Journal Feed Weekly Wrap-Up

We always work hard, but we may not have time to read through a bunch of journals. It’s time to learn smarter. 
Originally published at JournalFeed, a site that provides daily or weekly literature updates. 
Follow Dr. Clay Smith at @spoonfedEM, and sign up for email updates here.

#1: Dalbavancin – ADVANCE-ing Treatment of Soft Tissue Infections?

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The ADVANCE trial showed significant reduction in hospitalization rates solely for IV antibiotics in patients with uncomplicated mild to moderate skin infections.

Why does this matter?
IV antibiotic administration is the only reason for hospital admission for approximately 40% of patients with uncomplicated skin and soft tissue infections (SSTIs). In a system that is already stressed, dalbavancin administration and discharge could decrease health care utilization and improve patient satisfaction. But does it work?

Dalbavancin is a novel second-generation lipoglycopeptide antibiotic belonging to the same class as vancomycin. This medication reaches steady state after 3 days and has a half-life of 8.5 days making it ideal for outpatient management of soft tissue infections.

The ADVANCE trial was a superiority study in which 11 US academically affiliated EDs served as their own control with implementation of usual care (“pre-intervention” – vancomycin, cefazolin, or ceftriaxone and admission) and clinical pathway (“post-intervention” – dalbavancin and discharge). The primary outcome was rate of initial hospitalization, and dalbavancin was associated with significant reduction (50%). With regard to secondary outcomes, this study demonstrated decreased healthcare utilization, similar adverse events, and improvement of patient satisfaction with the intervention group as well.

This study suggests that a “treat and street” option is an option for uncomplicated SSTIs that otherwise would have been admitted for IV antibiotics alone.

The most important side note of this study is the fact that dalbavancin was provided free of charge; further cost-analyses are needed to make sure that this pathway decreases overall healthcare costs.

Editor’s note: Thankfully, we have a cost analysis of dalbavancin on deck for tomorrow! Spoiler alert – it’s not cheap. ~Clay Smith

Pathway with single-dose long-acting intravenous antibiotic reduces emergency department hospitalizations of patients with skin infections. Acad Emerg Med. 2021 Oct;28(10):1108-1117. doi: 10.1111/acem.14258. Epub 2021 May 5.

#2: Dalbavancin – Greater Cost, Lower Success?

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Single-dose dalbavancin treatment for skin and soft tissue infections came at a higher cost and higher risk of failure than conventional therapy.

Why does this matter?
Patients are typically eager to avoid hospitalization. A single-dose IV antibiotic for skin and soft tissue infection offers flexibility to treatment plans and the potential for monitoring at home. But these long-acting drugs come at a high cost, with potential risk for recurrent infection. How did dalbavancin perform in this study?

Is treat and street better?
This was a multi-center retrospective study that evaluated the net cost of care per patient over a 27 month period for adults diagnosed with acute bacterial skin and skin structure infections (ABSSI) treated either with dalbavancin or standard of care treatment.

Treatment with dalbavancin had a higher net cost for the hospital (revenue minus total cost) of $1685 per patient compared with $75 in patients who received standard of care. Additionally, treatment success rate (defined as no 30-day hospital readmission) was lower in those who received dalbavancin (74%) vs standard of care (85%), p=0.004.

While dalbavancin may be used as a single-dose IV antibiotic to treat patients with moderate to severe skin and soft tissue infections to reduce initial hospitalization rates, it had a higher overall net cost and a lower treatment success rate in this cohort when compared with standard of care treatment. Additionally, patients with high risk conditions, such as being immunocompromised, using IV drugs, and having antibiotic-resistant infections may have an even higher risk of failing treatment with dalbavancin and requiring hospital readmission. However, there are specific populations in which dalbavancin can be considered, such as patients who may have difficulty with medication adherence or medical literacy regarding dosing and duration of treatment.

Cost-Consequence Analysis of Single-Dose Dalbavancin Versus Standard of Care for the Treatment of Acute Bacterial Skin and Skin Structure Infections in a Multisite Healthcare System. Clin Infect Dis. 2021 Oct 5;73(7):e1436-e1442. doi: 10.1093/cid/ciaa1732.

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Use of REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, for patients with Covid-19 infection was associated with faster symptom resolution and reduced risk of hospitalization or death compared to placebo.

Why does this matter?
The Covid-19 pandemic has sickened more than 240 million people and has resulted in almost 5 million deaths. Although most individuals infected with SARS-CoV-2 only have mild to moderate disease, some patients develop severe infection that can lead to hospitalization and death. We know that dexamethasone is helpful for patients with severe COVID-19 disease who require respiratory support, but are there any evidence-based treatment options for the vast majority of patients with only mild to moderate disease?

Monoclonal antibodies for the win!

Design: This was the phase 3 portion of an adaptive trial of outpatient individuals with Covid-19 infection and risk factors for severe disease who were randomized to receive various doses of REGEN-COV or placebo (normal saline). Patients were enrolled between September 24, 2020 and January 17, 2021 and were followed through day 29.

Results: Covid-19 related hospitalization or death occurred in 1.3% of patients in the REGEN-COV 2400-mg group compared to 4.6% of patients in the concurrent placebo group (relative risk reduction, 71.3%; P<0.001) and in 1.0% of patients in the REGEN-COV 1200-mg group compared to 3.2% of patients in the concurrent placebo group (relative risk reduction, 70.4%; P=0.002). Median time to symptom resolution was 4 days shorter for each REGEN-COV dose group compared to placebo (10 days vs 14 days; P<0.001). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. All REGEN-COV dose levels were associated with more rapid declines in viral load.

Adverse events were rare and more common in the placebo group (4.0%) than the REGEN-COV groups (1.1% 1200-mg group, 1.3% 2400-mg group). Less than 0.3% of patients had grade 2 or higher infusion-related reactions.

Implications: This data supports the use of REGEN-COV treatment for patients with Covid-19 who are at high risk of severe disease. REGEN-COV leads to reduced risk of Covid-19 hospitalization or death, allows for faster symptom resolution, and has been listed in the NIH treatment guidelines for high-risk outpatients with Covid-19.

Limitations: The study was funded by Regeneron Pharmaceuticals and was not powered to find a difference in mortality. Overall, only 5 deaths occurred (2 in the REGEN-COV groups and 3 in the placebo groups). In addition, this data was collected before the Delta variant was the dominant strain (although in vitro studies have shown REGEN-COV has efficacy against circulating variants of concern including the alpha, beta, delta, and gamma variants).

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021 Sep 29;NEJMoa2108163. doi: 10.1056/NEJMoa2108163. Online ahead of print.

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