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Hui Xu,1,* Shu-Ying Yu,2–4,* Meng-Lan Zhou,2–4 Ya-Ting Ning,2–4 Meng Xiao,2,4 Xiao-Gai Li,1 Meng Chen,2,5 Fanrong Kong,6 Sharon Chen,6 Liang Ming,1 Ying-Chun Xu2,3 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University and Key Laboratory of Clinical Laboratory of Henan Province, Henan 450003, People’s Republic of China; 2Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, People’s Republic of China; 5Department of Clinical Laboratory, Beijing Pinggu Hospital of Traditional Chinese Medicine, Beijing 101200, People’s Republic of China; 6Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR – New South Wales Health Pathology, The University of Sydney, Westmead Hospital, Westmead, NSW, Australia*These authors contributed equally to this workCorrespondence: Liang MingDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, 1E Jianshe Road, Zhengzhou, Henan 450052, People’s Republic of ChinaTel +86 371 6691 3118Email mingliang3072@163.com Ying-Chun XuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/Fax +86 10 6915 9766Email xycpumch@139.comIntroduction: As participants of the national China Hospital Invasive Fungal Surveillance Net program, we sought to describe the epidemiology and antifungal susceptibility patterns of yeast isolates obtained from patients with invasive fungal infection at the First Affiliated Hospital of Zhengzhou University, China.Methods: A total of 434 yeast isolates recovered from blood and other sterile body fluids were identified to species by matrix-assisted laser desorption ionization –time of flight mass spectrometry with or without supplementation by DNA sequencing. Antifungal susceptibilities were determined by Sensititre YeastOneTM YO10 methodology.Results: Candida albicans was the most common causative species (33.9% of isolates) but significantly decreased in frequency from 37.2% to 27.7% from 2012 to 2014. C. tropicalis was the next most common pathogen (25.1%), followed by C. parapsilosis complex (17.3%), C. glabrata (9%), and C. pelliculosa (6.7%), with other species comprising 8% of isolates. Caspofungin, micafungin, and anidulafungin exhibited potent in vitro activities against the majority of Candida isolates. Azoles demonstrated in vitro activities against C. albicans with a susceptibility rate of >95% and against C. parapsilosis complex, >95% isolates were susceptible. Among C. tropicalis and C. glabrata isolates, resistance rates to fluconazole and voriconazole were 11.9%, 9.1% and 7.7%, 28.2%, respectively. Of note, C. pelliculosa had a high incidence rate in newborns and high rates of resistance to fluconazole and voriconazole of 55.2% and 41.4%, respectively.Conclusion: The present study provided valuable local surveillance data on the epidemiology and antifungal susceptibilities of invasive yeast species, which is essential for guiding antifungal treatment protocol development.Keywords: invasive yeast infection, epidemiology, antifungal susceptibility

Li-Na Guo,1,2 Shu-Ying Yu,1– 3 Meng Xiao,1,2 Chun-Xia Yang,4 Chun-Mei Bao,5 Yan-Hua Yu,6 Li-Yan Ye,7 Yang Yang,1,2 Ge Zhang,1,2 Jie Liu,8 Guo-Wei Liang,9 Rong Min,10 Yu Zhu,11 Hong Lei,12 Yu-Lei Liu,13 Lin-Juan Liu,14 Yun-Jian Hu,15 Po-Ren Hsueh,16 Ying-Chun Xu1,2 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; 2Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447); 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences; 4Department of Infectious Diseases & Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University; 5Clinical Laboratory Medical Center, The Fifth Medical Center of Chinese PLA General Hospital; 6Department of Clinical Laboratory, You’an Hospital, Capital Medical University; 7Center for Clinical Laboratory Medicine, Chinese PLA General Hospital; 8Department of Clinical Laboratory, Seventh Medical Center, PLA General Hospital; 9Department of Clinical Laboratory, Aerospace Center Hospital; 10Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University; 11Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; 12Department of Clinical Laboratory, The 8th Medical Center of Chinese PLA General Hospital; 13Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University; 14Department of Clinical Laboratory, Peking University Cancer Hospital and Institute; 15Department of Clinical Laboratory, Beijing Hospital, Beijing, People’s Republic of China; 16Departments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanCorrespondence Ying-Chun XuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/ Fax +86 106 915 9766Email xycpumch@139.comPo-Ren HsuehDepartments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanTel +886-2-23224262 ext. 65355Fax +886-2-23955072Email hsporen@ntu.edu.twObjective: Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017.Materials and Methods: A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted.Results: Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012– 2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P< 0.05) compared with that observed in 2012– 2013, while micafungin resistance rates were < 5% for all tested Candida species.Conclusion: Our results suggest that species distribution has remained stable among IC-associated Candida isolates in Beijing. Resistance to micafungin was rare, but increased azole resistance among C. tropicalis isolates was noted. Our study provides information on local epidemiology that will be important for the selection of empirical antifungal agents and contributes to global assessments of antifungal resistance.Keywords: invasive fungal infections, Candida, species distribution, antifungal resistance, surveillance, Beijing

Shu-Ying Yu,1–3 Li Zhang,1,3 Sharon Chen,4 Fanrong Kong,4 Meng Xiao,1,3 He Wang,1,3 Xin Hou,1–3 Meng-Lan Zhou,1–3 Ge Zhang,1,3 Jing-Jia Zhang,1,3 Si-Meng Duan,1,3 Wei Kang,1,3 Ying-Chun Xu1,31Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, People’s Republic of China; 4Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR –New South Wales Health Pathology, The University of Sydney, Westmead, New South Wales, AustraliaIntroduction: We studied the species distribution and antifungal susceptibilities of Candida isolates causing refractory or recurrent oropharyngeal candidiasis (OPC) in a multicenter study in China (2013–2016).Methods: Species identification was performed using the Bruker Biotyper (Bruker Daltonics, Germany) matrix-assisted laser desorption/ionization time of flight mass spectrometry system supplemented by internal transcribed spacer sequencing as required. Antifungal susceptibilities were determined by the Clinical and Laboratory Standards Institute document (CLSI) M27-A3 broth microdilution methodology.Results: A total of 558 non-duplicate Candida isolates comprising 10 species were obtained from 535 patients. Candida albicans was the most common species (89.6%), followed by C. glabrata (5.2%), C. tropicalis (2.9%), and C. parapsilosis (0.7%). Azoles were active against C. albicans with susceptibility rates of 96% and 95.8% for fluconazole and voriconazole, respectively. MIC50 values of C. albicans to fluconazole, voriconazole, itraconazole, and miconazole were 1, 0.03, 0.25 and 0.12 μg/mL, respectively, higher than those in previous studies of which OPC patients (corresponding MIC50 values of 0.25 , 0.015 , 0.06 , and 0.03 μg/mL). Except for itraconazole, the MIC50 and MIC90 values of 58 non-C. albicans to other azoles were two to threefold higher than C. albicans. Miconazole, amphotericin B, nystatin, and 5-flucytosine had good in vitro antifungal activity for all isolates.Conclusion: The study provides valuable data on the species distribution and antifungal susceptibility of oropharyngeal Candida isolates from geographically diverse areas of China. C. albicans remains the most common species but with increasing rates of azoles resistance.Keywords: oral candidiasis, Candida, identification, antifungal susceptibility

One hundred and thirty-three clinical Trichosporon isolates were collected in the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program (2009 to 2016). Accurate identification was performed by sequencing of the intergenic spacer (IGS) 1 region. Among these isolates T. asahii (108, 81.2%) was the leading species, followed by T. dermatis (7, 5.3%), T. asteroides (5, 3.8%), T. inkin (5, 3.8%), T. dohaense (3, 2.3%), and one (0.7%) each of T. faecale, T. jirovecii, T. mucoides, T. coremiiforme and T. montevideense Both the VITEK MS (bioMérieux, Marcy l'Etoile, France) and Bruker Biotyper MS (Bruker Daltonics GmbH, Germany) platforms gave a high level (>97.5%) of correct identification when the species were present in the database. Geometric mean (GM) of amphotericin B MICs for T. asahii was 2-fold higher than for non-asahii Trichosporon High fluconazole MICs (≥8 μg/ml) were observed in 25% (27/108) of T. asahii and 16% (4/25) of non-asahii Trichosporon isolates. Itraconazole MICs were ≤0.5 μg/ml for 89.5% of the isolates. Voriconazole was the most potent antifungal agent in vitro, with GM of 0.09 μg/ml. Genotyping of the isolates using the IGS1 sequences alignment revealed that genotype1 was most common (41.7%), followed by genotype 4 (31.5%), 3 (23.1%), 5 (0.9%), 6 (0.9%) and 7 (1.8%). Our data of species distribution, genotypes and antifungal susceptibilities may contribute to a better understanding of the epidemiology of invasive Trichosporon infections throughout China.

Shu-Ying Yu,1–3 Li-Na Guo,1,3 Meng Xiao,1,3 Timothy Kudinha,4,5 Fanrong Kong,4 He Wang,1,3 Jing-Wei Cheng,1–3 Meng-Lan Zhou,1–3 Hui Xu,6 Ying-Chun Xu1–3 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China; 4Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR – Pathology West, University of Sydney, Westmead Hospital, Westmead, NSW, Australia; 5Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Westmead, NSW, Australia; 6Department of Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Background: Trichosporon dohaense is a rare fungal species that has not been described in human invasive infections. Patients and methods: In this study, we investigated two T. dohaense isolates from patients with invasive infections in two hospitals in China, as part of the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program. Both patients were under immunocompromised conditions. Results: On chromogenic agar, T. dohaense isolates were dark blue, similar to the color of Candida. tropicalis, but the characteristic moist colony appearance was quite different from that of T.asahii. The two isolates were misidentified as T. asahii and T. inkin by the VITEK 2 YST system. The rDNA internal transcribed spacer (ITS) region and the D1/D2 domain sequences of the two T.dohaense isolates were 100% identical to T. dohaense type strain CBS10761T. The sequence of the intergenic spacer region-1 also clearly distinguished the species. Of the three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry systems, Bruker Biotyper and Autobio MS correctly identified the two isolates to species level, whereas Vitek MS systems misidentified them as T. ovoides or T. asteroides. Echinocandins exhibited no in vitro activities against the two T. dohaense isolates. In addition, the isolates exhibited intermediate susceptibility to fluconazole (with minimal inhibitory concentrations [MICs] of 8 and 16 µg/mL) and itraconazole, voriconazole, and posaconazole (MICs of 0.25–1 µg/mL). T. dohaense demonstrated susceptibility to amphotericin B with MIC of 1 µg/mL. The MICs of fluconazole and voriconazole in our study were higher than the MIC50 of 62 for T. asahii isolates (4 and 0.064 µg/mL) in the CHIF-NET program. Conclusion: This case study points to a possible emergence of T. dohaense as an opportunistic human invasive fungal pathogen, and the reduced susceptibility should be noted. Keywords: Trichosporon dohaense, invasive infection, emerging pathogen, identification, reduced susceptibility