Citations

Abstract Objectives Despite low rates of bacterial coinfection in patients admitted with COVID-19, antimicrobials are frequently prescribed. Our primary objective was to evaluate antimicrobial prescribing over time in patients admitted with COVID-19. The secondary objectives were to evaluate the role of ID providers in antimicrobial utilization, describe the rate of confirmed bacterial infection and determine factors associated with empirical antimicrobial prescribing in COVID-19. Materials and methods Retrospective review was performed for adult patients admitted to a tertiary care centre with COVID-19 between 1 March 2020 and 30 November 2020. Patient demographics, disease severity, risk factors for severe disease, clinical outcomes, antimicrobial prescribing and respiratory microbiological testing were collected and analysed. Prescribing trends were evaluated by month, and factors contributing to prescribing were established using univariate and multivariable analysis. Results Antibiotics were prescribed during admission in 37.9% of the study cohort, with 85.1% of patients who received antibiotics having therapy initiated within 48 h of admission. Antibiotic prescribing incidence increased with disease. Over the study period, antimicrobial prescribing rates decreased by 8.7% per month. Multivariable analysis found ICU admission, obtainment of procalcitonin values, intubation, heart failure, haemodialysis and nursing home residence were associated with empirical antimicrobial prescribing. Conclusions Unnecessary antimicrobial prescribing in patients with viral syndromes like COVID-19 continues to represent an area of concern. Antimicrobial stewardship efforts during COVID-19 should consider patient-specific factors associated with antibiotic prescribing. Recognition of such factors, in combination with application of well-established antimicrobial stewardship tactics, may serve to impact antimicrobial prescribing trends, even as patient volumes rise.

Background: Blastomycosis can cause severe disease with progressive respiratory failure and dissemination even in immunocompetent individuals. We sought to evaluate risk factors for severe disease and mortality using clinical and laboratory data within a large health system in an endemic area. Methods: We performed a retrospective cohort study of patients diagnosed with blastomycosis at all Mayo Clinic sites from 1 January 2004 through 31 March 2020. Diagnosis was established by culture, histopathology/cytopathology, serology, antigen testing, or PCR. Disease was categorized as mild for patients treated in the outpatient setting, moderate for hospitalized patients who did not require intensive care, and severe for patients admitted to the intensive care unit. Logistic regression was used to evaluate risk factors for severe disease. A Cox proportional hazards model was constructed to evaluate mortality. Findings: We identified 210 patients diagnosed with blastomycosis. Mean age was 51 years (range, 6–84). Most subjects were male (71.0%). Extrapulmonary disease was confirmed in 24.8%. In this cohort, 40.5% of patients had mild disease, 37.6% had moderate disease, and 21.9% had severe disease. Independent risk factors for severe disease were neutrophilia (odds ratio (OR) 3.35 (95% CI 1.53–7.35), p = 0.002) and lymphopenia (OR 3.34 (95% CI 1.59–7.03), p = 0.001). Mortality at 90 days was 11.9%. Median time from diagnosis to death was 23 days (interquartile range 8–31 days). Independent risk factors for mortality were age (OR 1.04 (95% CI 1.01–1.08), p = 0.009), neutrophilia (OR 2.84 (95% CI 1.04–7.76), p = 0.041), and lymphopenia (OR 4.50 (95% CI 1.67–12.11), p = 0.003). Blastomyces immunodiffusion had an overall sensitivity of 39.6% (95% CI 30.1–49.8). Sensitivity was higher among those who were tested 4 weeks or longer after the onset of symptoms. Urine Blastomyces antigen had a significantly higher sensitivity of 80.8% (95% CI 68.1–89.2) compared to serology. There was a trend towards higher antigen concentration in patients with severe disease. The sensitivity of PCR from respiratory specimens was 67.6% (95% CI 50.1–85.5). Conclusion: In this cohort, we did not find an association between pharmacologic immunosuppression and disease severity. Lymphopenia at diagnosis was an independent risk factor for mortality. This simple marker may aid clinicians in determining disease prognosis.

Abstract Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained.

Abstract Given the urgent need for treatments during the coronavirus disease 2019 pandemic, the US Food and Drug Administration issued emergency use authorizations (EUAs) for multiple therapies. In several instances, however, these EUAs were issued before sufficient evidence of a given therapy’s efficacy and safety were available, potentially promoting ineffective or even harmful therapies and undermining the generation of definitive evidence. We describe the strengths and weaknesses of the different therapeutic EUAs issued during this pandemic. We also contrast them to the vaccine EUAs and suggest a framework and criteria for an evidence-based, trustworthy, and publicly transparent therapeutic EUA process for future pandemics.

Abstract The raging COVID-19 pandemic in India and reports of “vaccine breakthrough infections” globally have raised alarm mandating the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed over 1.3 million SARS-CoV-2 genomes from 178 countries and performed whole-genome viral sequencing from 53 COVID-19 patients, including 20 vaccine breakthrough infections. We identified 116 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a three-month window. Deletions in the Spike protein N-terminal domain (NTD) are highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 18.2, 95% CI: 7.53-48.7; p=1.465x10-18). In the recent COVID-19 surge in India, an NTD deletion (ΔF157/R158) increased over 10-fold in prevalence from February 2021 (1.1%) to April 2021 (15%). During the recent surge in Chile, an NTD deletion (Δ246-253) increased rapidly over 30-fold in prevalence from January 2021 (0.86%) to April 2021 (33%). Strikingly, these simultaneously emerging deletions associated with surges in different parts of the world both occur at an antigenic supersite that is targeted by neutralizing antibodies. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences and identified deletions within this NTD antigenic supersite in a patient with vaccine breakthrough infection (Δ156-164) and other deletions from unvaccinated severe COVID-19 patients that could represent emerging deletion-prone regions. Overall, the expanding repertoire of Spike protein deletions throughout the pandemic and their association with case surges and vaccine breakthrough infections point to antigenic minimalism as an emerging evolutionary strategy for SARS-CoV-2 to evade immune responses. This study highlights the urgent need to sequence SARS-CoV-2 genomes at a larger scale globally and to mandate a public health policy for transparent reporting of relevant clinical annotations (e.g. vaccination status) in order to aid the development of comprehensive therapeutic strategies.

Antibiotic use is often the target of interventions in health care organizations that aim to decrease healthcare-associated infections (HAI) such as Clostridioides difficile (CDI); this is particularly important for fluoroquinolones (FQ), which are frequently used in critical care settings. In this study, using a multiple case study research approach, we conduct an in-depth analysis of an intervention aimed at limiting ICU prescriber access to FQ in two ICUs of two hospitals. The data collection and analysis were guided by a human factors engineering approach based on the SEIPS (Systems Engineering Initiative for Patient Safety) model and evidence-based implementation principles. Our results show some differences in the implementation of the FQ intervention between the two ICUs, such as level and method of FQ restriction, and training and communication with physicians and pharmacists. In both ICUs, several organizational learning mechanisms helped to quickly identify problems with the intervention and ensure that changes were made in a just-in-time manner (e.g. just-in-time training, removal of FQ in order set for pneumonia). Despite their organizational differences, both sites developed strategies to successfully implement the FQ intervention.

Hospitalized patients with COVID-19 show increased serum concentrations of neurofilament light chain that correlate with worse clinical outcomes.

AbstractBackgroundBamlanivimab and casirivimab-imdevimab are authorized for emergency use treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients at high risk for developing severe disease or hospitalization. Their safety and efficacy have not been specifically evaluated in solid organ transplant recipients.MethodsWe retrospectively reviewed solid organ transplant recipients who received monoclonal antibody infusion for COVID-19 at Mayo Clinic sites through January 23, 2021. Outcomes included emergency department visit, hospitalization, mortality, and allograft rejection.ResultsSeventy-three patients were treated, most commonly with bamlanivimab (75.3%). The median age was 59 years, 63% were male, and the median Charlson comorbidity index was 5. Transplant type included 41 kidney (56.2%), 13 liver (17.8%), 11 heart (15.1%), 4 kidney-pancreas (5.5%), 2 lung (2.7%), 1 heart-liver, and 1 pancreas. Eleven (15.1%) patients had an emergency department visit within 28 days of infusion, including 9 (12.3%) who were hospitalized for a median of 4 days. One patient required intensive care unit admission for a nonrespiratory complication. No patients required mechanical ventilation, died, or experienced rejection. Ten adverse events occurred, with 1 seeking medical evaluation. Hypertension was associated with hospital admission (P < .05), while other baseline characteristics were similar. The median time from symptom onset to antibody administration was 4 days in nonhospitalized patients compared with 6 days among hospitalized patients (P < .05).ConclusionsMonoclonal antibody treatment has favorable outcomes with minimal adverse effects in solid organ transplant recipients with mild to moderate COVID-19. Earlier administration of monoclonal antibody therapy appears to be more efficacious.