Dalbavancin stands up to severe skin infections

DENVER – Once-weekly intravenous dalbavancin was effective against acute bacterial skin and skin structure infections, and not inferior to twice-daily IV vancomycin followed by oral linezolid, results from a randomized, double-blind study showed.

Dalbavancin is an investigational lipoglycopeptide being developed by Branford, Conn.–based Durata Therapeutics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive microorganisms.

ABSSSIs are common and are among the most frequent indications for antibiotic therapy and hospitalization of adults in the United States today, Dr. Helen W. Boucher said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented. ABSSSIs are most often caused by Staphylococcus aureus and streptococci.

"Increasing antimicrobial resistance presents a particular treatment challenge and limits options available for the treatment of these infections," said Dr. Boucher of Tufts Medical Center, Boston. "Treatment of ABSSSI can involve substantial costs in terms of direct medical costs and time away from work or school. The pharmacokinetics of dalbavancin allow once weekly dosing, which is more convenient for patients and increases adherence to therapy. It may allow patients to be treated without being admitted to the hospital or allow for shorter hospital stays," she said.

In the study, known as DISCOVER 1, a total of 573 patients with severe ABSSSI were randomized to receive either dalbavancin 1 g IV over 30 minutes on day 1 followed by 500 mg IV on day 8; or vancomycin 1 g or 15 mg/kg IV every 12 hours for at least 3 days, with an option to switch to oral linezolid 600 mg every 12 hours.

The primary endpoint for regulatory review in the United States was combined factors known as the early response endpoint – cessation of the spread of the erythema of the infection, and the absence of fever at 48-72 hours after treatment initiation.

Overall, 83.3% of patients in the dalbavancin group achieved the early response endpoint compared with 81.8% of patients in the vancomycin group, for a difference of 1.5%. The most commonly reported adverse events in the dalbavancin and vancomycin/linezolid groups were nausea (4.2% vs. 4.6%, respectively), diarrhea (1.4% vs. 3.9%), headache (4.9% vs. 4.9%), pruritus (0.4% vs. 3.9%), hypertension (2.5% vs. 2.5%), rash (2.1% vs. 2.1%), and asthenia (0.4% vs. 2.1%).

Dr. Boucher, director of the infectious diseases fellowship program and an associate professor of medicine at Tufts, characterized the findings as especially impressive, considering that patients in DISCOVER 1 had very large skin lesions (a median area of about 333 cm²), and high frequencies of fever (85%) and systemic inflammatory response syndrome (61%), which is a marker of very severe illness. "It means that the drug stood up to very ill patients," she said.

She acknowledged certain limitations of the study, including the fact that adherence to twice-daily therapy with vancomycin/linezolid "may not be as high in a real-world setting as that seen in a closely monitored clinical trial setting."

Dr. Boucher disclosed that she is a scientific adviser for Durata Therapeutics, which sponsored the study, and has ties to numerous other pharmaceutical companies.

[email protected]

DENVER – Once-weekly intravenous dalbavancin was effective against acute bacterial skin and skin structure infections, and not inferior to twice-daily IV vancomycin followed by oral linezolid, results from a randomized, double-blind study showed.

Dalbavancin is an investigational lipoglycopeptide being developed by Branford, Conn.–based Durata Therapeutics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive microorganisms.

ABSSSIs are common and are among the most frequent indications for antibiotic therapy and hospitalization of adults in the United States today, Dr. Helen W. Boucher said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented. ABSSSIs are most often caused by Staphylococcus aureus and streptococci.

"Increasing antimicrobial resistance presents a particular treatment challenge and limits options available for the treatment of these infections," said Dr. Boucher of Tufts Medical Center, Boston. "Treatment of ABSSSI can involve substantial costs in terms of direct medical costs and time away from work or school. The pharmacokinetics of dalbavancin allow once weekly dosing, which is more convenient for patients and increases adherence to therapy. It may allow patients to be treated without being admitted to the hospital or allow for shorter hospital stays," she said.

In the study, known as DISCOVER 1, a total of 573 patients with severe ABSSSI were randomized to receive either dalbavancin 1 g IV over 30 minutes on day 1 followed by 500 mg IV on day 8; or vancomycin 1 g or 15 mg/kg IV every 12 hours for at least 3 days, with an option to switch to oral linezolid 600 mg every 12 hours.

The primary endpoint for regulatory review in the United States was combined factors known as the early response endpoint – cessation of the spread of the erythema of the infection, and the absence of fever at 48-72 hours after treatment initiation.

Overall, 83.3% of patients in the dalbavancin group achieved the early response endpoint compared with 81.8% of patients in the vancomycin group, for a difference of 1.5%. The most commonly reported adverse events in the dalbavancin and vancomycin/linezolid groups were nausea (4.2% vs. 4.6%, respectively), diarrhea (1.4% vs. 3.9%), headache (4.9% vs. 4.9%), pruritus (0.4% vs. 3.9%), hypertension (2.5% vs. 2.5%), rash (2.1% vs. 2.1%), and asthenia (0.4% vs. 2.1%).

Dr. Boucher, director of the infectious diseases fellowship program and an associate professor of medicine at Tufts, characterized the findings as especially impressive, considering that patients in DISCOVER 1 had very large skin lesions (a median area of about 333 cm²), and high frequencies of fever (85%) and systemic inflammatory response syndrome (61%), which is a marker of very severe illness. "It means that the drug stood up to very ill patients," she said.

She acknowledged certain limitations of the study, including the fact that adherence to twice-daily therapy with vancomycin/linezolid "may not be as high in a real-world setting as that seen in a closely monitored clinical trial setting."

Dr. Boucher disclosed that she is a scientific adviser for Durata Therapeutics, which sponsored the study, and has ties to numerous other pharmaceutical companies.

[email protected]

DENVER – Once-weekly intravenous dalbavancin was effective against acute bacterial skin and skin structure infections, and not inferior to twice-daily IV vancomycin followed by oral linezolid, results from a randomized, double-blind study showed.

Dalbavancin is an investigational lipoglycopeptide being developed by Branford, Conn.–based Durata Therapeutics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive microorganisms.

ABSSSIs are common and are among the most frequent indications for antibiotic therapy and hospitalization of adults in the United States today, Dr. Helen W. Boucher said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented. ABSSSIs are most often caused by Staphylococcus aureus and streptococci.

"Increasing antimicrobial resistance presents a particular treatment challenge and limits options available for the treatment of these infections," said Dr. Boucher of Tufts Medical Center, Boston. "Treatment of ABSSSI can involve substantial costs in terms of direct medical costs and time away from work or school. The pharmacokinetics of dalbavancin allow once weekly dosing, which is more convenient for patients and increases adherence to therapy. It may allow patients to be treated without being admitted to the hospital or allow for shorter hospital stays," she said.

In the study, known as DISCOVER 1, a total of 573 patients with severe ABSSSI were randomized to receive either dalbavancin 1 g IV over 30 minutes on day 1 followed by 500 mg IV on day 8; or vancomycin 1 g or 15 mg/kg IV every 12 hours for at least 3 days, with an option to switch to oral linezolid 600 mg every 12 hours.

The primary endpoint for regulatory review in the United States was combined factors known as the early response endpoint – cessation of the spread of the erythema of the infection, and the absence of fever at 48-72 hours after treatment initiation.

Overall, 83.3% of patients in the dalbavancin group achieved the early response endpoint compared with 81.8% of patients in the vancomycin group, for a difference of 1.5%. The most commonly reported adverse events in the dalbavancin and vancomycin/linezolid groups were nausea (4.2% vs. 4.6%, respectively), diarrhea (1.4% vs. 3.9%), headache (4.9% vs. 4.9%), pruritus (0.4% vs. 3.9%), hypertension (2.5% vs. 2.5%), rash (2.1% vs. 2.1%), and asthenia (0.4% vs. 2.1%).

Dr. Boucher, director of the infectious diseases fellowship program and an associate professor of medicine at Tufts, characterized the findings as especially impressive, considering that patients in DISCOVER 1 had very large skin lesions (a median area of about 333 cm²), and high frequencies of fever (85%) and systemic inflammatory response syndrome (61%), which is a marker of very severe illness. "It means that the drug stood up to very ill patients," she said.

She acknowledged certain limitations of the study, including the fact that adherence to twice-daily therapy with vancomycin/linezolid "may not be as high in a real-world setting as that seen in a closely monitored clinical trial setting."

Dr. Boucher disclosed that she is a scientific adviser for Durata Therapeutics, which sponsored the study, and has ties to numerous other pharmaceutical companies.

[email protected]