Publication: Independent association between rate of clearance of infection and clinical outcome of hiv-associated cryptococcal meningitis: Analysis of a combined cohort of 262 patients
Issued Date
2009-09-01
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10584838
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2-s2.0-70149095995
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Infectious Diseases. Vol.49, No.5 (2009), 702-709
Suggested Citation
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 Independent association between rate of clearance of infection and clinical outcome of hiv-associated cryptococcal meningitis: Analysis of a combined cohort of 262 patients. Clinical Infectious Diseases. Vol.49, No.5 (2009), 702-709. doi:10.1086/604716 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27979
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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
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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.