Telavancin Adds Option for Obese Patients with SSSIs

CHICAGO – In obese patients, the antibiotic telavancin may offer an alternative to vancomycin for treating complicated skin and skin structure infections, according to a post hoc analysis.

In the analysis of two phase III trials, Christine M. Slover, Pharm.D., and colleagues, found that obese patients had nearly identical rates of clinical cure of their skin and skin structure infections (SSSI) whether treated with telavancin or vancomycin (72% vs. 73%). However, those in the telavancin group were more likely to have serious adverse events (11% vs. 3%).

The cure rates and adverse event rates with telavancin were generally similar to those seen in nonobese patients from the same trials, said Dr. Slover, a senior project manager at Astellas Pharma Global Development, in Deerfield, Ill.

"If you have a patient who has a complicated skin infection for whom other agents that are available might not be an option, telavancin is something you can consider, even in obese patients," Dr. Slover commented in an interview at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Telavancin is a once-a-day drug, and there is no therapeutic drug monitoring required," she added. In contrast, vancomycin is given at least twice a day and drug levels must be checked. "Cost wise, vancomycin has been available for 50 years and is generic and costs pennies a day; telavancin is a branded drug, so it does cost more because of that."

In addition, severely obese patients were 31% less likely than other obese patients and nonobese patients to achieve clinical cure of their SSSI, no matter which antibiotic they received. Such patients "have a lot of peripheral vascular disease, so it’s much harder to get the antibiotic to the sites of infection," Dr. Slover commented at the conference, which was sponsored by the American Society for Microbiology.

"If you have a patient who has a complicated skin infection for whom other agents might not be an option, telavancin is something you can consider."

The researchers analyzed data from the Assessment of Telavancin in Complicated Skin and Skin Structure Infections (ATLAS) trials, which were identical randomized, double-blind trials conducted among 1,867 adults with complicated SSSIs due to suspected or confirmed gram-positive pathogens (Clin. Infect. Dis. 2008;46:1683-93).

Patients were randomized 1:1 to treatment with telavancin (10 mg/kg IV every 24 hours) or vancomycin (1 g IV every 12 hours) for 7 to 14 days.

"For SSSIs, over the last several years, there has been an increase in methicillin-resistant Staphylococcus aureus and a need for drugs that either are better than what’s already out there or more convenient than what’s already out there," Dr. Slover commented, giving some background. Telavancin (brand name Vibativ, manufactured by Astellas) was approved by the U.S. Food and Drug Administration about 2 years ago for the treatment of gram-positive complicated SSSIs in adults.

In the new analysis, she and her colleagues focused on the one-fifth of trial patients who were obese, having a body mass index of 35 kg/m² or greater. Most of this subset (86%) were younger than 65 years. Their leading diagnoses were cellulitis (51%) and abscess (33%). Substantial proportions had diabetes (42%), hypertension, (56%), and peripheral vascular disease (11%).

"Essentially, there was no difference in clinical cure rate between the two [treatment] groups," she reported: the rate was 72% with telavancin and 73% with vancomycin. (The corresponding rates in nonobese patients were 78% and 75%).

The rate of adverse events was 88% with telavancin and 76% with vancomycin (77% and 71% in nonobese patients), and the rate of serious adverse events was 11% with telavancin and 3% with vancomycin (7% and 5% in nonobese patients). Renal events were the leading type of serious adverse events with telavancin among obese patients.

In a multivariate analysis involving all patients in the trials, patients were less likely to have a clinical cure of their SSSI if they had bacteremia at baseline (odds ratio, 0.37), had congestive heart failure (0.43), were aged 65 years or older (0.74), or had a body mass index of at least 40 (0.69). Treatment group (telavancin vs. vancomycin) did not significantly predict this outcome.

In a second multivariate analysis, patients were more likely to have renal adverse events if they had hypertension at baseline (OR, 4.73), had poor renal function at baseline (4.66), were in the telavancin group (3.60), had at least two comorbidities versus none (3.14), or had cellulitis, an ulcer, or a burn (2.44). Patients were less likely to have such events if they were white (0.36) or had a body mass index between 25 and 30, compared with one of less than 18.5 (0.09).

Dr. Slover is an employee of Astellas Pharma Global Development. The trials were supported jointly by Astellas Pharma Global Development and Theravance.

CHICAGO – In obese patients, the antibiotic telavancin may offer an alternative to vancomycin for treating complicated skin and skin structure infections, according to a post hoc analysis.

In the analysis of two phase III trials, Christine M. Slover, Pharm.D., and colleagues, found that obese patients had nearly identical rates of clinical cure of their skin and skin structure infections (SSSI) whether treated with telavancin or vancomycin (72% vs. 73%). However, those in the telavancin group were more likely to have serious adverse events (11% vs. 3%).

The cure rates and adverse event rates with telavancin were generally similar to those seen in nonobese patients from the same trials, said Dr. Slover, a senior project manager at Astellas Pharma Global Development, in Deerfield, Ill.

"If you have a patient who has a complicated skin infection for whom other agents that are available might not be an option, telavancin is something you can consider, even in obese patients," Dr. Slover commented in an interview at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Telavancin is a once-a-day drug, and there is no therapeutic drug monitoring required," she added. In contrast, vancomycin is given at least twice a day and drug levels must be checked. "Cost wise, vancomycin has been available for 50 years and is generic and costs pennies a day; telavancin is a branded drug, so it does cost more because of that."

In addition, severely obese patients were 31% less likely than other obese patients and nonobese patients to achieve clinical cure of their SSSI, no matter which antibiotic they received. Such patients "have a lot of peripheral vascular disease, so it’s much harder to get the antibiotic to the sites of infection," Dr. Slover commented at the conference, which was sponsored by the American Society for Microbiology.

"If you have a patient who has a complicated skin infection for whom other agents might not be an option, telavancin is something you can consider."

The researchers analyzed data from the Assessment of Telavancin in Complicated Skin and Skin Structure Infections (ATLAS) trials, which were identical randomized, double-blind trials conducted among 1,867 adults with complicated SSSIs due to suspected or confirmed gram-positive pathogens (Clin. Infect. Dis. 2008;46:1683-93).

Patients were randomized 1:1 to treatment with telavancin (10 mg/kg IV every 24 hours) or vancomycin (1 g IV every 12 hours) for 7 to 14 days.

"For SSSIs, over the last several years, there has been an increase in methicillin-resistant Staphylococcus aureus and a need for drugs that either are better than what’s already out there or more convenient than what’s already out there," Dr. Slover commented, giving some background. Telavancin (brand name Vibativ, manufactured by Astellas) was approved by the U.S. Food and Drug Administration about 2 years ago for the treatment of gram-positive complicated SSSIs in adults.

In the new analysis, she and her colleagues focused on the one-fifth of trial patients who were obese, having a body mass index of 35 kg/m² or greater. Most of this subset (86%) were younger than 65 years. Their leading diagnoses were cellulitis (51%) and abscess (33%). Substantial proportions had diabetes (42%), hypertension, (56%), and peripheral vascular disease (11%).

"Essentially, there was no difference in clinical cure rate between the two [treatment] groups," she reported: the rate was 72% with telavancin and 73% with vancomycin. (The corresponding rates in nonobese patients were 78% and 75%).

The rate of adverse events was 88% with telavancin and 76% with vancomycin (77% and 71% in nonobese patients), and the rate of serious adverse events was 11% with telavancin and 3% with vancomycin (7% and 5% in nonobese patients). Renal events were the leading type of serious adverse events with telavancin among obese patients.

In a multivariate analysis involving all patients in the trials, patients were less likely to have a clinical cure of their SSSI if they had bacteremia at baseline (odds ratio, 0.37), had congestive heart failure (0.43), were aged 65 years or older (0.74), or had a body mass index of at least 40 (0.69). Treatment group (telavancin vs. vancomycin) did not significantly predict this outcome.

In a second multivariate analysis, patients were more likely to have renal adverse events if they had hypertension at baseline (OR, 4.73), had poor renal function at baseline (4.66), were in the telavancin group (3.60), had at least two comorbidities versus none (3.14), or had cellulitis, an ulcer, or a burn (2.44). Patients were less likely to have such events if they were white (0.36) or had a body mass index between 25 and 30, compared with one of less than 18.5 (0.09).

Dr. Slover is an employee of Astellas Pharma Global Development. The trials were supported jointly by Astellas Pharma Global Development and Theravance.

CHICAGO – In obese patients, the antibiotic telavancin may offer an alternative to vancomycin for treating complicated skin and skin structure infections, according to a post hoc analysis.

In the analysis of two phase III trials, Christine M. Slover, Pharm.D., and colleagues, found that obese patients had nearly identical rates of clinical cure of their skin and skin structure infections (SSSI) whether treated with telavancin or vancomycin (72% vs. 73%). However, those in the telavancin group were more likely to have serious adverse events (11% vs. 3%).

The cure rates and adverse event rates with telavancin were generally similar to those seen in nonobese patients from the same trials, said Dr. Slover, a senior project manager at Astellas Pharma Global Development, in Deerfield, Ill.

"If you have a patient who has a complicated skin infection for whom other agents that are available might not be an option, telavancin is something you can consider, even in obese patients," Dr. Slover commented in an interview at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Telavancin is a once-a-day drug, and there is no therapeutic drug monitoring required," she added. In contrast, vancomycin is given at least twice a day and drug levels must be checked. "Cost wise, vancomycin has been available for 50 years and is generic and costs pennies a day; telavancin is a branded drug, so it does cost more because of that."

In addition, severely obese patients were 31% less likely than other obese patients and nonobese patients to achieve clinical cure of their SSSI, no matter which antibiotic they received. Such patients "have a lot of peripheral vascular disease, so it’s much harder to get the antibiotic to the sites of infection," Dr. Slover commented at the conference, which was sponsored by the American Society for Microbiology.

"If you have a patient who has a complicated skin infection for whom other agents might not be an option, telavancin is something you can consider."

The researchers analyzed data from the Assessment of Telavancin in Complicated Skin and Skin Structure Infections (ATLAS) trials, which were identical randomized, double-blind trials conducted among 1,867 adults with complicated SSSIs due to suspected or confirmed gram-positive pathogens (Clin. Infect. Dis. 2008;46:1683-93).

Patients were randomized 1:1 to treatment with telavancin (10 mg/kg IV every 24 hours) or vancomycin (1 g IV every 12 hours) for 7 to 14 days.

"For SSSIs, over the last several years, there has been an increase in methicillin-resistant Staphylococcus aureus and a need for drugs that either are better than what’s already out there or more convenient than what’s already out there," Dr. Slover commented, giving some background. Telavancin (brand name Vibativ, manufactured by Astellas) was approved by the U.S. Food and Drug Administration about 2 years ago for the treatment of gram-positive complicated SSSIs in adults.

In the new analysis, she and her colleagues focused on the one-fifth of trial patients who were obese, having a body mass index of 35 kg/m² or greater. Most of this subset (86%) were younger than 65 years. Their leading diagnoses were cellulitis (51%) and abscess (33%). Substantial proportions had diabetes (42%), hypertension, (56%), and peripheral vascular disease (11%).

"Essentially, there was no difference in clinical cure rate between the two [treatment] groups," she reported: the rate was 72% with telavancin and 73% with vancomycin. (The corresponding rates in nonobese patients were 78% and 75%).

The rate of adverse events was 88% with telavancin and 76% with vancomycin (77% and 71% in nonobese patients), and the rate of serious adverse events was 11% with telavancin and 3% with vancomycin (7% and 5% in nonobese patients). Renal events were the leading type of serious adverse events with telavancin among obese patients.

In a multivariate analysis involving all patients in the trials, patients were less likely to have a clinical cure of their SSSI if they had bacteremia at baseline (odds ratio, 0.37), had congestive heart failure (0.43), were aged 65 years or older (0.74), or had a body mass index of at least 40 (0.69). Treatment group (telavancin vs. vancomycin) did not significantly predict this outcome.

In a second multivariate analysis, patients were more likely to have renal adverse events if they had hypertension at baseline (OR, 4.73), had poor renal function at baseline (4.66), were in the telavancin group (3.60), had at least two comorbidities versus none (3.14), or had cellulitis, an ulcer, or a burn (2.44). Patients were less likely to have such events if they were white (0.36) or had a body mass index between 25 and 30, compared with one of less than 18.5 (0.09).

Dr. Slover is an employee of Astellas Pharma Global Development. The trials were supported jointly by Astellas Pharma Global Development and Theravance.