title: Changes in karyotype and azole susceptibility of sequential bloodstream isolates from patients with Candida glabrata candidemia.
abstract: We examined the changes in genotypes and azole susceptibilities among sequential bloodstream isolates of Candida glabrata during the course of fungemia and the relationship of these changes to antifungal therapy. Forty-one isolates were obtained from 15 patients (9 patients who received antifungal therapy and 6 patients who did not) over periods of up to 36 days. The isolates were analyzed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and tested for antifungal susceptibility to fluconazole, itraconazole, and voriconazole. PFGE typing consisted of electrophoretic karyotyping and restriction endonuclease analysis of genomic DNA by use of NotI (REAG-N). The 41 isolates yielded 23 different karyotypes and 11 different REAG-N patterns but only 3 MLST types. The sequential strains from each patient had identical or similar REAG-N patterns. However, they had two or three different karyotypes in 6 (40%) of 15 patients. The isolates from these six patients exhibited the same or similar azole susceptibilities, and five patients did not receive antifungal therapy. Development of acquired azole resistance in sequential isolates was detected for only one patient. For this patient, an isolate of the same genotype obtained after azole therapy showed three- or fourfold increases in the MICs of all three azole antifungals and exhibited increased expression of the CgCDR1 efflux pump. This study shows that karyotypic changes can develop rapidly among sequential bloodstream strains of C. glabrata from the same patient without antifungal therapy. In addition, we confirmed that C. glabrata could acquire azole resistance during the course of fungemia in association with azole therapy.
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School, 8 Hakdong Dongku, Gwangju 501-757, South Korea. shinjh@chonnam.ac.kr
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Shin
authors.forename: Myung Jong
authors.initials: MJ
authors.lastname: Chae
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Song
authors.forename: Sook-In
authors.initials: SI
authors.lastname: Jung
authors.forename: Duck
authors.initials: D
authors.lastname: Cho
authors.forename: Seung Jung
authors.initials: SJ
authors.lastname: Kee
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Myung Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Soon Pal
authors.initials: SP
authors.lastname: Suh
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Ryang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology*; D002675:Child, Preschool; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D016469:Fungemia / Q000188:drug therapy / Q000382:microbiology*; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D008137:Longitudinal Studies; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016533:Mycological Typing Techniques; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D001393:Azoles; D004271:DNA, Fungal