osteomyelitis is typically caused by Gram-positive pathogens, commonly antibiotic-resistant Staphylococcus species. Standard antibiotic treatment is challenging due to required multiple daily doses, therapeutic drug monitoring, and parenteral administration for at least 4 weeks. Oritavancin is a long-acting lipoglycopeptide antibiotic approved as a single 1200 mg dose for the treatment of adult patients with acute bacterial skin and skin structure infections. OBJECTIVE: To characterize the real-world use, efficacy, and safety of oritavancin in adult patients with acute osteomyelitis. METHODS: This was a 2-year, multicenter, retrospective, descriptive study of patients treated for acute osteomyelitis with weekly doses of oritavancin. End of therapy evaluation (ETE) was defined as evaluation at 7-10 days after the last dose of oritavancin, and post-therapy assessment (PTE) was at 3 months and 6 months. At ETE and PTE, patients were interviewed via telephone for clinical outcomes, using a standard questionnaire. Electronic medical record review was also conducted. RESULTS: 134 patients were treated with oritavancin for acute osteomyelitis across 20 different Metro Infectious Disease Consultants infusion centers in six states. Of total positive cultures, 71.9% (92/128) were methicillin-resistant Staphylococcus aureus (MRSA) from deep wounds, bone, or joint culture; an additional nine (6.7%) of 134 patients presented with concomitant MRSA bacteremia. Oritavancin was administered via intravenous catheter; patients received an initial treatment of 1200 mg and then 800 mg weekly thereafter for a total number of doses of four (n = 118) or five (n = 16). 118 patients (88.1%) of the baseline 134 patients achieved clinical success at the ETE timepoint. 130 patients were available for PTE at 3 months and 6 months. Overall, relapse or persistent infection was diagnosed in 13/134 (9.7%) patients. Nine (6.7%) of 134 patients were admitted to the hospital during the follow-up period but none for osteomyelitis. Adverse events were reported in five (3.7%) patients including hypoglycemia-related symptoms (three patients), tachycardia (one patient), and tachycardia with chest pain (one patient). None of these patients were hospitalized due to adverse events, and all patients eventually finished their treatment regimens. CONCLUSION: This is the largest real-world clinical study of adult patients treated with oritavancin for acute osteomyelitis. Use of oritavancin for acute osteomyelitis infection resulted in a high rate of positive clinical outcomes and a low incidence of adverse events, thereby providing potential for a convenient, effective, and safe therapeutic option. Future prospective and comparative studies are needed to validate these findings.

A Real-World Assessment of Clinical Outcomes and Safety of Eravacycline: A Novel Fluorocycline.

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.