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The association between fluconazole dose and MIC with mortality and persistence in candidemia

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Abstract

To evaluate the association between fluconazole exposure parameters and clinical outcomes in patients with candidemia. We retrospectively included all adults with candidemia in a single center from January 2009 to December 2017, treated initially with fluconazole for fluconazole-susceptible candidemia. We assessed the association between fluconazole exposure parameters and 30-day mortality or 14-day clinical failure, a composite of mortality at day 14 or persistent candidemia ≥ 72 h, in all patients and in patients with C. glabrata candidemia. During the study period, 158 patients fulfilled the inclusion criteria. Main species were C. albicans 66 (41.8%), C. glabrata 35 (22.2%), and C. parapsilosis 31 (19.6%). Sixty patients (38%) died within 30 days. Sixty-one patients (38.6%) experienced 14-day failure. In 30-day survivors, the median AUC24/MIC was 2279 [398, 5989] versus 1764 [238, 6714] h in non-survivors, p = 0.75. Median fluconazole MIC was 0.75 [0.25, 4] and 1 [0.22, 5.50] mg/L, p = 0.54, respectively. Similar non-significant differences were found for other fluconazole exposure parameters and in the 14-day clinical failure analysis. For C. glabrata, a higher AUC24/MIC was observed among 30-day survivors with a median of 230 [77, 539] compared to 96 [75, 164] h in non-survivors, p = 0.008, in parallel with a trend for lower MIC values (median 7 [1, 2] versus 16 [8, 24] mg/L, p = 0.06, respectively). Currently used fluconazole dosing has no association with clinical outcome in Candida with low MIC values. For Candida species with high MICs, attention to dosing is needed.

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Acknowledgments

The study was presented in the 29th European Congress of Clinical Microbiology and Infectious Diseases that was held in Amsterdam, Netherlands, April 2019.

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Authors and Affiliations

  1. Infectious Diseases Institute, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel

    Nesrin Ghanem-Zoubi & Mical Paul

  2. Internal Medicine Department D, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel

    Majd Qasum

  3. Internal Medicine Department B, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel

    Johad Khoury

  4. The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Efron 1 St, 3525433, Haifa, Israel

    Danny Zorbavel & Merav Arnon

  5. Microbiology Laboratory, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel

    Yuval Geffen

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  1. Nesrin Ghanem-Zoubi
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Correspondence to Nesrin Ghanem-Zoubi.

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Ghanem-Zoubi, N., Qasum, M., Khoury, J. et al. The association between fluconazole dose and MIC with mortality and persistence in candidemia. Eur J Clin Microbiol Infect Dis 38, 1773–1780 (2019). https://doi.org/10.1007/s10096-019-03611-1

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