Real-world evaluation of the impact of two anti-SARS-CoV-2 monoclonal antibody regimens on COVID-19 hospitalizations in older adults.

Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce coronavirus disease 2019 (COVID-19)-related hospitalizations. The purpose of this study was to assess the real-world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older. This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within 10 days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit. A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (odds ratio: 0.20 [95% CI: 0.07-0.59]). There were zero intubations and zero deaths compared to 3 (2.2%) and 2 (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%). Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age.

Medication safety in a pandemic: A multicentre point prevalence study of QTc monitoring of hydroxychloroquine for COVID-19.

WHAT IS KNOWN AND OBJECTIVE: A pandemic can strain all aspects of the healthcare system, including the ability to monitor the safety of medication use. Reviewing the adequacy of medication safety practices during the COVID-19 pandemic is critical to informing responses to future pandemics. The purpose of this study was to evaluate medication safety practices at a height of both COVID-19 cases and hydroxychloroquine use. METHODS: This was a multicentre observational point prevalence study. Adult inpatients receiving hydroxychloroquine for COVID-19 between March 22 and 28, 2020 were included. The primary outcome was the percentage of patients receiving appropriate QTc monitoring. Secondary outcomes included QTc prolongation, early discontinuation of hydroxychloroquine and ventricular arrhythmias. RESULTS AND DISCUSSION: A total of 59% (167/284) of patients treated with hydroxychloroquine received appropriate QTc monitoring. QTc prolongation occurred in 25%. Hydroxychloroquine was prematurely discontinued in 1.4% of patients, all due to QTc prolongation. Ventricular arrhythmia occurred in 1.1%. WHAT IS NEW AND CONCLUSION: Medication safety practices were suboptimal with regard to hydroxychloroquine monitoring at the height of the COVID-19 pandemic. Preparation for future pandemics should devote considerable attention to medication safety.

Beta-lactam comprehensive allergy management program in a community medical center.

Objective: The Beta-lactam Comprehensive Allergy Management Program (CAMP) was implemented to facilitate complete beta-lactam allergy history documentation in the electronic medical record (EMR) and increase beta-lactam utilization. The study objective was to assess the rate of complete allergy histories and days of antimicrobial therapy (DOT) before versus after CAMP implementation. Design: Quasi-experimental study with interrupted time-series analysis. Setting: Non-teaching, urban, and community medical center within a multi-hospital health system. Patients: Adult inpatients with a beta-lactam allergy receiving antimicrobial therapy. Methods: The multidisciplinary CAMP team screened, interviewed, and collected allergy history details of adult inpatients with a beta-lactam allergy receiving antimicrobial therapy starting January 4, 2021. Patients were stratified as high, moderate, or low risk of IgE-mediated allergy and referred to an allergist for skin testing or drug challenge. The EMR was updated with interview details and drug challenge or skin test results. The primary endpoint was rate of complete allergy history documentation before (12/1/18-4/1/19) compared to after (1/4/21-5/1/21) program implementation. The secondary endpoint was days of inpatient beta-lactam therapy. Implementation logistics, de-labeling rate, and antimicrobial therapy changes were evaluated. Results: The program evaluated 392 individuals, with 184 and 208 patients comprising the pre- and post-intervention groups, respectively. The post-intervention period was associated with an increase of 19.8% in complete allergy histories (0.359 PPc; R 2 0.26; p = 0.002) and 9.34 beta-lactam DOT per 1,000-days-present (1.106 PPc; R 2 0.194; p = 0.009). Conclusion: Implementation of a comprehensive beta-lactam allergy management program was associated with higher rates of complete beta-lactam allergy history and beta-lactam use.

Intravenous N-Acetylcysteine in Management of COVID-19: A Case Series.

A novel coronavirus, severe acute respiratory syndrome coronavirus-2, was isolated from patients' lower respiratory tracts in December 2019. As of May 19, 2021, there were over 33 million reported infections and almost 600,000 deaths in the United States. The infection, coronavirus disease-19 (COVID-19), can lead to cytokine storm, with elevations in interleukin-6 (IL-6), IL-10, tumor necrosis factor-α, nuclear factor-kappaB (NF-kappaB), and glutathione reductase. NF-kappaB activation is necessary for further transcription of other pro-inflammatory markers. Glutathione may play a role in modulation of NF-kappaB activation and elevated glutathione reductase may indicate glutathione depletion. Administration of N-acetylcysteine (NAC) may replenish spent glutathione and attenuate over-activation of NF-kappaB. This retrospective case series included 10 patients who were COVID-19 positive and received intravenous NAC in an attempt to attenuate the cytokine storm. Patients' outcomes were graded based on the World Health Organization symptom severity scale from 0, no evidence of infection, to 8, death. Overall, the median WHO Scale prior to NAC was 6.5, and increased by day seven, which indicated clinical worsening. This retrospective case series showed no benefit of NAC; however, further studies are needed to elucidate if differences in drug regimens would lead to positive results.

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.

Early clinical outcomes with tocilizumab for severe COVID-19: a two-centre retrospective study.

Severe COVID-19 (coronavirus disease 2019) is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an interleukin-6 (IL-6) inhibitor effective in treating CRS secondary to chimeric antigen receptor T-cell (CAR T-cell) therapy. The efficacy of tocilizumab in treating COVID-19 is unknown. This was a retrospective cohort study conducted at two hospitals in northern New Jersey (USA). All patients treated with tocilizumab for confirmed or suspected COVID-19 between 10 March 2020 and 9 April 2020 at the study sites were included. The primary endpoint was clinical improvement on Day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not. A total of 45 severe and critically ill patients treated with tocilizumab for COVID-19 were evaluated. Of the 45 patients, 11 (24.4%), 22 (48.9%) and 12 (26.7%) patients improved, had no change or worsened by Day 7 after treatment, respectively. Lower white blood cell count and lactate dehydrogenase at the time of drug administration as well as shorter time from supplemental oxygen initiation to dosing were significantly associated with clinical improvement in the univariate analysis. In conclusion, tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with COVID-19.

Selective antibiotic susceptibility reporting and broad-spectrum intravenous antibiotic use: A multicentre ecological study.

Recent estimates of inpatient antibiotic use in the USA suggest that broad-spectrum antibiotic use has increased significantly. The objective of this study was to assess the impact of a selective antibiotic susceptibility reporting intervention on broad-spectrum intravenous (i.v.) antibiotic use in seven hospitals of a health system in New Jersey. This was a retrospective pre- and post-intervention ecological study. Standardised selective antibiotic susceptibility reporting rules were developed and implemented between January 2016 and June 2017. The 8 months before and after each individual hospital's implementation constituted the pre- and post-intervention study periods. The primary outcome was the rate of broad-spectrum i.v. antibiotic use for hospital-onset/multidrug-resistant infections (broad MDR). Secondary outcome measures were the use rates of non-glycopeptide anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agents, carbapenems, non-carbapenem antipseudomonal ß-lactams, third-generation cephalosporins, first/second-generation cephalosporins, fluoroquinolones and narrow-spectrum penicillins. Antibiotic use data were collected as inpatient i.v. antibiotic days of therapy per 1000 patient days (DOT/1000-PD). Interrupted time series analysis with segmented regression was used to compare outcomes. There was no significant change in the use of broad MDR agents (slope change, +0.54 DOT/1000-PD per month, 95% confidence interval -1.78 to 2.87) or other antibiotic classes. Whilst the implementation of selective antibiotic susceptibility reporting across seven hospitals had no impact on overall broad-spectrum i.v. antibiotic use, further study is needed to determine the long-term impact of this intervention.