Archive for December, 2011
Comparative Effectiveness of Clostridium difficile Treatments
Annals of Internal Medicine 20 Dec 2011 V.155 N.12 P.839-847
A Systematic Review
Dimitri M. Drekonja, MD, MS; Mary Butler, PhD, MBA; Roderick MacDonald, MS; Donna Bliss, PhD, RN; Gregory A. Filice, MD; Thomas S. Rector, PhD; and Timothy J. Wilt, MD, MPH
From Minneapolis Veterans Affairs Health Care System, University of Minnesota Medical School, Minnesota Evidence-based Practice Center, University of Minnesota School of Public Health, and University of Minnesota School of Nursing, Minneapolis, Minnesota.
Abstract
Background
Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown.
Purpose
To determine whether, among adults with C. difficile infection, treatment with certain antibiotics compared with others results in differences in initial cure, recurrence, and harms.
Data Sources
MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review.
Study Selection
Randomized, controlled trials of adults with C. difficile infection, independent of outcomes, who were treated with medications available in theUnited States. Observational studies reporting strain were included.
Data Extraction
Study design, inclusion and exclusion criteria, quality and strength of evidence as assessed by 2 reviewers, study definitions, and duration of treatment and follow-up. Outcomes included initial cure, recurrence, and treatment harms.
Data Synthesis
11 trials that included 1463 participants were identified. Three trials compared metronidazole with vancomycin; 8 compared metronidazole or vancomycin with another agent, combined agents, or placebo. Strain was analyzed in 1 trial and 2 cohort studies. No study comparing 2 antimicrobial agents demonstrated a statistically significant difference for initial cure; all comparisons were of low to moderate strength of evidence. Moderate-strength evidence from 1 study demonstrated that recurrence was decreased with fidaxomicin versus vancomycin (15% vs. 25%; difference, −10 percentage points [95% CI, −17 to −3 percentage points]; P = 0.005). Subgroup analysis of a single study comparing metronidazole with vancomycin for patients who have severe C. difficile infection showed no difference by intention-to-treat analysis; this was rated as insufficient-strength evidence. Harms, when reported, did not differ between treatments in any study.
Limitations
Definitions of diarrhea, C. difficile infection, initial cure, and relapse varied. Some studies reported insufficient detail to allow assessment of all randomly assigned participants or of harms.
Conclusion
No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin.
Primary Funding Source
U.S.Department of Health and Human Services.
Abstract
http://www.annals.org/content/155/12/839.abstract
http://www.annals.org/content/155/12/839.full.pdf+html
Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV Type-1: A Randomized Trial
Ann of Int Med 05 Apr 2011 V.154 N.7 P.445-456
Eric S. Daar, Camlin Tierney, Margaret A. Fischl, Paul E. Sax, Katie Mollan, Chakra Budhathoki, Catherine Godfrey, Nasreen C. Jahed, Laurie Myers, David Katzenstein, Awny Farajallah, James F. Rooney, Keith A. Pappa,William C. Woodward, Kristine Patterson, Hector Bolivar, Constance A. Benson, Ann C. Collier for the AIDS Clinical Trials Group Study A5202 Team
From Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of California, Los Angeles, Los Angeles, California; Harvard School of Public Health, Boston, Massachusetts; University of Miami School of Medicine, Miami, Florida; Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; Social and Scientific Systems, Silver Spring, Maryland; Frontier Science and Technology Research Foundation, Amherst, New York; Stanford University, Palo Alto, California; Bristol-Myers Squibb, Plainsboro, New Jersey; Gilead Sciences, Foster City, California; GlaxoSmithKline, Research Triangle Park, North Carolina; Abbott Laboratories, Abbott Park, Illinois; University of North Carolina, Chapel Hill, North Carolina; University of California, San Diego, San Diego, California; and University of Washington and Harborview Medical Center, Seattle, Washington.
Background
Limited data compare once-daily options for initial therapy for HIV type 1 (HIV-1).
Objective
To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.
Design
A randomized equivalence trial conducted from September 2005 to November 2007, with a median 138 weeks follow-up. Regimens assigned by central computer, stratified by screening HIV-1 RNA less than 100 000 copies/mL or 100 000 copies/mL or more, with blinding only known to the site pharmacist (ClinicalTrials.gov registration number: NCT00118898).
Setting
59 AIDS Clinical Trials Group sites in theUnited StatesandPuerto Rico.
Patients
Antiretroviral-naïve patients.
Intervention
Open-label atazanavir plus ritonavir or efavirenz with placebo-controlled abacavir–lamivudine or tenofovir disoproxil fumarate (DF)–emtricitabine.
Measurements
Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion with HIV-1 RNA less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.
Results
Eligible patients randomly assigned to atazanavir plus ritonavir versus efavirenz with abacavir–lamivudine were 463 and 465, with 322 (70%) and 324 (70%) completing follow-up, respectively. Total participants who received tenofovir DF–emtricitabine were 465 and 464, with 342 (74%) and 343 (74%) completing follow-up, respectively. Primary efficacy was similar between the groups who received atazanavir plus ritonavir and efavirenz with abacavir–lamivudine or tenofovir DF–emtricitabine. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively; although CIs did not meet prespecified criteria for equivalence. There was a longer time to safety (P = 0.048) and tolerability (P < 0.001) events in persons given atazanavir plus ritonavir than efavirenz with abacavir–lamivudine but not with tenofovir DF–emtricitabine.
Limitations
Neither HLA-B*5701 or resistance testing were the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz were open-label, the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum, and 32% of patients modified or discontinued their third drug.
Conclusion
Atazanavir plus ritonavir and efavirenz provide similar antiviral activity when used with abacavir–lamivudine or tenofovir DF–emtricitabine.
Abstract
http://www.annals.org/content/early/2011/02/11/0003-4819-154-7-201104050-00316.abstract?papetoc
FULL TEXT
http://www.annals.org/content/early/2011/02/11/0003-4819-154-7-201104050-00316.full
Thirty Years of HIV and AIDS: Future Challenges and Opportunities
Ann Int Med 07 June May 2011 V,154 N.11 P.766-771
Carl W. Dieffenbach and Anthony S. Fauci
From the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Abstract
As the third decade since AIDS was first recognized comes to an end, extraordinary advances have occurred in the understanding, treatment, and prevention of HIV infection and AIDS. As a result of these successes, it is now time to focus on future challenges.Paramountamong these is reaching the goal of truly controlling and ultimately ending the HIV and AIDS pandemic.
To that end, AIDS researchers and public health personnel worldwide are aggressively pursuing 3 key areas of scientific research. Given the availability of highly effective therapeutic regimens for HIV infection, the first challenge is efficiently identifying a maximum number of HIV-infected persons through voluntary HIV testing and initiating antiretroviral therapy (ART). Second, scientists are trying to develop a cure for HIV infection, which would alleviate the need for lifelong ART. Finally, preventing new cases of HIV infection, which currently number approximately 2.6 million per year globally, is critical to any attempt to end this pandemic. This article addresses each of these challenges and provides directions for the future.
Abstract
http://www.annals.org/content/early/2011/05/27/0003-4819-154-11-201106070-00345.abstract?papetoc
http://www.annals.org/content/early/2011/05/27/0003-4819-154-11-201106070-00345.full.pdf+html
Guillain–Barré Syndrome following Primary Cytomegalovirus Infection: A Prospective Cohort Study
Clinical Infect Diseases Apr.1, 2011 V.52 N.6 P.837-844
David Orlikowski1,4, Raphaël Porcher5,6, Valérie Sivadon-Tardy4,10, Jean-Charles Quincampoix4,10, Jean-Claude Raphaël1,4,*, Marie-Christine Durand2, Tarek Sharshar1,4, Jacqueline Roussi3,4, Christiane Caudie11, Djillali Annane1,4, Flore Rozenberg7,8, Marianne Leruez-Ville8,9, Jean-Louis Gaillard4,10, and Elyanne Gault4,10
1Service de Réanimation
2Service de Physiologie et Explorations Fonctionnelles
3Service d’Hématologie Immunologie, AP-HP, Hôpital Raymond Poincaré, Garches
4Université de Versailles St-Quentin-en-Yvelines, UPRES EA4342, Guyancourt
5AP-HP, Hôpital St-Louis, Département de Biostatistique et Informatique Médicale, Paris
6Université Paris Diderot Paris 7, Inserm U717
7AP-HP, Hôpital Cochin-St-Vincent-de-Paul, Laboratoire de Virologie, Paris
8Université Paris Descartes Paris 5
9AP-HP, Hôpital Necker, Laboratoire de Virologie, Paris
10AP-HP, Hôpital Ambroise Paré, Laboratoire de Microbiologie, Boulogne-Billancourt
11Hôpital Neurologique de Lyon, Fédération de Biologie, Service d’Immunologie, Bron, France
Background
Little is known about the epidemiology and the prognostic factors of Guillain–Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS).
Methods
We prospectively followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher’s exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods.
Results
Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P = .052). The main factors associated with long-term neurological sequelae (21%) were older age (P < .001) and assisted ventilation during hospitalization (P = .005). The number of CMV-GBS cases decreased between 1996 and 2006 (P = .019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection).
Conclusions
This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.
abstract
http://cid.oxfordjournals.org/content/52/7/837.abstract
http://cid.oxfordjournals.org/content/52/7/837.full.pdf+html
Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America
Clinical Infect Diseases Feb.15, 2011 V.52 N.4 P.427-431
Executive Summary
Alison G. Freifeld1, Eric J. Bow9, Kent A. Sepkowitz2, Michael J. Boeckh4, James I. Ito5, Craig A. Mullen3, Issam I. Raad6, Kenneth V. Rolston6, Jo-Anne H. Young7, and John R. Wingard8
1Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska
2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York
3Department of Pediatrics, University of Rochester Medical Center, Rochester, New York
4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research, Seattle, Washington
5Division of Infectious Diseases, City of Hope National Medical Center, Duarte, California
6Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
7Department of Medicine, University of Minnesota, Minneapolis, Minnesota
8Division of Hematology/Oncology, University of Florida, Gainesville, Florida
9Departments of Medical Microbiology and Internal Medicine, the University of Manitoba, and Infection Control Services, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia.
Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving.
What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens.
Finally, we note that all Panel members are from institutions in theUnited StatesorCanada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside ofNorth America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care–associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
abstract
http://cid.oxfordjournals.org/content/52/4/427.abstract
http://cid.oxfordjournals.org/content/52/4/427.full.pdf+html
- – -
Clinical Infect Diseases Feb.15, 2011 V.52 N.4 P.e56-e93
Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America
Alison G. Freifeld1, Eric J. Bow9, Kent A. Sepkowitz2, Michael J. Boeckh4, James I. Ito5, Craig A. Mullen3, Issam I. Raad6, Kenneth V. Rolston6, Jo-Anne H. Young7, and John R. Wingard8
1Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska
2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York
3Department of Pediatrics, University of Rochester Medical Center, Rochester, New York
4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research, Seattle, Washington
5Division of Infectious Diseases, City of Hope National Medical Center, Duarte, California
6Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
7Department of Medicine, University of Minnesota, Minneapolis, Minnesota
8Division of Hematology/Oncology, University of Florida, Gainesville, Florida
9Departments of Medical Microbiology and Internal Medicine, the University of Manitoba, and Infection Control Services, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia.
Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving.
What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens.
Finally, we note that all Panel members are from institutions in theUnited StatesorCanada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside ofNorth America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care–associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
abstract
http://cid.oxfordjournals.org/content/52/4/e56.abstract
http://cid.oxfordjournals.org/content/52/4/e56.full.pdf+html
Methodologies for evaluating HIV prevention intervention (populations and epidemiologic settings).
Curr Opin HIV AIDS. 2009 Jul;4(4):274-8.
Gray RH.
Source
Reproductive Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, E4132, 615 N Wolfe Street, Baltimore, MD 21205, USA. rgray@jhsph.edu
Abstract
PURPOSE OF REVIEW:
There have been over 30 HIV-prevention trials of which only four reported evidence of efficacy. The reasons for these negative findings may be due to ineffective interventions, but in part reflect the inappropriate selection of study populations and epidemiologic settings.
RECENT FINDINGS:
Three trials showed that male circumcision reduces HIV acquisition in men by 50-60%. In contrast, seven out of eight trials of bacterial and viral sexually transmitted infection (STI) control, and multiple microbicide trials show no efficacy for HIV prevention. Several microbicide trials found vaginal irritation and microulceration, which may increase HIV risk. Three vaccine trials failed to show efficacy and one trial suggested increased HIV risk in a subgroup of uncircumcised men.
SUMMARY:
The failure of most prevention trials reflects inadequate pretrial screening of potentially efficacious interventions, insufficient information on background HIV incidence, selection of high-risk populations with poor compliance and lack of generalizability, and treatment interruption during pregnancy all of which compromise power.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883269/pdf/nihms202778.pdf
Update: Influenza A (H3N2)v Transmission and Guidelines — Five States, 2011
MMWR Dec.23, 2011 V.60 Early Release P.1-4
As of December 23, 2011, CDC had received reports of 12 human infections with influenza A (H3N2)v viruses that have the matrix (M) gene from the influenza A (H1N1)pdm09 virus (formerly called swine-origin influenza A [H3N2] and pandemic influenza A [H1N1] 2009 viruses, respectively). The 12 cases occurred in five states (Indiana,Iowa,Maine,Pennsylvania, andWest Virginia), and 11 were in children. This report describes those cases and swine influenza virus (SIV) surveillance being conducted by the U.S. Department of Agriculture.
FULL TEXT
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm60e1223a1.htm?s_cid=mm60e1223a1_e
