Abstract
BackgroundThe 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.MethodsA 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.ResultsA 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.ConclusionsAdherence 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.
Highlights
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
In the 2010 Infectious Diseases Society of America (IDSA) guidelines, higher dose fluconazole alone or in combination with other antifungals was recommended for both consolidation and salvage therapy in Human immunodeficiency virus (HIV)-uninfected cryptococcal meningitis (CM) patients, compared with 400 mg/day in the 2000 version of these guidelines [19, 20]
We conducted a retrospective study among HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy, and evaluated the efficacy and safety of high dose fluconazole regimens
Summary
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. Fluconazole is a triazole with excellent in vitro and in vivo activity against Cryptococcus It has been widely used in CM as consolidation and maintenance therapy, Zhao et al BMC Infectious Diseases (2018) 18:643 usually at a dosage equal to or lower than 400 mg/day. In the 2010 Infectious Diseases Society of America (IDSA) guidelines, higher dose fluconazole alone or in combination with other antifungals was recommended for both consolidation and salvage therapy in HIV-uninfected CM patients, compared with 400 mg/day in the 2000 version of these guidelines [19, 20]. Evidence of high dose fluconazole for treatment of CM was mainly based on studies of HIV-infected populations, and remained sparse in HIV-uninfected patients. We conducted a retrospective study among HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy, and evaluated the efficacy and safety of high dose fluconazole regimens
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