Archive for September 24, 2010

Comparison of Changes in Bone Density and Turnover with Abacavir-Lamivudine versus Tenofovir-Emtricitabine in HIV-Infected Adults: 48-Week Results from the ASSERT Study

Clinical Infectious Diseases 15 Oct 2010 V.51  N.8 p.963–972

 Hans-Jürgen Stellbrink,1 Chloe Orkin,2 Jose Ramon Arribas,6 Juliet Compston,5 Jan Gerstoft,7 Eric Van Wijngaerden,8 Adriano Lazzarin,9 Giuliano Rizzardini,10 Herman G. Sprenger,11 John Lambert,12 Gunta Sture,13 David Leather,3 Sara Hughes,4 Patrizia Zucchi,14 and Helen Pearce,3 on behalf of the ASSERT Study Group

1Infektions Medizinisches Centrum Hamburg Study Center, Hamburg, Germany; 2St Bartholomew’s Hospital, 3GlaxoSmithKline, and 4ViiV Healthcare, London, and 5University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; 6Instituto de Investigacion (IdiPAZ), Hospital La Paz, Madrid, Spain; 7Rigshospitalet, Copenhagen, Denmark; 8UZ Leuven, Leuven, Belgium; 9Ospedale San Raffaele and 10Ospedale Luigi Sacco, Milan, Italy; 11University Medical Center Groningen, Groningen, the Netherlands; 12Mater Misericordiae University Hospital and University College Dublin, Dublin, Ireland; 13Latvijas Infektologijas Centrs, Riga, Latvia; and 14GlaxoSmithKline, Verona, Italy

Background

Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles.

Methods

In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir-emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis.

Results

A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, −1.9%; tenofovir-emtricitabine group, −3.6%;  ) and lumbar spine (abacavir-lamivudine group, −1.6%; tenofovir-emtricitabine group, −2.4%;  ). BMD loss of 6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of 6% in the hip; 15% vs 5% had a loss of 6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofovir-emtricitabine group, +11.92 mg/L;  ).

Conclusions

This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.

abstract

http://www.journals.uchicago.edu/doi/abs/10.1086/656417

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/656417

 

EDITORIAL COMMENTARY

Low Bone Mineral Density with Tenofovir: Does Statistically Significant Mean Clinically Significant?

Andrew Carr1 and  Jennifer Hoy2

1HIV, Immunology and Infectious Diseases Unit and Centre for Applied Medical Research, St Vincent’s Hospital, University of New South Wales, Sydney, and 2Infectious Diseases Unit, Alfred Hospital and Monash University, Melbourne, Australia

FULL TEXT

http://www.journals.uchicago.edu/doi/full/10.1086/656418

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/656418

September 24, 2010 at 11:34 am Leave a comment

Skin and Soft-Tissue Infections Requiring Hospitalization at an Academic Medical Center: Opportunities for Antimicrobial Stewardship

Clinical Infectious Diseases 15 Oct 2010 V.51  N.8 p.895-903

Timothy C. Jenkins,1,4 Allison L. Sabel,3,5 Ellen E. Sarcone,2,4 Connie S. Price,1,4 Philip S. Mehler,2,3,4 and William J. Burman1,4

1Department of Medicine and Division of Infectious Diseases, 2Department of Medicine, and 3Department of Patient Safety and Quality, Denver Health Medical Center, and Departments of 4Medicine and 5Preventive Medicine and Biometry, University of Colorado Denver, Denver

Background

Although complicated skin and soft-tissue infections (SSTIs) are among the most common infections requiring hospitalization, their clinical spectrum, management, and outcomes have not been well described.

Methods

We report a cohort of consecutive adult patients hospitalized for SSTI from 1 January through 31 December 2007 at an academic medical center. Cases meeting inclusion criteria were reviewed and classified as cellulitis, cutaneous abscess, or SSTI with additional complicating factors.

Results

In total, 322 patients were included; 66 (20%) had cellulitis, 103 (32%) had cutaneous abscess, and 153 (48%) had SSTI with additional complicating factors. Injection drug use, diabetes mellitus, and alcohol abuse were common comorbidities. Serum inflammatory markers were routinely measured and blood cultures and imaging studies were routinely performed in each group. Of 150 patients with a positive culture result for an abscess, deep tissue, or blood, Staphylococcus aureus or streptococci were identified in 145 (97%). Use of antibiotics with broad aerobic gram-negative activity (61%–80% of patients) or anaerobic activity (73%–83% of patients) was frequent in each group. The median duration of therapy for cellulitis, cutaneous abscess, and SSTI with additional complicating factors was 13 (interquartile range [IQR], 10–14), 13 (IQR, 10–16), and 14 (IQR, 11–17) days, respectively. Treatment failure, recurrence, or rehospitalization due to SSTI within 30 days occurred in 12.1%, 4.9%, and 9.2% of patients, respectively.

Conclusions

Hospitalizations for SSTI were common; more than half were due to cellulitis or cutaneous abscess. Frequent use of potentially unnecessary diagnostic studies, broad-spectrum antibiotic therapy, and prolonged treatment courses in these patients suggest targets for antimicrobial stewardship programs.

abstract

http://www.journals.uchicago.edu/doi/abs/10.1086/656431

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/656431

EDITORIAL COMMENTARY

Skin and Soft-Tissue Infections: Modern Evolution of an Ancient Problem

Brad Spellberg

Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor–University of California at Los Angeles (UCLA) Medical Center, Torrance, and David Geffen School of Medicine at UCLA, Los Angeles

FULL TEXT

http://www.journals.uchicago.edu/doi/full/10.1086/656432

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/656432

September 24, 2010 at 11:31 am Leave a comment

Update: Detection of a Verona Integron-Encoded Metallo-Beta-Lactamase in Klebsiella pneumoniae — United States, 2010

MMWR Early Release  Sept 21, 2010 V.59  N.37 p.1212 Early Release

In July, CDC learned of a patient with a carbapenem-resistant Klebsiella pneumoniae strain that produced a Verona integron-encoded metallo-beta-lactamase carbapenemase not reported previously among Enterobacteriaceae in the United States. The patient became ill during a cruise and was first hospitalized in Greece and then in the United States. Testing showed the isolate to be nonsusceptible to all antimicrobials usually used to treat Klebsiella. Despite this resistance, the patient recovered sufficiently to be discharged after 26 days in the U.S. hospital. This report follows a June report of three cases of New Delhi metallo-beta-lactamase–producing Enterobacteriaceae. However, the most common mechanism of carbapenem resistance among Enterobacteriaceae in the United States remains production of the Klebsiella pneumoniae carbapenemase.

FULL TEXT

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5937a4.htm?s_cid=mm5937a4_w

PDF

http://www.cdc.gov/mmwr/pdf/wk/mm5937.pdf

September 24, 2010 at 11:28 am Leave a comment


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