Antimicrobial Agents and Chemotherapy: Recombinant Protein for Severe Sepsis
Speaker: Steven P. LaRosa, MD, Associate Staff Physician, Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio.
Drotreogin alfa activated (Xigris, Lilly), a recombinant form of protein C recently approved by the FDA for the treatment of severe sepsis, markedly reduces the risk of all-cause mortality in adult patients, according to findings from the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) clinical trial.
In this prospective, double-blind, placebo-controlled phase III study, a total of 1,690 patients with severe sepsis were randomized to placebo (840 patients) or drotreogin alfa activated 24 mcg/kg of body weight per hour administered intravenously at a constant rate for 96 hours. The primary endpoint of the study was all-cause mortality at 28 days. Patients were also monitored for results of microbiologic cultures, adverse events, changes in vital signs, and laboratory variables. Because the trial results met FDA criteria for efficacy among patients treated with drotre-ogin alfa (activated), trial enrollment was stopped in the middle of the study.
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At 28 days follow-up, administration of drotreogin alfa (activated) to patients with severe sepsis was associated with a statistically significant (19.4%) reduction in the relative risk of death compared to placebo, making this the first study of the treatment of severe sepsis to show such a difference. Further analysis of the data demonstrated that this beneficial treatment effect was independent of the type of bacterial pathogen.
In a comparison of all-cause, 28-day mortality rates by pathogen types (pure gram-positive, pure gram-negative, mixed gram-stain, pure fungal, and mixed bacterial and non-bacterial organisms) in subgroups with at least 150 patients, lower 28-day mortality rates were observed in the drotreogin alfa (activated) treatment group across the four most common pathogen classifications: unknown, pure gram-positive, pure gram-negative, and mixed gram bacterial.
Suppressive versus Episodic Therapy for Recurrent Genital Herpes
Speaker: Kenneth H. Fife, MD, PhD, Professor of Medicine, Microbiology & Immunology and Pathology, Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
New research suggests that managing recurrent genital herpes with 500 mg of oral valacyclovir (Valtrex tablet, GlaxoSmith Kline) daily as suppressive therapy—treating daily before symptoms ever appear—is significantly more effective at reducing the number of genital herpes recurrences, the time to first recurrence, and the percentage of patients who are recurrence-free at one year than treating with valacyclovir as episodic therapy (treating only as outbreaks occur).
Although valacyclovir has been shown to be effective for both acute treatment and chronic suppression of recurrent genital herpes, those treatment approaches have not been assessed to determine whether episodic or suppressive therapy is superior with regard to recurrence. In a randomized, open-label study, 80 otherwise healthy patients with a history of four to nine recurrences annually were randomly assigned to either episodic treatment with self-initiated, oral valacy-clovir 500 mg twice daily or suppressive treatment with 500 mg of oral valacyclovir canadian once daily, for one year. Patients maintained daily diaries, were evaluated monthly over the one-year study period, and completed quarterly quality-of-life surveys.
At the one-year follow-up, a total of 66 people (32 episodic and 34 suppressive) completed the study. Suppressive therapy with valacyclovir reduced the number of genital herpes outbreaks over the one-year study period by almost 80%, the average number of weeks to first recurrence being 4.7 days with episodic treatment and 23.27 days with suppressive therapy. Furthermore, 41% of patients receiving suppressive therapy did not experience an outbreak during the study compared to only 3% of those on episodic therapy. In addition, the mean number of days between recurrences of genital herpes was 179.8 days for patients on suppressive therapy, compared with 53 days between recurrences for those on episodic therapy. Overall, patients on suppressive therapy had a mean of 1.6 recurrences of genital herpes outbreaks versus 7.3 recurrences in those on episodic therapy. Finally, according to quality-of-life assessments, treatment with valacyclovir generic improved quality of life for all patients in the study.
