Effect of SARS CoV2-Neutralizing Monoclonal Antibody on Hospitalization and Mortality in Long-Term Care Facility Residents.

To measure the association between intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to long-term care facility (LTCF) residents recently diagnosed with pre-symptomatic, mild-to-moderate COVID-19 and are considered high risk for disease progression with mortality, hospitalization, and adverse effects. A retrospective analysis of LTCF residents with confirmed COVID-19, pre-symptomatic, mild to moderate disease, who were treated with bamlanivimab (LY-CoV555) were compared to similar LTCF residents who did not receive monoclonal antibody treatment. Dependent variables investigated included mortality and hospitalization as primary outcomes with adverse effects as the secondary outcome. A total of 107 residents from three LTCFs were diagnosed with pre-symptomatic, mild-to-moderate COVID-19 between November 1, 2020, and December 31, 2020. Of the 107 study participants, 44 residents provided consent to treatment, of which 39 received a single intravenous infusion of neutralizing monoclonal antibody, bamlanivimab 700mg, early in the disease, and 5 received an incomplete dose. Of the 39 residents who received the full dose of bamlanivimab, 5 (12.8%) were admitted to the hospital and 4 (10.3%) died. Conversely, of the 63 residents who did not receive the monoclonal antibody, 26 (41.3 %) were admitted to the hospital and 18 (28.6%) died. Relative risk for hospitalization and death were statistically significantly lower for those residents who received the full bamlanivimab treatment. No serious adverse effects were documented on any patient. Intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to LTCF residents recently diagnosed with pre-symptomatic, mild to moderate COVID-19 was significantly associated with reduced mortality and hospitalization. The monoclonal antibody was well-tolerated.

Effect of Antimicrobial Stewardship Program Guidance on the Management of Uncomplicated Skin and Soft Tissue Infections in Hospitalized Adults.

OBJECTIVE: To assess the effect of an antimicrobial stewardship program (ASP)-bundled initiative on the appropriate use of antibiotics for uncomplicated skin and soft tissue infections (uSSTIs) at 2 academic medical centers in Pittsburgh, Pennsylvania. PATIENTS AND METHODS: A retrospective preintervention and postintervention study was conducted to compare management of patients admitted with uSSTIs before and after the implementation of the bundled initiative. The preintervention period was from August 1, 2014, through March 31, 2015, and the postintervention period was from August 1, 2015, through March 31, 2016. RESULTS: A total of 160 patients were included in the preintervention cohort, and 163 were included in the postintervention cohort. Compared with the preintervention group, the mean duration of therapy decreased (12.5 days vs 8.8 days; P<.001) and an appropriate duration of less than 10 days increased in more patients (20.6% [33 of 160] vs 68.7% [112 of 163]; P<.001) in the postintervention period. Fewer patients were exposed to antimicrobials with extended gram-negative (44.4% [71 of 160] vs 9.2% [15 of 163]; P<.001), anaerobic (39.4% [63 of 160] vs 9.8% [16 of 163]; P<.001), and antipseudomonal (16.3% [26 of 160] vs 1.8% [3 of 163]; P<.001) coverage. The mean length of stay decreased from 3.6 to 2.2 days (P<.001) without an increase in 30-day readmissions (6.3% [10 of 160] vs 4.9% [8 of 163]; P=.64). The ASP made recommendations for 125 patients, and 96% were accepted. CONCLUSION: Implementation of an ASP-bundled approach aimed at optimizing antibiotic therapy in the management of uSSTIs led to shorter durations of narrow-spectrum therapy as well as shorter hospital length of stay without adversely affecting hospital readmissions.

Vancomycin-associated Henoch-Schönlein purpura.

Intravenous vancomycin is a widely used antibiotics, but it causes different types of cutaneous hypersensitivity reactions, ranging from maculopapular rash, red-man syndrome, drug rash with eosinophilia and systemic symptoms, IgA bullous dermatosis, leukocytoclastic vasculitis, Stevens-Johnsons syndrome, to IgE-mediated anaphylaxis. We report an elderly patient with the end-stage renal disease presented with diffuse palpable purpura while receiving IV vancomycin therapy for methicillin-resistant Staphylococcus aureus septicemia. Histopathology of skin biopsy revealed perivascular infiltrates of leukocytoclastic debris with necrosis of the small-sized blood vessels. Direct immunofluorescence analysis demonstrated vivid IgA plus C3 immune-complex deposits localized to the vessel walls, and no immune complexes were noted on the dermoepidermal junction. There was no IgG or IgM immunoreactivity detected on the tissue specimen. Rheumatologic disease work-ups were negative. A diagnosis of vancomycin-associated Henoch-Schönlein variant of vasculitis was made. Vancomycin was substituted by daptomycin, and the purpuric skin rashes were resolved. Since vancomycin is a commonly used antibacterial agent, clinicians are encouraged to have a heightened awareness of this rare adverse skin reaction. Early recognition and prompt discontinuation of the medication is the key in management. As it is not an Ig-E mediated reaction, desensitization of vancomycin or re-challenge with vancomycin is not recommended as re-exposure to the drug may result in a recurrence of similar manifestations with potential permanent renal failure.

Appropriateness of antibiotic management of uncomplicated skin and soft tissue infections in hospitalized adult patients.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a leading cause for hospitalizations in the United States. Few studies have addressed the appropriateness of antibiotic therapy in the management of SSTIs without complicating factors. We aimed to determine the appropriateness of antibiotic treatment duration for hospitalized adult patients with uncomplicated SSTIs. METHODS: This was a retrospective analysis performed at two academic medical centers in Pittsburgh, Pennsylvania on patients aged 18 years and older with primary ICD-9 code for SSTIs admitted August 1st, 2014-March 31st, 2015. The primary outcome was the appropriateness of antibiotic treatment duration for uncomplicated SSTIs. Secondary objectives included the appropriateness of antibiotic agent spectrum, duration of inpatient length of stay (LOS), utilization of blood cultures and advanced imaging modalities, and re-hospitalization for SSTI within 30 days of discharge from the index admission. RESULTS: A total of 163 episodes were included in the cohort. The mean duration of total antibiotic therapy was 12.6 days. Appropriate duration was defined as receipt of total antibiotic duration of less than 10 days and occurred in 20.2% of patients. Twenty eight percent of patients received antibiotics for greater than 14 days. Seventy three (44.8%) patients received greater than 24 h of inappropriate extended spectrum gram-negative coverage; 65 (39.9%) received anaerobic coverage. CONCLUSIONS: In the majority of patients, treatment duration was excessive. Inappropriate broad spectrum antibiotic selection was utilized with regularity for SSTIs without complicating factors. The management of uncomplicated SSTIs represents a significant opportunity for antimicrobial stewardship.

The thyroid hormone-inactivating type III deiodinase is expressed in mouse and human beta-cells and its targeted inactivation impairs insulin secretion.

Deiodinases are selenoproteins that activate or inactivate thyroid hormone. During vertebrate development, these pathways control thyroid hormone action in a cell-specific fashion explaining how systemic thyroid hormone can affect local control of tissue embryogenesis. Here we investigated the role of the thyroid hormone-inactivating deiodinase (D3) in pancreatic islet function and glucose homeostasis. D3 expression was determined by real-time PCR, immunofluorescence, and enzyme activity. Embryonic and adult wild-type mice and Mice with targeted disruption of Dio3 gene (D3KO) as well as human fetal pancreas and adult islets were studied. Insulin secretion was evaluated in adult mouse isolated islets. We found Dio3 gene expression and protein highly expressed in embryonic and adult pancreatic islets, predominantly in ß-cells in both humans and mice. However, mRNA levels were barely detectable for both the thyroid hormone-activating deiodinases types 1 and 2. D3KO animals were found to be glucose intolerant due to in vitro and in vivo impaired glucose-stimulated insulin secretion, without changes in peripheral sensitivity to insulin. D3KO neonatal (postnatal day 0) and adult pancreas exhibited reduced total islet area due to reduced ß-cell mass, insulin content, and impaired expression of key ß-cells genes. D3 expression in perinatal pancreatic ß-cells prevents untimely exposure to thyroid hormone, the absence of which leads to impaired ß-cell function and subsequently insulin secretion and glucose homeostasis. An analogous role is likely in humans, given the similar D3 expression pattern.