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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Clinical Microbiology
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1455145

Antifungal Susceptibility, Molecular Epidemiology, and Clinical Risk Factors of Candida glabrata in Intensive Care Unit in a Chinese Tertiary Hospital

Provisionally accepted
Si-Jia Huang Si-Jia Huang 1,2Geng Lv Geng Lv 1,2Yi-Hui Song Yi-Hui Song 3Jun-Tao Zhao Jun-Tao Zhao 1Jin-Yan Liu Jin-Yan Liu 2Lu-Ling Wang Lu-Ling Wang 1,2Ming-Jie Xiang Ming-Jie Xiang 1,2*
  • 1 Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2 Department of Laboratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 3 Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    The increasing incidence and high mortality rate of Candida glabrata infection in ICU patients is an important issue. Therefore, it is imperative to investigate the antifungal susceptibility profiles and epidemiological characteristics in local regions.Methods: Herein, antifungal susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs) of eight antifungal drugs. Multilocus sequence typing (MLST) was used to study the strain genotype, geographical distribution, and susceptibility to antifungal agents among C. glabrata isolates. The mechanism of echinocandin resistance was explored by sequencing the FKS1 and FKS2 genes (encoding 1,3-β-D-glucan synthases) of echinocandin-resistant C. glabrata strains. Moreover, we further investigated the clinical manifestations and the various risk factors of patients infected with C. glabrata in the ICU.We selected 234 C. glabrata isolates from 234 patients in the ICU randomly for the followup study. Cross-resistance was found among the ICU C. glabrata isolates. Analysis using MLST showed that the genetic diversity among the C. glabrata isolates was low. Furthermore, sequence type showed no correlation with the antifungal resistance profiles, but was associated with geographical distribution. We also revealed novel mutations in FKS1 (S629P) and FKS2 (W1497stop) that mediated high-level echinocandin resistance (MIC >8 µg/mL). More than 14 days' stay in ICU (P=0.007), Acute Physiology and Chronic Health Evaluation II (APACHE-Ⅱ) score (P=0.024), prior antifungal exposure (P=0.039) and lung disease (P=0.036) were significantly associated with antifungal resistant/non-wildtype C. glabrata infection.Our study shed light on the antifungal susceptibility, molecular epidemiology, and clinical risk factors of C. glabrata in the ICU of a Chinese Tertiary Hospital. Importantly, we revealed the molecular mechanism of echinocandin resistance. These results highlight the significance of continued surveillance in ICUs and provide data support for the treatment of C. glabrata in clinics.

    Keywords: Candida glabrata, Intensive care unit (ICU), antifungal susceptibility, Multilocus sequence typing (MLST), Echinocandin resistance, Risk factors

    Received: 26 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Huang, Lv, Song, Zhao, Liu, Wang and Xiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ming-Jie Xiang, Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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