This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec 28;2(4):ofv157.
doi: 10.1093/ofid/ofv157. eCollection 2015 Dec.

Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

Affiliations

Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

Melissa A Rolfes et al. Open Forum Infect Dis. .

Abstract

Background. Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%-50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods. Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7-1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by "enhanced consolidation" therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1-2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results. Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6-2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions. Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.

Keywords: HIV; amphotericin; clinical outcome; cryptococcal meningitis.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Cerebrospinal fluid (CSF) culture positivity and vital status outcomes for individuals with human immunodeficiency virus-associated cryptococcal meningitis in the Cryptococcal Optimal Antiretroviral Therapy Timing (COAT) trial.
Figure 2.
Figure 2.
Kaplan-Meier survival probabilities starting at the end of 2 weeks of induction amphotericin therapy (week 0) through 6 months (26 weeks), by cerebrospinal fluid (CSF) culture positivity at the end of amphotericin therapy for individuals with human immunodeficiency virus-associated cryptococcal meningitis in the Cryptococcal Optimal Antiretroviral Therapy Timing trial.
Figure 3.
Figure 3.
Kaplan-Meier survival probabilities by cerebrospinal fluid (CSF) culture positivity, at the end of amphotericin therapy, for the following: (A) 6-month mortality in the early antiretroviral therapy (ART) treatment arm (initiating ART 7–11 days after cryptococcal diagnosis), and (B) 6-month mortality in the deferred ART treatment arm (initiating ART 5 weeks after cryptococcal diagnosis) for individuals with human immunodeficiency virus-associated cryptococcal meningitis in the Cryptococcal Optimal Antiretroviral Therapy Timing trial.

References

    1. Corbett EL, Churchyard GJ, Charalambos S et al. . Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis 2002; 34:1251–8. - PubMed
    1. Durski KN, Kuntz KM, Yasukawa K et al. . Cost-effective diagnostic checklists for meningitis in resource-limited settings. J Acquir Immune Defic Syndr 2013; 63:e101–8. - PMC - PubMed
    1. Lawn SD, Harries AD, Anglaret X et al. . Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 2008; 22:1897–908. - PMC - PubMed
    1. Okongo M, Morgan D, Mayanja B et al. . Causes of death in a rural, population-based human immunodeficiency virus type 1 (HIV-1) natural history cohort in Uganda. Int J Epidemiol 1998; 27:698–702. - PubMed
    1. Brouwer AE, Rajanuwong A, Chierakul W et al. . Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomized trial. Lancet 2004; 363:1764–7. - PubMed

LinkOut - more resources

Full text links
Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /