Genotypes and Antifungal Susceptibility of Cryptococcus neoformans Species Complex Causing Invasive Diseases in China: Predominance of C. neoformans var. Grubii Sequence Type 5, and Emergence of Isolates Non-Susceptible to Fluc

M. Xiao1, X. Fan1, S. Chen2, F. Kong2, H. Wang1, Y-C. Xu1

Author address: 

1Peking Union Med. Coll. Hosp., Beijing, China, 2Westmead Hosp., Westmead, Australia


Background: There are limited data on cryptococcosis in China. Here we investigated the nationwide genetic structure and antifungal susceptibility of the Cryptococcus neoformans species complex over a five-year period.Methods: A total of 312 C. neoformans species complex isolates from patients with cryptococcosis collected from 10 hospitals from August 2009 to July 2014 in China were studied. The isolates were identified by sequencing of the rDNA internal transcribed spacer (ITS) region, and multilocus sequence typing was used for genotyping of the species complex. The ability of two MALDI-TOF MS systems to identify C. neoformans complex isolates were also evaluated. In vitro susceptibility to six antifungal drugs was determined by the Sensititre YeastOne method.Results: Of 312 isolates, 211 (67.6%) were isolated from cerebrospinal fluid (CSF), followed by blood cultures (n = 74, 23.7%). C. neoformans was the most common species (n = 305, 97.8%), of which C. neoformans var. grubii sequence type (ST) 5 were predominant (n = 272, 89.2%), followed by ST31 (n = 31, 6.1%), while other C. neoformans var. grubii STs (n = 12 in all, 3.9%) and C. neoformans var. neoformans (n = 2, 0.7%) were rare. Molecular serotyping found all C. neoformans var. grubii were serotype A, and the two C. neoformans var. neoformans isolates were serotype AD heterozygote. C. gattii were also less common (n = 7, 2.2%). Two MALDI-TOF MS showed good capacity in identifying C. neoformans var. grubii and var. neoformans isolates (>99%) but less satisfying in identifying C. gattii (Bruker Biotyper 71.4%, Vitek MS, 0%). Amongst C. neoformans var. grubii isolates, the proportion of fluconazole non-wild-type isolates were significantly higher in the fourth year (23.9%) comparing to previous three years (0-2.1%), including five fluconazole highly non-susceptible isolates (minimum inhibitory concentrations ≥ 32 mg/L) that all belonged to C. neoformans ST5.Conclusions: In summary, C. neoformans var. grubii ST5 was the most predominant in China. The emergence of fluconazole highly nonsusceptible isolates and their geographic difference warrant continuous surveillance.

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Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)