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Title: Independent association between rate of clearance of infection and clinical outcome of hiv-associated cryptococcal meningitis: Analysis of a combined cohort of 262 patients
Authors: Tihan A. Bicanic
Conrad Muzoora
Annemarie E. Brouwer
Graeme Meintjes
Nicky Longley
Kabanda Taseera
Kevin Rebe
Angela Loyse
Joseph Jarvis
Linda Gail Bekker
Robin Wood
Direk Limmathurotsakul
Wirongrong Chierakul
Kasia Stepniewska
Nicholas J. White
Shabbar Jaffar
Thomas S. Harrison
St George's University of London
University of Oxford
Nuffield Department of Clinical Medicine
Institute of Infectious Disease and Molecular Medicine
University of Cape Town
GF Jooste Hospital
Mbarara University of Science and Technology
Radboud University Nijmegen Medical Centre
Mahidol University
Keywords: Medicine
Issue Date: 1-Sep-2009
Citation: Clinical Infectious Diseases. Vol.49, No.5 (2009), 702-709
Abstract: Background. Progress in therapy for cryptococcal meningitis has been slow because of the lack of a suitable marker of treatment response. Previously, we demonstrated the statistical power of a novel endpoint, the rate of clearance of infection, based on serial quantitative cultures of cerebrospinal fluid, to differentiate the fungicidal activity of alternative antifungal drug regimens. We hypothesized that the rate of clearance of infection should also be a clinically meaningful endpoint. Methods. We combined data from cohorts of patients with human immunodeficiency virus-associated cryptococcal meningitis from Thailand, South Africa, and Uganda, for whom the rate of clearance of infection was determined, and clinical and laboratory data prospectively collected, and explored the association between the rate of clearance of infection and mortality by Cox survival analyses. Results. The combined cohort comprised 262 subjects. Altered mental status at presentation, a high baseline organism load, and a slow rate of clearance of infection were independently associated with increased mortality at 2 and 10 weeks. Rate of clearance of infection was associated with antifungal drug regimen and baseline cerebrospinal fluid interferon-7 levels. Conclusions. The results support the use of the rate of clearance of infection or early fungicidal activity as a means to explore antifungal drug dosages and combinations in phase II studies. An increased understanding of how the factors determining outcome interrelate may help clarify opportunities for intervention. © 2009 by the Infectious Diseases Society of America. All rights reserved.
ISSN: 10584838
Appears in Collections:Scopus 2006-2010

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