Determinants of Mortality in a Combined Cohort of 501 Patients With HIV-Associated Cryptococcal Meningitis: Implications for Improving Outcomes

被引：283

作者：

Jarvis, Joseph N. ^{[1
,2
,3
,4
]}

Bicanic, Tihana ^{[1
]}

Loyse, Angela ^{[1
]}

Namarika, Daniel ^{[5
]}

Jackson, Arthur ^{[5
]}

Nussbaum, Jesse C. ^{[5
,6
]}

Longley, Nicky ^{[1
,2
,4
]}

Muzoora, Conrad ^{[7
]}

Phulusa, Jacob ^{[5
]}

Taseera, Kabanda ^{[7
]}

Kanyembe, Creto ^{[5
]}

Wilson, Douglas ^{[8
]}

Hosseinipour, Mina C. ^{[5
]}

Brouwer, Annemarie E. ^{[9
,10
]}

Limmathurotsakul, Direk ^{[11
]}

White, Nicholas ^{[11
,12
]}

van der Horst, Charles ^{[5
]}

Wood, Robin ^{[2
]}

Meintjes, Graeme ^{[4
,13
,14
]}

Bradley, John ^{[15
]}

Jaffar, Shabbar ^{[15
]}

Harrison, Thomas ^{[1
]}

机构：

[1] St Georges Univ London, Div Clin Sci, Res Ctr Infect & Immun, London, England

[2] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7700 Rondebosch, South Africa

[3] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Clin Res, London WC1E 7HT, England

[4] Univ Cape Town, Dept Med, Div Infect Dis & HIV Med, ZA-7700 Rondebosch, South Africa

[5] Univ North Carolina Project, Lilongwe, Malawi

[6] Univ Calif San Francisco, Dept Infect Dis, San Francisco, CA 94143 USA

[7] Mbarara Univ Sci & Technol, Mbarara, Uganda

[8] Edendale Hosp, Pietermaritzburg, South Africa

[9] St Elisabeth Hosp Tilburg, Tilburg, Netherlands

[10] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands

[11] Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand

[12] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England

[13] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa

[14] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England

[15] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England

来源：

CLINICAL INFECTIOUS DISEASES | 2014年 / 58卷 / 05期

基金：

美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会;

关键词：

cryptococcal meningitis; Cryptococcus neoformans; HIV; antiretroviral therapy; mortality (determinants); HIGH-DOSE FLUCONAZOLE; AMPHOTERICIN-B; ANTIRETROVIRAL THERAPY; INFECTION; ANTIGEN; FLUCYTOSINE; CLEARANCE; BURDEN; ADULTS; SERUM;

D O I：

10.1093/cid/cit794

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log(10) colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 x 10(9) cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.

引用

页码：736 / 745

页数：10

共 31 条

[1] Primary and opportunistic pathogens associated with meningitis in adults in Bangui, Central African Republic, in relation to human immunodeficiency virus serostatus [J].

Bekondi, Claudine ;

Bernede, Claire ;

Passone, Noella ;

Minssart, Pierre ;

Kamalo, Come ;

Mbolidi, Didier ;

Germani, Yves .

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2006, 10 (05) :387-395

[2] High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: A randomized trial [J].

Bicanic, Tihana ;

Wood, Robin ;

Meintjes, Graeme ;

Rebe, Kevin ;

Brouwer, Annemarie ;

Loyse, Angela ;

Bekker, Linda-Gail ;

Jaffar, Shabbar ;

Harrison, Thomas .

CLINICAL INFECTIOUS DISEASES, 2008, 47 (01) :123-130

[3] Fungal burden, early fungicidal activity, and outcome in cryptococcal meningitis in antiretroviral-naive or antiretroviral-experienced patients treated with amphotericin B or fluconazole [J].

Bicanic, Tihana ;

Meintjes, Graeme ;

Wood, Robin ;

Hayes, Madeleine ;

Rebe, Kevin ;

Bekker, Linda-Gail ;

Harrison, Thomas .

CLINICAL INFECTIOUS DISEASES, 2007, 45 (01) :76-80

[4] Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis: A Prospective Study [J].

Bicanic, Tihana ;

Meintjes, Graeme ;

Rebe, Kevin ;

Williams, Anthony ;

Loyse, Angela ;

Wood, Robin ;

Hayes, Madeleine ;

Jaffar, Shabbar ;

Harrison, Thomas .

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2009, 51 (02) :130-134

[5] Independent Association between Rate of Clearance of Infection and Clinical Outcome of HIV-Associated Cryptococcal Meningitis: Analysis of a Combined Cohort of 262 Patients [J].

Bicanic, Tihana ;

Muzoora, Conrad ;

Brouwer, Annemarie E. ;

Meintjes, Graeme ;

Longley, Nicky ;

Taseera, Kabanda ;

Rebe, Kevin ;

Loyse, Angela ;

Jarvis, Joseph ;

Bekker, Linda-Gail ;

Wood, Robin ;

Limmathurotsakul, Direk ;

Chierakul, Wirongrong ;

Stepniewska, Kasia ;

White, Nicholas J. ;

Jaffar, Shabbar ;

Harrison, Thomas S. .

CLINICAL INFECTIOUS DISEASES, 2009, 49 (05) :702-709

[6] Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial [J].

Brouwer, AE ;

Rajanuwong, A ;

Chierakul, W ;

Griffin, GE ;

Larsen, RA ;

White, NJ ;

Harrison, TS .

LANCET, 2004, 363 (9423) :1764-1767

[7]

Day JN, 2013, NEW ENGL J MED, V368, P2522, DOI [10.1056/NEJMoa1110404, 10.1056/NEJMc1305981]

[8] Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients [J].

Hakim, JG ;

Gangaidzo, IT ;

Heyderman, RS ;

Mielke, J ;

Mushangi, E ;

Taziwa, A ;

Robertson, VJ ;

Musvaire, P ;

Mason, PR .

AIDS, 2000, 14 (10) :1401-1407

[9] A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis [J].

Jackson, Arthur T. ;

Nussbaum, Jesse C. ;

Phulusa, Jacob ;

Namarika, Dan ;

Chikasema, Maria ;

Kanyemba, Creto ;

Jarvis, Joseph N. ;

Jaffar, Shabbar ;

Hosseinipour, Mina C. ;

van der Horst, Charles ;

Harrison, Thomas S. .

AIDS, 2012, 26 (11) :1363-1370

[10] The Phenotype of the Cryptococcus-Specific CD4+ Memory T-Cell Response Is Associated With Disease Severity and Outcome in HIV-Associated Cryptococcal Meningitis [J].

Jarvis, Joseph N. ;

Casazza, Joseph P. ;

Stone, Hunter H. ;

Meintjes, Graeme ;

Lawn, Stephen D. ;

Levitz, Stuart M. ;

Harrison, Thomas S. ;

Koup, Richard A. .

JOURNAL OF INFECTIOUS DISEASES, 2013, 207 (12) :1817-1828

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