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High dose fluconazole in salvage therapy for HIV-uninfected cryptococcal meningitis.

Zhao, H-Z; Wang, R-Y; Wang, X; Jiang, Y-K; Zhou, L-H; Cheng, J-H; Huang, L-P; Harrison, TS; Zhu, L-P (2018) High dose fluconazole in salvage therapy for HIV-uninfected cryptococcal meningitis. BMC Infect Dis, 18 (1). p. 643. ISSN 1471-2334 https://doi.org/10.1186/s12879-018-3460-7
SGUL Authors: Harrison, Thomas Stephen

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Abstract

BACKGROUND: The 2010 Infectious Diseases Society of America (IDSA) guidelines for management of cryptococcal diseases recommend high dose fluconazole (≥ 800 mg/day), either alone or with other antifungal drugs, as alternative anticryptococcal choices. But evidence for its use in the treatment of HIV-uninfected cryptococcal meningitis (CM) remains sparse. METHODS: A retrospective analysis of HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy from January 2011 to December 2016 at Huashan Hospital, Shanghai, China was performed. Efficacy and safety were assessed, and mortality and prognostic factors evaluated. RESULTS: A total of 44 patients were studied including 19 refractory to amphotericin B induction therapy, 8 refractory to fluconazole consolidation therapy (400 mg/d), and 17 intolerant of antifungal drugs. For salvage, 11 patients received triple therapy of high dose fluconazole, amphotericin B and flucytosine, 20 received dual therapy of high dose fluconazole and flucytosine, 13 received monotherapy of high dose fluconazole. Median duration of high dose fluconazole in salvage regimens was 136.5 days (range, 1-667 days). Clinical response rates were 72.1% (31/43) and 83.7% (36/43) when assessed at 2 weeks and the end of salvage therapy, respectively. Adverse events possibly related to high dose fluconazole occurred in 54.5% (24/44) of the patients, and all were mild or moderate. From the initiation of salvage therapy, 1-year all-cause mortality was 13.6% (6 of 44 patients) among the study population with no significant difference in refractory or intolerant patients. CONCLUSIONS: Adherence to guideline recommendations of high dose fluconazole, alone or in combination with other antifungals, was safe and often effective for salvage therapy of HIV-uninfected CM patients.

Item Type: Article
Additional Information: © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Cryptococcal meningitis, Efficacy, HIV-uninfected, High dose fluconazole, Safety, 0605 Microbiology, 1103 Clinical Sciences, 1108 Medical Microbiology, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: BMC Infect Dis
ISSN: 1471-2334
Language: eng
Dates:
DateEvent
12 December 2018Published
31 October 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 30541454
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110483
Publisher's version: https://doi.org/10.1186/s12879-018-3460-7

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