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Telavancin and Vancomycin for Treatment of Complicated Skin and Skin Structure Infections: Presented at ECCMID-ICC

By Chris Berrie

MUNICH, GERMANY -- April 5, 2007 -- The novel bactericidal lipoglycopeptide telavancin has an acceptable adverse events profile and is non-inferior to standard use of vancomycin treatment of patients with complicated skin and skin-structure infections (cSSSIs), according to a combined analysis of the 2 methodologically identical, international, active-controlled, double-blind, randomised phase 3 ATLAS trials.

David Friedland, MD, senior director (clinical), clinical research, Theravance Inc., South San Franciso, California, United States, presented the results of this analysis here on April 1^st at the joint 17^th European Congress of Clinical Microbiology and Infectious Diseases and 25^th International Congress on Chemotherapy (ECCMID-ICC).

Dr. Friedland is a member of the Assessment of Telavancin in Skin and Skin Structure Infections (ATLAS) group.

Telavancin displays a multifunctional mechanism of action against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). S. aureus is a common cause of cSSSIs and MRSA is a common pathogen in isolates from cSSSIs.

The prevalence of infection involving MRSA strains is increasing, Dr. Friendland said, so the ATLAS studies were designed to compare the safety and efficacy of telavancin with that of vancomycin in the treatment of patients with cSSSIs.

"[The evaluation] wasn't specifically for MRSA, but we really asked the sites to enrol patients who were at high risk for MRSA, and so these studies had the largest amounts of MRSA patients that any study has ever enrolled," explained Dr. Friedland.

The study enrolled patients who were 18 years of age or more. They had cSSSIs with MRSA either suspected or confirmed as the primary pathogen. Standard exclusion criteria were also applied.

The full combined analysis populations from ATLAS 1 and 2 included a total of 928 patients on telavancin and 939 on vancomycin (all-treated patients), of which 1,383 (telavancin, 680; vancomycin, 703) were classified as the modified all-treated population. Further, of these, there were 1,489 (telavancin, 745; vancomycin, 744) who were clinically evaluable, 1,063 (telavancin, 527; vancomycin, 536) who were microbiologically evaluable, and 579 (telavancin, 278; vancomycin, 301) who were microbiologically evaluable and had MRSA.

Following the randomisation of the 1,867 patients who satisfyed the necessary criteria, 928 (mean age, 48.8 years; male, 56%) received telavancin 10 mg/kg IV every 24 h, and 939 (mean age, 48.7 years; male, 60%) received vancomycin 1 g IV every 12 hour for 7 to 14 days. Dose adjustments were permitted according to site-specific standard operating procedures.

Concomitant antibacterial therapy with aztreonam and/or metroidazole was permitted for patients with suspected or confirmed polymicrobial infections.

At baseline, the 2 treatment arms were similar for the wide range of demographics and disease characteristics monitored, including body weight, concomitant conditions (obesity, diabetes mellitus, renal insufficiency), type of cSSSI (major abscess, deep/ extensive cellulitis, wound infection, infected ulcer, infected burn) and site of primary infection (upper/lower extremities, front/back torso, head/neck).

The clinically evaluable patient population was comprised of those with a clinical response at test-of-cure (TOC) 7 to 14 days after last dose of study drug).

The combined clinical cure for ATLAS 1 and 2 showed no significant differences between telavancin and vancomycin (88.3% vs 87.1%, respectively).

For the microbiological evaluation, again there were no significant differences between these 2 treatment groups: 89.8% versus 87.3%, respectively. The combination of clinical cure plus microbiological eradication, providing the overall therapeutic response, was therefore the same between these 2 treatments: 88.6% versus 86.2%, respectively.

While the specific analysis of these results for the MRSA subset of microbiologically evaluable patients also showed no significant differences between these 2 treatment arms, Dr. Friedland noted that there was a trend in favour of telavancin over vancomycin, respectively: clinical sure, 90.6% vs 86.4%; microbiological eradication, 89.9% vs 85.4%; overall therapeutic response, 89.9% vs 84.7%.

For the all-treated population, the rates of overall total adverse events were similar in the 2 groups (79% vs 72%), although the serious adverse events (7% vs 4%) and discontinuations due to adverse events (8% vs 6%) were slightly greater for telavancin.

The general breakdown of adverse events according to category, and as reported by 3% or more of the patients in each treatment group, showed generally similar rates between telavancin and vancomycin, although there were higher rates in particular with telavancin for taste disturbance (33% vs 7%, respectively), nausea (27% vs 15%), vomiting (14% vs 7%) and foamy urine (13% vs 3%). The reverse was the case for pruritis (6% vs 13%) and generalised pruritis (3% vs 6%).

"[Telavancin] met all its study endpoints, which is non-inferiority to vancomycin, and the safety profile is consistent with what you would expect for an intravenous antibiotic," Dr. Friedland said

He also indicated that there was a trend noted for improved responses for telavancin, and more specifically in the patients with a cSSSI associated with MRSA.

Thus, these data support the efficacy and safety of this once daily treatment with telavancin for Gram-positive cSSSIs, he concluded.

This study was supported by Astellas and Theravance Inc.


[Presentation title: The ATLAS Studies: Double-Blind, Randomised, Active-Controlled, Multinational, Phase 3 Trials Comparing Telavancin With Vancomycin for the Treatment of Complicated Skin and Skin Structure Infections. Abstract P844]

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