Antifungal susceptibility profile and local epidemiological cut-off values of Yarrowia ( Candida ) lipolytica : an emergent and rare opportunistic yeast

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.

Stephanoascus ciferrii Complex: The Current State of Infections and Drug Resistance in Humans

“…After genome sequencing, they described the A395T mutation in the ERG11 gene, previously described in fluconazole-resistant Candida strains, which can explain the high MIC found in this clinical isolate. In line with the publication of Lavergne et al [92], Yu et al [93] reported four additional azole-resistant Y. lipolytica clinical strains presenting the A395T mutation in the ERG11 gene. Despite the rarity of Y. lipolytica infections, it is important to emphasize that there has been an emergence of acquired azole cross-resistance.…”

“…Stavrou et al [91] demonstrated that among twenty-seven Y. lipolytica isolates, 74.1% were resistant to echinocandins. In contrast, Yu et al [93] have not reported resistance strains of Y. lipolytica in their retrospective study, and the use of echinocandins in bloodstream infections due to Y. lipolytica had a favourable outcome [98]. Based on the literature, no data regarding the resistance mechanism for echinocandins are described for the S. ciferrii complex as well as for Y. lipolytica, but elevated echinocandin MICs have been associated with several single amino acid substitutions caused by mutations in specific "hot spot" regions of the well-conserved target genes FKS1 of Y. lipolytica [99].…”