快樂小藥師 Im pharmacist nichts glücklich

A new antibiotic, tedizolid phosphate, appears to be a reasonable alternative to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI): A short (6-day) course of tedizolid phosphate was as effective as a 10-day course of linezolid with regard to both early and sustained clinical responses.

Philippe Prokocimer, MD, from Trius Therapeutics in San Diego, California, and colleagues published the results of their efficacy and safety trial in the February 13 issue of JAMA. The study was conducted from August 2010 through September 2011 at 81 centers throughout North America, Latin America, and Europe. The intent-to-treat analysis included data from 667 adults with ABSSSI treated with either tedizolid phosphate (n = 332) or linezolid (n = 335).

When early clinical response was measured 48 to 72 hours after initiating therapy for an ABSSSI, tedizolid phosphate (79.5% response rate; 95% confidence interval, 74.8% - 83.7%) was found to be statistically noninferior to linezolid (79.4% response rate; 95% confidence interval, 74.7% - 83.6%).

William Schaffner, MD, infectious diseases specialist at Vanderbilt University School of Medicine, Nashville, Tennessee, reviewed the study and discussed it by telephone with Medscape Medical News. Dr. Schaffner expressed enthusiasm about the new antibiotic, explaining that the Infectious Diseases Society of America has been working with the US Food and Drug Administration (FDA) to promote new research that would aid the development of new antibiotics.

Although many disease states create markets for long-term or even lifelong drugs, infectious disease experts increasingly seek a shorter duration of therapy. Moreover, these experts closely guard new antibiotics and are reluctant to prescribe them until emerging antibiotic resistance makes the current arsenal of antibiotics ineffective. In Dr. Schaffner's words, "The economic incentives for developing new antibiotics have been a disaster."

The new FDA environment allows new drugs to be tested against established first-line drugs, which makes it possible for researchers to gather much better comparative efficacy and safety data for new drugs.

Dr. Schaffner described tedizolid phosphate as the first drug to make it through a new, well-lubricated maze created by the October 1, 2012, Generating Antibiotic Incentives Now (GAIN) Act. The GAIN Act mandates priority reviews for antibiotic new drug applications and adds an additional 5 years of market exclusivity for new antibiotics. The GAIN Act also adds a pathogen-focused pathway that allows a new drug application to be supported by multiple clinical trials of the same infection, but in different parts of the body.

The current study therefore represents a larger societal interest than a typical phase 3 clinical trial, in that it suggests that the GAIN Act will lead to the development of new antibiotics that are desperately needed as antibiotic resistance becomes increasingly widespread. Dr. Schaffner added, "That's why this study was published in JAMA as opposed to an obscure infectious disease journal.... [It] bodes well for the development of new antibiotics."

Although infectious disease experts have many reasons to be hopeful about antibiotic drug development, the practicing clinician should know that, "We have a new antibiotic that is effective against these seemingly superficial, but possibly serious, skin infections," he added. Dr. Schaffner also noted that the once-daily dosing and shorter dosing of tedizolid phosphate are likely to improve patient compliance.

The trial was funded and conducted by Trius Therapeutics. Dr. Prokocimer and 2 coauthors each reported holding stock/stock options in Trius Therapeutics, and each was an employee at the time the work and analyses were performed. One coauthor has reported receiving the following from Trius Therapeutics: consulting fees, support for travel expenses, fees for participating in review activities, and payment for writing or reviewing the manuscript; as well as serving as a consultant to Cerexa Inc, Achaogen Inc, Nabriva Therapeutics, Durata Therapeutics, Cubist Pharmaceuticals Inc, Cempra Pharmaceuticals Inc, Polymedix Inc, and Kalidex Inc. Another coauthor and Dr. Schaffner disclosed no relevant financial relationships.