The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole

Shang-Yi Lin; Ho-Yin Huang; Lin-Li Chang; Ya-Ling Wang; Tun-Chieh Chen; Ko Chang; Hung-Pin Tu; Po-Liang Lu

doi:10.1016/j.cmi.2024.03.023

The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole

Clin Microbiol Infect. 2024 Mar 23:S1198-743X(24)00154-X. doi: 10.1016/j.cmi.2024.03.023. Online ahead of print.

Authors

Shang-Yi Lin¹, Ho-Yin Huang², Lin-Li Chang³, Ya-Ling Wang², Tun-Chieh Chen⁴, Ko Chang⁵, Hung-Pin Tu⁶, Po-Liang Lu⁷

Affiliations

¹ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
² Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Microbiology and Immunology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁴ Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁶ Department of Public Health and Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: d830166@gmail.com.

PMID: 38527614
DOI: 10.1016/j.cmi.2024.03.023

Abstract

Objectives: The trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the MIC. We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole (FLC) therapy.

Methods: We retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with FLC for FLC-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories: residual (0.1-5%), slight (6-10%), moderate (11-15%), and heavy trailers (>15%).

Results: Among isolates from 190 patients, the proportions of heavy trailers at 24 hours, 48 hours, and 72 hours were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 hours was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p = 0.007). A multivariate analysis showed that immunosuppression (OR = 7.92; 95% CI: 2.38-26.39, p = 0.001), hospitalization days after the index date of C. albicans identification (OR = 1.03; 95% CI: 1.01-1.05, p = 0.011), and heavy trailing isolates at 48 hours (OR = 10.04; 95% CI: 1.27-79.88, p = 0.029) were independent factors for persistent candidemia.

Discussion: The current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment.

Keywords: Candida albicans; Fluconazole; Persistent candidemia; Tolerance; Trailing.