tedizolid-phosphate and oritavancin

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibit in vitro activity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstrate in vitro activity against VRE. These new Gram-positive agents are reviewed here.

Topics: Anti-Infective Agents; Drug Approval; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Organophosphates; Oxazoles; Teicoplanin; United States; Vancomycin-Resistant Enterococci

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: Acute Disease; Anti-Bacterial Agents; Glycopeptides; Humans; Lipoglycopeptides; Organophosphates; Oxazoles; Skin Diseases, Bacterial; Teicoplanin

The FDA guidance published in 2013 provided requirements for conducting ABSSSI trials. In 2014, dalbavancin, oritavancin, and tedizolid were introduced into the market after phase III noninferiority clinical trials against vancomycin (for the lipoglycopeptides) and linezolid (for tedizolid), demonstrating clinical efficacy for the treatment of ABSSSI. Great interest exists for these agents because of the postulated financial impact. Due to favorable pharmacokinetics which allow for less frequent medication administration and shorter treatment durations, these agents may prove to reduce hospital admissions and length of stay.

Topics: Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Costs and Cost Analysis; Glycopeptides; Humans; Lipoglycopeptides; Organophosphates; Oxazoles; Practice Guidelines as Topic; Skin Diseases, Bacterial; Teicoplanin; Treatment Outcome

Topics: Antibodies, Monoclonal, Humanized; Benzhydryl Compounds; Benzofurans; Cyclopropanes; Diphosphates; Drug Approval; Drug Therapy; Glucagon-Like Peptide 1; Glucosides; Glycopeptides; Humans; Lactones; Lipoglycopeptides; Organophosphates; Oxazoles; Pyridines; Sulfates; Teicoplanin; United States; United States Food and Drug Administration

Topics: Anti-Bacterial Agents; Drug Approval; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Organophosphates; Oxazoles; Streptococcal Infections; Teicoplanin; United States; United States Food and Drug Administration