Development of fluconazole resistance in a series of Candida parapsilosis isolates from a persistent candidemia patient with prolonged antifungal therapy.
BACKGROUND
Candida parapsilosis was the most common species causing candidemia in the 2010 China Hospital Invasive Fungal Surveillance Net (CHIF-NET) database. Compared to Candida albicans, the description of azole resistance and mechanisms in C. parapsilosis is very limited. We report a patient with C. parapsilosis candidemia over several months, due to a probable intravascular source, who developed fluconazole resistance after prolonged treatment.


METHODS
An 82 year-old male had a hospital admission of approximately 1.5 years duration. He was initially admitted with acute pancreatitis. Prior to succumbing to the illness, he developed candidemia and treated with three antifungal drugs for nearly 5 months, at suboptimal doses and without source control. Following treatment, 6 blood cultures were still positive for C. parapsilosis. The last 2 strains were resistant to fluconazole (MICs 32 μg/mL) and intermediate to voriconazole (MICs 0.5 μg/mL). Microsatellite multilocus analysis indicated that the 6 isolates from the patient belonged to a single genotype. The first 4 isolates were susceptible to fluconazole (MICs 2 μg/mL) and voriconazole (MICs 0.015-0.03 μg/mL), which were slightly higher than susceptible control strains from other patients. Overexpression of MDR1 genes were detected in the two resistant isolates, and this was associated with a homozygous mutation in MRR1 genes (T2957C /T2957C), with the amino acid exchange L986P.


CONCLUSIONS
This case corroborates that the resistant C. parapsilosis isolates can emerge in the setting of complicated infections and the extensive use of antifungal agents, emphasizing the need for standardizing and improving the antifungal treatment as well as source control in the treatment of infection diseases.
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. zhangli19870711@163.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China. zhangli19870711@163.com.
Li
L
Zhang
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. cjtcxiaomeng@aliyun.com.
Meng
M
Xiao
Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, University of Sydney, Westmead Hospital, Darcy Road, Westmead, Sydney, NSW, 2145, Australia. watts.idmicro@gmail.com.
Matthew R
MR
Watts
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. raulshiny@163.com.
He
H
Wang
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. fanxin12356@163.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China. fanxin12356@163.com.
Xin
X
Fan
Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, University of Sydney, Westmead Hospital, Darcy Road, Westmead, Sydney, NSW, 2145, Australia. kongfr_nk@yahoo.com.au.
Fanrong
F
Kong
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. xycpumch@139.com.
Ying-Chun
YC
Xu
D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D058387:Candidemia / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D002681:China; D025141:Drug Resistance, Fungal / Q000235:genetics; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D015725:Fluconazole