Evaluation of severe acute respiratory syndrome coronavirus 2 monoclonal antibodies in high-risk solid organ transplant recipients across three major coronavirus disease 2019 variant waves.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to impact immunocompromised populations including solid organ transplant recipients (SOTRs). Monoclonal antibodies (mAbs) have shown effectiveness in reducing COVID-19-related hospitalizations and emergency department (ED) visits in SOTRs at different time frames in the COVID-19 pandemic; however, less data exist on the impact of mAbs for SOTRs across variant waves and with the advent of available COVID-19 vaccines. METHODS: This retrospective study included SOTR outpatients who tested positive for SARS-CoV-2 and received mAbs from December 2020 to February 2022 (n = 233); using in-house sequencing of clinical samples, we monitored the emergence of Alpha, Delta, and Omicron variants. The primary outcome was a composite of 29-day COVID-19-related hospitalizations and ED visits. Prespecified secondary outcomes included individual components of the primary endpoint; for patients requiring hospitalization post-mAb administration, we describe their inpatient treatment. RESULTS: A low percentage of SOTRs treated with mAb required hospitalization or an ED visit (14.6% overall); this did not differ across COVID-19 variants (p = .152). Hospitalization and ED visits did not significantly differ between abdominal and cardiothoracic SOTRs. For hospitalized patients, the majority received treatment with corticosteroids and few required intensive care unit (ICU) care. CONCLUSION: Among SOTR outpatients with mild or moderate COVID-19 symptoms, early administration of mAb minimizes the need for hospital care. For patients requiring hospitalization, corticosteroids were common but patients experienced low rates of oxygen supplementation and ICU care. Use of mAbs in SOTRs should be considered early in the disease when therapy is available.

Real-world effectiveness of early remdesivir and sotrovimab in the highest-risk COVID-19 outpatients during the Omicron surge.

BACKGROUND: Remdesivir and sotrovimab both have clinical trial data in the outpatient setting demonstrating reduction in the risk of hospitalizations and emergency department (ED) visits related to COVID-19. OBJECTIVES: To evaluate the effectiveness of remdesivir in comparison with sotrovimab and matched high-risk control patients in preventing COVID-19-related hospitalizations and ED visits during the Omicron B.1.1.529 surge. PATIENTS AND METHODS: This retrospective cohort study included outpatients positive for SARS-CoV-2, with non-severe symptoms for ≤7 days and deemed high-risk for severe COVID-19 by an internal scoring matrix. Patients who received remdesivir or sotrovimab from 27/12/2021 to 04/02/2022 were included (n = 82 and n = 88, respectively). These were compared with a control cohort of high-risk COVID-19 outpatients who did not receive therapy (n = 90). The primary outcome was a composite of 29 day COVID-19-related hospitalizations and/or ED visits. Pre-specified secondary outcomes included components of the primary endpoint, 29 day all-cause mortality and serious adverse drug events. RESULTS: Patients treated with remdesivir were significantly less likely to be hospitalized or visit the ED within 29 days from symptom onset (11% versus 23.3%; OR = 0.41, 95% CI = 0.17-0.95). Patients receiving sotrovimab were also less likely to be hospitalized or visit the ED (8% versus 23.3%; OR = 0.28, 95% CI = 0.11-0.71). There was no difference in the incidence of hospitalizations/ED visits between sotrovimab and remdesivir. CONCLUSIONS: Our highest-risk outpatients with Omicron-related COVID-19 who received early sotrovimab or remdesivir had significantly lower likelihoods of a hospitalization and/or ED visit.

Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Infusions in High-Risk Outpatients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19-related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance. METHODS: This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA's Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (n = 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (n = 200). The primary outcome was a composite of 29-day COVID-19-related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events. RESULTS: Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14-.38]; P < .001). The mortality rate was 0% in the mAb group compared with 3.5% in the control group (P = .02). Only 2 patients receiving mAb experienced a serious adverse event requiring treatment. CONCLUSIONS: Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.

Plazomicin: A Next-Generation Aminoglycoside.

Plazomicin is a novel aminoglycoside antibiotic that binds to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis in a concentration-dependent manner. Plazomicin displays a broad spectrum of activity against aerobic gram-negative bacteria including extended-spectrum ß-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and organisms with aminoglycoside-modifying enzymes. In a large phase III clinical trial, plazomicin was shown to be noninferior to meropenem in the treatment of complicated urinary tract infections (cUTIs) with respect to the coprimary efficacy end points of the microbiologically modified intent-to-treat composite cure rate at day 5 (plazomicin 88% [168/191 subjects] vs meropenem 91.4% [180/197]) and at the test-of-cure visit (plazomicin 81.7% [156/191] vs meropenem 70.1% [138/197]). In a small phase III clinical trial, plazomicin was shown to be effective in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae. It was associated with a lower all-cause mortality or significant disease-related complication rate (23.5% [4/17]) compared with colistin (50% [10/20]). The most common adverse reactions associated with plazomicin are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension. As with other aminoglycosides, plazomicin may cause neuromuscular blockade, ototoxicity, and fetal harm in pregnant women. Due to limited efficacy and safety data, plazomicin is indicated for the treatment of cUTIs in adults with limited or no alternative treatment options, using a dosage regimen of 15 mg/kg intravenously every 24 hours for 4-7 days. Dosage reductions and therapeutic drug monitoring are warranted in patients with moderate or severe renal impairment. Plazomicin is not recommended in patients with severe renal impairment including those receiving renal replacement therapy. With the approval of plazomicin, clinicians now have an additional option for the treatment of adults with cUTIs, particularly those caused by multidrug-resistant gram-negative rods.