Archive for July 10, 2011

Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study

Plos Medicine May 2011

Molly F. Franke1,2*, James M. Robins1,3, Jules Mugabo4, Felix Kaigamba5, Lauren E. Cain1, Julia G. Fleming2, Megan B. Murray1,6

1 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Partners In Health, Boston, Massachusetts, United States of America, 3 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, 4 Center for Treatment and Research on AIDS, Malaria, Tuberculosis and Other Epidemics (TRAC Plus), Rwanda Ministry of Health, Kigali, Rwanda, 5 Ruhengeri Hospital, Rwanda Ministry of Health, Ruhengeri, Rwanda, 6 Division of Global Health Equity, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America

Background

Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART) in HIV-infected adults with sputum smear-positive tuberculosis (TB) disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting.

Methods and Findings

We retrospectively reviewed charts for 308 HIV-infected adults inRwandawith a CD4 count≤350 cells/µl and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1) death, default, or lost to follow-up and (2) death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95% confidence interval: [0.76, 0.89]) and 0.86 (95% confidence interval: [0.80, 0.92]), respectively. These were significantly higher than the probabilities computed under later start times. Results were similar for the endpoint of death, hospitalization, or serious opportunistic infection. cART initiation at day 15 versus later times was protective against death, default, or loss to follow-up, regardless of CD4 count. As with any observational study, the validity of these findings assumes that biases from residual confounding by unmeasured factors and from model misspecification are small.

Conclusions

Early cART reduced mortality among individuals with low CD4 counts and improved retention in care, regardless of CD4 count.

FULL TEXT

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001029

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July 10, 2011 at 10:27 pm Leave a comment

Invasive fungal infections: current perspectives on azole therapy

CURRENT OPINION in INFECTIOUS DISEASES AUG. 2011 V.24

 Invasive fungal infections: current perspectives on azole therapy

 website

http://journals.lww.com/co-infectiousdiseases/toc/2011/08002

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July 10, 2011 at 9:16 pm Leave a comment

The role of azoles in the treatment of invasive mycoses: review of the Infectious Diseases Society of America guidelines

Current Opinion in Infectious Diseases Aug. 2011

Pappas, Peter G

Abstract:

Purpose of review

The antifungal armamentarium for invasive mycoses has increased in recent years. Understanding the appropriate roles of standard and newer antifungals in the management of the various invasive mycoses encountered in clinical practice is critical for optimal patient care. This review examines the most current treatment guidelines from the Infectious Diseases Society of America for the management of patients with invasive mycoses with a focus on triazole therapies.

Recent findings

Voriconazole has emerged as the treatment of choice for most forms of invasive aspergillosis. Fluconazole remains the triazole of choice for most nonneutropenic patients with mild-to-moderate invasive candidiasis, whereas an echinocandin is preferred for those with moderate-to-severe illness or recent triazole therapy. An echinocandin or lipid formulation of amphotericin B is recommended for most neutropenic candidiasis patients, with fluconazole being considered an alternative for less critically ill patients with no recent triazole exposure. Voriconazole may be used to replace fluconazole in candidiasis patients with Candida krusei and fluconazole-resistant, voriconazole-susceptible isolates. Standard triazoles (fluconazole or itraconazole) are the cornerstone treatment for milder forms of endemic mycoses, whereas initial treatment with amphotericin B followed by step down therapy with fluconazole/itraconazole is the usual course for more serious endemic mycoses. Increasing evidence suggests voriconazole and posaconazole may play important roles in salvage therapy for central nervous system blastomycosis and cryptococcosis, respectively.

Summary

Standard triazoles continue to play a prominent role in the management of patients with invasive mycoses. Newer triazoles are beginning to gain a foothold in particular mycoses or subsets of patients, but more research is needed to better define the place of these broad-spectrum triazoles in the treatment of invasive mycoses.

abstract

http://journals.lww.com/co-infectiousdiseases/toc/2011/08002

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July 10, 2011 at 9:15 pm Leave a comment

Azoles: back to the future

Current Opinion in Infectious Diseases. Aug 2011

Perfect, John R

Abstract:

Purpose of review

Azoles are among the oldest class of antifungals, and they continue to be integral to the treatment of invasive fungal infections. This review examines the place of azoles in the treatment of invasive candidiasis and aspergillosis, and their use in the management of diseases caused by rare but emerging opportunistic molds.

Recent findings

Standard azoles have utility as prophylaxis for invasive candidiasis and posaconazole for prophylaxis of invasive aspergillosis in high-risk patients, but the optimal conditions for prophylaxis deployment are still being investigated. Standard azoles are important for initial treatment or as step-down therapy for candidemia and voriconazole for initial treatment of aspergillosis. There is hope that nonculture-based microbiological tools enabling detection of biomarkers for candidemia or aspergillosis may lead to earlier intervention and improved outcomes for these infections. The newer triazoles with broader-spectrum activity may be helpful in the management of a variety of diseases associated with non-Aspergillus molds such as fusariosis, scedosporiosis, and phaeohyphomycosis. Posaconazole, but not voriconazole, is also active against disease-causing zygomycetes.

Summary

The role of azoles in the management of serious invasive fungal infections continues to evolve, with ongoing research further defining and broadening their uses. It is critical that clinicians stay abreast of the latest data supporting the current and evolving roles of these important agents.

abstract

http://journals.lww.com/co-infectiousdiseases/toc/2011/08002

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July 10, 2011 at 9:14 pm Leave a comment

Invasive fungal infections: current perspectives on azole therapy

Curent Opinion in ID Aug 2011

Abstract:

Purpose of review

The antifungal armamentarium for invasive mycoses has increased in recent years. Understanding the appropriate roles of standard and newer antifungals in the management of the various invasive mycoses encountered in clinical practice is critical for optimal patient care. This review examines the most current treatment guidelines from the Infectious Diseases Society of America for the management of patients with invasive mycoses with a focus on triazole therapies.

Recent findings

Voriconazole has emerged as the treatment of choice for most forms of invasive aspergillosis. Fluconazole remains the triazole of choice for most nonneutropenic patients with mild-to-moderate invasive candidiasis, whereas an echinocandin is preferred for those with moderate-to-severe illness or recent triazole therapy. An echinocandin or lipid formulation of amphotericin B is recommended for most neutropenic candidiasis patients, with fluconazole being considered an alternative for less critically ill patients with no recent triazole exposure. Voriconazole may be used to replace fluconazole in candidiasis patients with Candida krusei and fluconazole-resistant, voriconazole-susceptible isolates. Standard triazoles (fluconazole or itraconazole) are the cornerstone treatment for milder forms of endemic mycoses, whereas initial treatment with amphotericin B followed by step down therapy with fluconazole/itraconazole is the usual course for more serious endemic mycoses. Increasing evidence suggests voriconazole and posaconazole may play important roles in salvage therapy for central nervous system blastomycosis and cryptococcosis, respectively.

Summary

Standard triazoles continue to play a prominent role in the management of patients with invasive mycoses. Newer triazoles are beginning to gain a foothold in particular mycoses or subsets of patients, but more research is needed to better define the place of these broad-spectrum triazoles in the treatment of invasive mycoses.

abstract

http://journals.lww.com/co-infectiousdiseases/toc/2011/08002

PDF (hacer CLIC en PDF) FREE

July 10, 2011 at 9:12 pm Leave a comment


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