title: Predominance of Cryptococcus neoformans var. grubii multilocus sequence type 5 and emergence of isolates with non-wild-type minimum inhibitory concentrations to fluconazole: a multi-centre study in China.
abstract: There are few data on the molecular epidemiology of cryptococcosis in China. Here we investigated the species distribution, molecular types and antifungal susceptibilities of 312 Cryptococcus neoformans species complex isolates from ten hospitals over 5 years. Isolates were identified by internal transcribed spacer (ITS) sequencing and by two matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems. Multilocus sequence typing (MLST) was used to verify species/variety and to designate molecular types. Susceptibility to six antifungal drugs was determined by the Sensititre YeastOne™ method. Cryptococcus neoformans was the predominant species (305/312 isolates (97.8%), all were ITS type 1, serotype A), of which 89.2% (272/305) were C. neoformans var. grubii MLST sequence type (ST) 5 and 6.2% (19/305) were ST31. Other C. neoformans var. grubii STs were rare but included six novel STs. Only two strains were C. neoformans var. neoformans (both serotype AD). Cryptococcus gattii was uncommon (n = 7, four ITS types) and comprised five MLST STs including one novel ST. For C. neoformans var. grubii, the proportion of isolates with non-wild-type MICs to fluconazole significantly rose in the fourth study year (from 0% (0/56 isolates) in the first year to 23.9% (17/71) in the fourth year), including five isolates with fluconazole MICs of ≥32 mg/L. The study has provided useful data on the species epidemiology and their genetic diversity and antifungal susceptibility. The proportional increase in isolates with non-wild-type MICs to fluconazole is noted.
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: H-T
authors.initials: HT
authors.lastname: Dou
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Xiao
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: M
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Z-D
authors.initials: ZD
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: S-L
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: K
authors.initials: K
authors.lastname: Liao
authors.affiliation: Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Chu
authors.affiliation: Department of Clinical Laboratory, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China.
authors.forename: T-S
authors.initials: TS
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: G-L
authors.initials: GL
authors.lastname: Zou
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, and Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: xycpumch@139.com.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Xu
authors.affiliation: Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: zhengyinl@hotmail.com.
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Liu
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D002681:China / Q000453:epidemiology; D003455:Cryptococcus neoformans / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D004271:DNA, Fungal / Q000032:analysis; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing / Q000379:methods*; D016533:Mycological Typing Techniques / Q000379:methods*; D010802:Phylogeny; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal; D015725:Fluconazole
keywords: Antifungal susceptibility; China; Cryptococcus; Invasive fungal infections; Molecular epidemiology; Species distribution