Archive for December 2, 2016

Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Infectious Diseases February 15, 2016 V.62 N.4 P.468-476

James Whitehorn, Chau Van Vinh Nguyen, Lam Phung Khanh, Duong Thi Hue Kien, Nguyen Than Ha Quyen, Nguyen Thi Thanh Tran, Nguyen Thuy Hang, Nguyen Thanh Truong, Luong Thi Hue Tai, Nguyen Thi Cam Huong, Vo Thanh Nhon, Ta Van Tram, Jeremy Farrar, Marcel Wolbers, Cameron P. Simmons, and Bridget Wills

1London School of Hygiene and Tropical Medicine, United Kingdom

2Oxford University Clinical Research Unit

3Hospital for Tropical Diseases, Ho Chi Minh City

4Tien Giang Hospital, My Tho, Vietnam

5Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom

6Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Victoria, Australia

Dengue is a viral disease for which there is currently no therapeutic agent. We investigated the potential of lovastatin in the treatment of dengue. Lovastatin was safe and well tolerated, but did not demonstrate a therapeutic benefit.

Background

Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy.

Methods

Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms.

Results

Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures.

Conclusions

We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.

Chinese Clinical Trials Registration.ISRCTN03147572.

PDF

http://cid.oxfordjournals.org/content/62/4/468.full.pdf

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December 2, 2016 at 9:29 am

Transmission of carbapenem-resistant pathogens in New York City hospitals: progress and frustration

Journal of Antimicrobial Chemotherapy JUNE 2012 V.97  N.6  P.1427-1431

David Landman, Elizabeth Babu, Neha Shah, Paul Kelly, Olafisoye Olawole, Martin Bäcker, Simona Bratu, and John Quale

Division of Infectious Diseases, Department of Medicine, State University of New York–Downstate Medical Center, Brooklyn, New York, USA

Objectives

Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are endemic in many medical centres. Because therapeutic options are limited, understanding the epidemiology and controlling the spread of these pathogens are of paramount importance.

Methods

Isolates of K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in New York City over a 3 month period in 2009, and analysed for the presence of genes encoding important carbapenemases. Comparisons were made with a similar study conducted in 2006. Demographic and infection control-related information from hospitals was collected.

Results

Overall, 29% of K. pneumoniae possessed the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P<0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the hospitals. In a subset analysis of nine hospitals, those with a decreasing prevalence of blaKPC had shorter average lengths of stay.

Conclusions

Measurable improvement has occurred in reducing the spread of KPC-possessing K. pneumoniae, and reducing the average length of stay may augment infection control efforts. However, the problem of carbapenem-resistant A. baumannii and P. aeruginosa lingers. New approaches, including respiratory isolation and environmental cleaning, need to be examined to control the spread of A. baumannii and P. aeruginosa.

PDF

http://jac.oxfordjournals.org/content/67/6/1427.full.pdf

December 2, 2016 at 9:27 am


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