Archive for September 17, 2011

National guidelines for decolonization of methicillin-resistant Staphylococcus aureus carriers: the implications of recent experience in the Netherlands

Journal of Antimicrobial Chemotherapy October 2011 V.66 N.10 P.2195-2198

Evelina Tacconelli1,* and Alan P. Johnson2

1Department of Infectious Disease, Università Cattolica, largo F. Vito 1, 00168, Rome, Italy

2Department of Healthcare-associated Infections and Antimicrobial Resistance, Health Protection Agency Centre for Infections, London NW9 5EQ, UK

Abstract

Screening of patients for carriage of methicillin-resistant Staphylococcus aureus (MRSA) coupled with interventions such as contact isolation is widely regarded as a means of reducing rates of MRSA infection and inter-patient transmission. Recent studies in the Netherlands have shown that introduction of a national guideline in which uncomplicated carriage is treated with mupirocin nasal ointment and chlorhexidine soap solution, and complicated carriage is treated using the same regimen supplemented with two oral antibiotics, was successful, with up to 80% of patients being decolonized. Increased success was seen in patients, particularly those with complicated carriage, whose treatment adhered closely to the guideline. As the Netherlands has a low level of MRSA, further work is required to see if this regimen will be as effective at reducing carriage in countries with higher rates of endemic MRSA, where re-colonization may be expected to occur more often.

abstract

http://jac.oxfordjournals.org/content/66/10/2195.abstract

PDF

http://jac.oxfordjournals.org/content/66/10/2195.full.pdf+html

September 17, 2011 at 12:09 pm Leave a comment

Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection

N Engl J of Medic 15 September 2011 V.365  P.1014-1024

Kenneth E. Sherman, M.D., Ph.D., Steven L. Flamm, M.D., Nezam H. Afdhal, M.D., David R. Nelson, M.D., Mark S. Sulkowski, M.D., Gregory T. Everson, M.D., Michael W. Fried, M.D., Michael Adler, M.D., Ph.D., Hendrik W. Reesink, M.D., Ph.D., Marie Martin, Ph.D., Abdul J. Sankoh, Ph.D., Nathalie Adda, M.D., Robert S. Kauffman, M.D., Ph.D., Shelley George, M.D., Christopher I. Wright, M.D., Ph.D., and Fred Poordad, M.D. for the ILLUMINATE Study Team

From the Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati (K.E.S.); the Division of Hepatology, Northwestern University Medical School, Chicago (S.L.F.); the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston (N.H.A.); the Section of Hepatology, University of Florida, Gainesville (D.R.N.); the Viral Hepatitis Center, Johns Hopkins University School of Medicine, Baltimore (M.S.S.); the Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine Denver, Aurora (G.T.E.); the UNC Liver Center, University of North Carolina, Chapel Hill (M.W.F.); the Department of Gastroenterology and Hepatopancreatology, Erasme Hospital Brussels, Brussels (M.A.); the Department of Hepatology, Academic Medical Center of the University of Amsterdam, Amsterdam (H.W.R.); Vertex Pharmaceuticals, Cambridge,

MA (M.M., A.J.S., N.A., R.S.K., S.G., C.I.W.); and the Department of Medicine, Cedars–Sinai Medical Center, Los Angeles (F.P.).

Background

Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon–ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, −10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.

Methods

We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon–ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.

Results

Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, −2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001).

Conclusions

In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon–ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.)

abstract

http://www.nejm.org/doi/full/10.1056/NEJMoa1014463?query=TOC

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1014463

September 17, 2011 at 12:06 pm Leave a comment

A Field Trial to Assess a Blood-Stage Malaria Vaccine

N Engl J of Medic 15 September 2011 V.365 N.6 P.1004-1013

Mahamadou A. Thera, M.D., M.P.H., Ogobara K. Doumbo, M.D., Ph.D., Drissa Coulibaly, M.D., Matthew B. Laurens, M.D., M.P.H., Amed Ouattara, Pharm.D., Abdoulaye K. Kone, M.D., Ando B. Guindo, M.D., Karim Traore, M.D., Idrissa Traore, M.D., Bourema Kouriba, Pharm.D., Ph.D., Dapa A. Diallo, M.D., Issa Diarra, Pharm.D., Modibo Daou, Pharm.D., Amagana Dolo, Pharm.D., Ph.D., Youssouf Tolo, Pharm.D., Mahamadou S. Sissoko, M.D., M.S.P.H., Amadou Niangaly, Pharm.D., Mady Sissoko, Pharm.D., Shannon Takala-Harrison, Ph.D., Kirsten E. Lyke, M.D., Yukun Wu, Ph.D., William C. Blackwelder, Ph.D., Olivier Godeaux, M.D., Johan Vekemans, M.D., Ph.D., Marie-Claude Dubois, M.Sc., W. Ripley Ballou, M.D., Joe Cohen, Ph.D., Darby Thompson, M.S., Tina Dube, Ph.D., Lorraine Soisson, Ph.D., Carter L. Diggs, M.D., Ph.D., Brent House, Ph.D., David E. Lanar, Ph.D., Sheetij Dutta, Ph.D., D. Gray Heppner, Jr., M.D., and Christopher V. Plowe, M.D., M.P.H.

From the Malaria Research and Training Center, University of Bamako, Bamako, Mali (M.A.T., O.K.D., D.C., A.O., A.K.K., A.B.G., K.T., I.T., B.K., D.A.D., I.D., M.D., A.D., Y.T., M.S.S., A.N., M.S.); Howard

Hughes Medical Institute and Center for Vaccine Development at the University of Maryland School of Medicine, Baltimore (M.B.L., A.O., S.T.-H., K.E.L., Y.W., W.C.B., C.V.P.); GlaxoSmithKline Biologicals, Rixensart, Belgium (O.G., J.V., M.-C.D., W.R.B., J.C.); EMMES, Rockville, MD (D.T., T.D.); the Malaria Vaccine Development Program, U.S. Agency for International Development, Washington, DC (L.S., C.L.D.); and Walter Reed Army Institute of Research, Silver Spring, MD (B.H., D.E.L., S.D., D.G.H.).

Address reprint requests to Dr. Plowe at Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1-480, Baltimore, MD 21201,

or at cplowe@medicine.umaryland.edu

Background

Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children

Methods

In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain.

Results

The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine.

Conclusions

On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.)

abstract

http://www.nejm.org/doi/full/10.1056/NEJMoa1008115?query=TOC

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1008115

September 17, 2011 at 12:03 pm Leave a comment


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