Implementation and outcomes of a clinician-directed intervention to improve antibiotic prescribing for acute respiratory tract infections within the Veterans' Affairs Healthcare System.

OBJECTIVE: To determine whether a clinician-directed acute respiratory tract infection (ARI) intervention was associated with improved antibiotic prescribing and patient outcomes across a large US healthcare system. DESIGN: Multicenter retrospective quasi-experimental analysis of outpatient visits with a diagnosis of uncomplicated ARI over a 7-year period. PARTICIPANTS: Outpatients with ARI diagnoses: sinusitis, pharyngitis, bronchitis, and unspecified upper respiratory tract infection (URI-NOS). Outpatients with concurrent infection or select comorbid conditions were excluded. INTERVENTION(S): Audit and feedback with peer comparison of antibiotic prescribing rates and academic detailing of clinicians with frequent ARI visits. Antimicrobial stewards and academic detailing personnel delivered the intervention; facility and clinician participation were voluntary. MEASURE(S): We calculated the probability to receive antibiotics for an ARI before and after implementation. Secondary outcomes included probability for a return clinic visits or infection-related hospitalization, before and after implementation. Intervention effects were assessed with logistic generalized estimating equation models. Facility participation was tracked, and results were stratified by quartile of facility intervention intensity. RESULTS: We reviewed 1,003,509 and 323,023 uncomplicated ARI visits before and after the implementation of the intervention, respectively. The probability to receive antibiotics for ARI decreased after implementation (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.78-0.86). Facilities with the highest quartile of intervention intensity demonstrated larger reductions in antibiotic prescribing (OR, 0.69; 95% CI, 0.59-0.80) compared to nonparticipating facilities (OR, 0.89; 95% CI, 0.73-1.09). Return visits (OR, 1.00; 95% CI, 0.94-1.07) and infection-related hospitalizations (OR, 1.21; 95% CI, 0.92-1.59) were not different before and after implementation within facilities that performed intensive implementation. CONCLUSIONS: Implementation of a nationwide ARI management intervention (ie, audit and feedback with academic detailing) was associated with improved ARI management in an intervention intensity-dependent manner. No impact on ARI-related clinical outcomes was observed.

Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

High Viral Specific Antibody Convalescent Plasma Effectively Neutralizes SARS-CoV-2 Variants of Concern.

The ongoing evolution of SARS-Co-V2 variants to omicron severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. Covid-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The FDA currently allows outpatient CCP for the immunosuppressed. Viral specific antibody levels in CCP can range ten-to hundred-fold between donors unlike the uniform viral specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-delta/pre-omicron donor units obtained before March 2021, 20 post-delta COVID-19/post-vaccination units and one pre-delta/pre-omicron hyperimmunoglobulin preparation for variant specific virus (vaccine-related isolate (WA-1), delta and omicron) neutralization correlated to Euroimmun S1 IgG antibody levels. We observed a 2-to 4-fold and 20-to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to delta or omicron, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-delta COVID-19/post-vaccination units and the hyperimmunoglobulin effectively neutralized all three variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants. Key points: All of the post-delta COVID-19/post vaccination convalescent plasma effectively neutralizes the omicron and delta variants.High-titer CCP and hyperimmunoglobulin neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.