Antifungal susceptibility profile and local epidemiological cut-off values of
Yarrowia
(
Candida
)
lipolytica
: an emergent and rare opportunistic yeast
Authors: Yu Jinhan , Liu Xueqing , Guo Dawen , Yang Wenhang , Chen Xinfei , Zou Guiling , Wang Tong , Pang Shichao , Zhang Ge , Dong Jingjing , Xu Yingchun , Zhao Ying ,   on behalf of the National China Hospital Invasive Fungal Surveillance Network (CHIF-NET)
Published: December 2023

ABSTRACT

The antifungal susceptibility profile and epidemiological cut-off values (ECOFFs) of
Yarrowia lipolytica
, a rare opportunistic yeast, remain unclear. We conducted a comprehensive multi-method study on clinical isolates from various central hospitals, based on the China Hospital Invasive Fungal Surveillance Network (2009–2022). Our objective was to evaluate the antifungal susceptibility of
Y. lipolytica
, establish its local ECOFFs (L-ECOFFs), and compare the performance of the ATB FUNGUS 3 (ATB), Sensititre YeastOne (SYO), and minimum inhibitory concentration (MIC) test strip (MTS) with that of the broth microdilution (BMD) method. L-ECOFFs were established using ECOFFinder, and we examined
ERG11
mutations to assess the reliability of the L-ECOFFs. The L-ECOFF for fluconazole was 8 µg/mL. Non-wild-type isolates of antifungal drugs, such as flucytosine and azoles, were exclusively isolated from patients. Additionally, we detected that four strains with the
ERG11
A395T mutation (azole MIC >L-ECOFF) may be associated with the exposure to azole drugs. For azoles, ATB showed the highest essential agreement with the BMD (98.18%–100%), followed by SYO (85.45%–100%). However, ATB could not detect susceptibility to echinocandins, while SYO exhibited the highest agreement (98.18%–100%) in detecting echinocandin susceptibility. Our findings indicate that acquired azole cross-resistance has emerged despite
Y. lipolytica
infections being rare. This research provides crucial antifungal susceptibility data and establishes the initial L-ECOFFs for
Y. lipolytica
. The SYO is recommended as the optimal laboratory antifungal susceptibility testing method for
Y. lipolytica
, followed by ATB, whereas the use of MTS requires caution. We hope that this study will facilitate improved clinical management of
Y. lipolytica
infections.

IMPORTANCE

Yarrowia lipolytica
, also known as
Candida lipolytica
, is an emerging opportunistic “rare pathogenic yeast”. Due to the limited data on its antifungal susceptibility, the clinical treatments become challenging. Based on the China Hospital Invasive Fungal Surveillance Network (2009–2022), we conducted a comprehensive multi-method study on clinical isolates from various central hospitals. This study is currently the largest study carried out to assess the antifungal susceptibility of
Y. lipolytica
. It is also the first to establish local epidemiological cut-off values (L-ECOFFs), identify its
ERG11
mutations, and assess the consistency between the three prevalent commercial antifungal susceptibility testing methods and the broth microdilution method. We recommend the Sensititre YeastOne as the best option for antifungal susceptibility testing for
Y. lipolytica
, followed by the ATB FUNGUS 3. Nevertheless, practitioners should use the MIC test strip with discretion.