oritavancin and Staphylococcal-Skin-Infections

In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

Topics: Ambulatory Care; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Lipoglycopeptides; Organophosphates; Oxazoles; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Teicoplanin; United States; United States Food and Drug Administration

Topics: Administration, Intravenous; Anti-Bacterial Agents; Carrier State; Double-Blind Method; Drug Resistance, Bacterial; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Nasal Mucosa; Staphylococcal Skin Infections; Staphylococcus aureus

Oritavancin is a new lipoglycopeptide antibacterial agent with an exceptionally long terminal half-life and a rapid bactericidal effect. Multiple mechanisms of action lead to a broad activity against Gram-positive bacteria, such as staphylococci, streptococci and enterococci, including methicillin-resistant Staphylococcus aureus. Its long terminal half-life allows for single-dose treatment of acute bacterial skin and skin structure infections. Oritavancin was found to be safe and effective in treating acute bacterial skin and skin structure infections in adults and it is currently approved in the USA and in Europe for this indication. Unfortunately, data for other indications are lacking. Here, we review chemistry, microbiology, pharmacology, efficacy and tolerability of oritavancin.

Topics: Adult; Anti-Bacterial Agents; Enterococcus; Europe; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Half-Life; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Skin Infections; Streptococcus

It is estimated that acute bacterial skin and skin structure infections (ABSSSI) account for nearly 10% of hospital admissions and 3.4-3.8 million emergency department visits per year in the United States. Analyses of hospital discharge records indicate 74% of ABSSSI admissions involve empiric treatment with methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics. Analysis has shown that payer costs could be reduced if moderate-to-severe ABSSSI patients were treated to a greater extent in the observational unit followed by discharge to outpatient parenteral antibiotic therapy (OPAT). Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against gram-positive bacteria, including MRSA.. To estimate the impact on a U.S. payer's budget of using single-dose oritavancin in ABSSSI patients with suspected MRSA involvement who are indicated for intravenous antibiotics.. A decision analytic model based on current clinical practice was developed to estimate the economic value of decreased hospital resource consumption by using single-dose oritavancin over a 1-year time horizon. Use of antibiotics was informed by an analysis of the Premier Research Database. Demographic and clinical data were derived from a targeted literature review. Emergency department, observation, laboratory, and administration costs used were Medicare National Limitation amounts. Drug costs were 2014 wholesale acquisition costs.. For a hypothetical U.S. payer with 1,000,000 members, it is expected that approximately 14,285 members per year will be diagnosed with ABSSSI severe enough to indicate intravenous antibiotics with MRSA activity. Based on this simulation, use of single-dose oritavancin in 26% of these patients was estimated to reduce the number of inpatient admissions, reduce length of stay for patients requiring admission, and reduce the number of days a patient needs to receive daily infusions in the OPAT clinic. The total patient days decreased from 171,125 to 133,435 with a total annual budget impact of -$12,550,000 or -$1.05 per member per month (PMPM). Total inpatient and outpatient costs were reduced by $9,970,000 (19.7%) and $2,580,000 (4.2%), respectively. Inpatient cost savings were derived from a reduction in admissions, length of stay, and lower drug administration burden. Outpatient costs were reduced by lower drug administration burden in the OPAT setting. A sensitivity analysis demonstrated that the model was most sensitive to population estimates.. Use of single-dose oritavancin in moderate-to-severe ABSSSI patients, including those with suspected MRSA, was projected to deliver an estimated cost reduction to U.S. payers of $1.05 PMPM by avoiding hospitalization in appropriate patients and reducing outpatient costs associated with multiday parenteral antibiotic therapy.. This work was funded by The Medicines Company. Jensen, Wu, and Cyr are employees of ICON Health Economics, which provides consulting services to the biopharmaceutical industry, including The Medicines Company. Fan and Sulman are employees and shareholders of The Medicines Company. Dufour and Lodise have provided consulting services to The Medicines Company. Nicolau provided model input but did not receive an honorarium for contributions on this project. Nicolau is a speaker for The Medicines Company. Study concept and design were contributed by Jensen and Wu, along with the other authors. Jensen, Wu, Fan, and Sulham collected the data, with assistance from Cyr. Data interpretation was performed by Sulham, Jensen, Wu, and Fan, assisted by Lodise, Nicolau, and Dufour. The manuscript was written by Jensen, Wu, and Sulham, with assistance from Cyr, and revised by Lodise, Nicolau, and Dufour, with assistance from the other authors.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Budgets; Decision Trees; Glycopeptides; Humans; Insurance, Health, Reimbursement; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Severity of Illness Index; Staphylococcal Skin Infections; United States

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Skin Infections; Staphylococcus aureus; Vancomycin