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

  • Nesrin Ghanem-ZoubiEmail author
  • Majd Qasum
  • Johad Khoury
  • Danny Zorbavel
  • Merav Arnon
  • Yuval Geffen
  • Mical Paul
Original Article
  • 39 Downloads

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.

Keywords

Candidemia Fluconazole Mortality Area under curve Minimal inhibitory concentration 

Notes

Acknowledgments

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study was approved by the ethics committee at Rambam Hospital.

Informed consent

Not required; not applicable.

Supplementary material

10096_2019_3611_MOESM1_ESM.docx (21 kb)
ESM 1 (DOCX 20 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Nesrin Ghanem-Zoubi
    • 1
    Email author
  • Majd Qasum
    • 2
  • Johad Khoury
    • 3
  • Danny Zorbavel
    • 4
  • Merav Arnon
    • 4
  • Yuval Geffen
    • 5
  • Mical Paul
    • 1
  1. 1.Infectious Diseases InstituteRambam Health Care CampusHaifaIsrael
  2. 2.Internal Medicine Department DRambam Health Care CampusHaifaIsrael
  3. 3.Internal Medicine Department BRambam Health Care CampusHaifaIsrael
  4. 4.The Ruth and Bruce Rappaport Faculty of Medicine, TechnionIsrael Institute of TechnologyHaifaIsrael
  5. 5.Microbiology LaboratoryRambam Health Care CampusHaifaIsrael

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