Antibiotic stewardship to reduce inappropriate antibiotic prescribing in integrated academic health-system urgent care clinics.

OBJECTIVE: To develop and implement antibiotic stewardship activities in urgent care targeting non-antibiotic-appropriate acute respiratory tract infections (ARIs) that also reduces overall antibiotic prescribing and maintains patient satisfaction. PATIENTS AND SETTING: Patients and clinicians at the urgent care clinics of an integrated academic health system. INTERVENTION AND METHODS: The stewardship activities started in fiscal 2020 and included measure development, comparative feedback, and clinician and patient education. We measured antibiotic prescribing in fiscal years 2019, 2020, and 2021 for the stewardship targets, potential diagnosis-shifting visits, and overall. We also collected patient satisfaction data for ARI visits. RESULTS: From FY19 to FY21, 576,609 patients made 1,358,816 visits to 17 urgent care clinics, including 105,781 visits for which stewardship measures were applied and 149,691 visits for which diagnosis shifting measures were applied. The antibiotic prescribing rate decreased for stewardship-measure visits from 34% in FY19 to 12% in FY21 (absolute change, -22%; 95% confidence interval [CI], -23% to -22%). The antibiotic prescribing rate decreased for diagnosis-shifting visits from 63% to 35% (-28%; 95% CI, -28% to -27%), and the antibiotic prescribing rate decreased overall from 30% to 10% (-20%; 95% CI, -20% to -20%). The patient satisfaction rate increased from 83% in FY19 to 89% in FY20 and FY21. There was no significant association between antibiotic prescribing rates of individual clinicians and ARI visit patient satisfaction. CONCLUSIONS: Although it was affected by the COVID-19 pandemic, an ambulatory antimicrobial stewardship program that focused on improving non-antibiotic-appropriate ARI prescribing was associated with decreased prescribing for (1) the stewardship target, (2) a diagnosis shifting measure, and (3) overall antibiotic prescribing. Patient satisfaction at ARI visits increased over time and was not associated with clinicians' antibiotic prescribing rates.

Antiviral Drug Discovery for the Treatment of COVID-19 Infections.

The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recently emerged human coronavirus. COVID-19 vaccines have proven to be successful in protecting the vaccinated from infection, reducing the severity of disease, and deterring the transmission of infection. However, COVID-19 vaccination faces many challenges, such as the decline in vaccine-induced immunity over time, and the decrease in potency against some SARS-CoV-2 variants including the recently emerged Omicron variant, resulting in breakthrough infections. The challenges that COVID-19 vaccination is facing highlight the importance of the discovery of antivirals to serve as another means to tackle the pandemic. To date, neutralizing antibodies that block viral entry by targeting the viral spike protein make up the largest class of antivirals that has received US FDA emergency use authorization (EUA) for COVID-19 treatment. In addition to the spike protein, other key targets for the discovery of direct-acting antivirals include viral enzymes that are essential for SARS-CoV-2 replication, such as RNA-dependent RNA polymerase and proteases, as judged by US FDA approval for remdesivir, and EUA for Paxlovid (nirmatrelvir + ritonavir) for treating COVID-19 infections. This review presents an overview of the current status and future direction of antiviral drug discovery for treating SARS-CoV-2 infections, covering important antiviral targets such as the viral spike protein, non-structural protein (nsp) 3 papain-like protease, nsp5 main protease, and the nsp12/nsp7/nsp8 RNA-dependent RNA polymerase complex.

Biomarkers for the clinical development of antiviral therapies.

With the morbidity and mortality associated with the COVID-19 pandemic that we are witnessing this year, the risks posed by emerging viral diseases to global health are all too obvious. This pandemic highlights the importance of antiviral drug discovery, which targets emerging viral pathogens, as well as existing pathogenic viruses that undergo continuous evolution. Drug discovery and development is a long and resource intensive process; however, the use of biomarkers can accelerate clinical development of antivirals by providing information regarding diagnosis of specific viral infections, status of infection, potential safety parameters, and antiviral responses. In clinical practice, many of the biomarkers initially utilized to support clinical development are also used for patient care. While viral load is a standard and essential biomarker used to detect the desired viral suppression induced by an antiviral agent, it has become apparent that additional biomarkers, whether related to the virus, the host or as a consequence of the drug's mechanistic effects, are also important for monitoring clinical outcomes associated with an antiviral therapy. This review summarizes the biomarkers used in the clinical development (as well as in clinical practice, where appropriate) of antiviral therapies for hepatitis C virus, hepatitis B virus, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus 2.