LETTER
Candida is the predominant cause of fungemia worldwide (1), including critical-care settings (2). Approximately 60% of all fungemia is caused by Candida albicans, followed by C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and the emerging pathogen C. dubliniensis (3). C. dubliniensis was originally recovered from the oral cavity of an AIDS patient in Dublin, Ireland, in 1995 (4) and is reported to cause candidemia with a frequency estimated to be 0.2 to 3% (3). Although recent improvements in laboratory methods for Candida identification have been noted (5), the prevalence of C. dubliniensis may still be underestimated (6) because of the phenotypic and genotypic similarity to C. albicans and the difficulty of differentiating these two Candida species. This study evaluated the ability of the FilmArray Blood Culture Identification (BCID) panel (BioFire Diagnostics, Salt Lake City, UT) to discriminate C. albicans and C. dubliniensis from positive blood culture. The FilmArray BCID panel is a nested multiplexed PCR test that identifies pathogens directly in positive blood cultures, including C. albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis. C. dubliniensis is not included in the panel.
Twenty-seven contrived blood cultures were evaluated with the BCID panel to examine the cross-reactivity of the panel with C. dubliniensis. The reference isolates used in this study included 20 C. dubliniensis and 7 C. albicans isolates (Table 1) whose identities were previously confirmed to the species level by both phenotypic (i.e., germ tube test; chlamydoconidium formation, and appearance) and genotypic (i.e., comparison of the complete internal transcribed spacer 1 and 2 region sequences of the ribosomal DNA complex) analyses (4, 7–9). BD Bactec Plus Aerobic/F culture bottles (BD Diagnostic Systems, Malvern, PA) containing whole blood were each inoculated with a reference isolate. Contrived cultures were incubated in a Bactec 9240 cabinet until positive and then tested with the BCID panel according to the manufacturer's instructions (10).
TABLE 1.
Analysis of contrived blood cultures containing C. albicans or C. dubliniensis with the FilmArray BCID panel
| Speciesa and strain | BCID panel result |
|---|---|
| C. albicans | |
| B7560-08 | C. albicans |
| B7706-08 | C. albicans |
| B8627-09 | C. albicans |
| B9005-09 | C. albicans |
| B9010-09 | C. albicans |
| B9028-09 | C. albicans |
| ATCC 10231 | C. albicans |
| C. dubliniensis | |
| CU001 | NDb |
| CU002 | ND |
| CU003 | ND |
| CU004 | ND |
| CU005 | ND |
| CU006 | ND |
| CU007 | ND |
| CU008 | ND |
| CU009 | ND |
| CU010 | ND |
| CU011 | ND |
| 20-070-29 | ND |
| 20-070-30 | ND |
| 20-070-31 | ND |
| 20-070-32 | ND |
| NE TNMC,120905 | ND |
| NE TNMC,121007 | ND |
| NE TNMC,072407 | ND |
| NE TNMC,012608 | ND |
| NE TNMC,041108 | ND |
Species identities were verified by both phenotypic and genetic analyses.
ND, not detected.
The BCID panel correctly detected C. albicans (7/7) but did not detect C. dubliniensis (0/20) in contrived blood cultures, indicating that the BCID panel can discriminate these two genetically and phenotypically similar species. These results indicated that blood cultures positive for C. albicans by the BCID panel could be reported with confidence as C. albicans. Furthermore, on the basis of BCID analyte specificity for C. albicans, germ tube-positive and BCID panel-negative yeast isolates can be presumptively identified as C. dubliniensis with confirmatory identification to follow.
Direct testing of positive blood cultures by nucleic acid amplification tests (NAATs) provides rapid identification of pathogens and facilitates appropriate antimicrobial therapy. Although NAATs can lack discriminatory power for highly related organisms, this study showed that the FilmArray BCID panel is capable of distinguishing C. albicans from the genetically related and phenotypically similar species C. dubliniensis in positive blood cultures. Future studies will likely support C. dubliniensis as an important cause of human disease and that the addition of this analyte to the BCID panel could help optimize the clinical management of patients with candidemia and improve the epidemiology of candidemia as it relates to C. albicans and C. dubliniensis.
REFERENCES
- 1.Delaloye J, Calandra T. 2014. Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence 5:161–169. doi: 10.4161/viru.26187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kollef M, Micek S, Hampton N, Doherty J, Kumar A. 2012. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 54:1739–1746. doi: 10.1093/cid/cis305. [DOI] [PubMed] [Google Scholar]
- 3.Falagas M, Roussos N, Vardakas K. 2010. Relative frequency of C. albicans and the various non-albicans Candida spp among candidemia isolates from inpatients in various parts of the world: a systematic review. Int J Infect Dis 14:e954–e966. doi: 10.1016/j.ijid.2010.04.006. [DOI] [PubMed] [Google Scholar]
- 4.Sullivan D, Westerneng T, Haynes K, Bennett D, Coleman D. 1995. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology 141:1507–1521. doi: 10.1099/13500872-141-7-1507. [DOI] [PubMed] [Google Scholar]
- 5.Pfaller M, Woosley L, Messer S, Jones R, Castanheira M. 2012. Significance of molecular identification and antifungal susceptibility of clinically significant yeasts and moulds in a global antifungal surveillance programme. Mycopathologia 174:259–271. doi: 10.1007/s11046-012-9551-x. [DOI] [PubMed] [Google Scholar]
- 6.Khan Z, Ahmad S, Joseph L, Chandy R. 2012. Candida dubliniensis: an appraisal of its clinical significance as a bloodstream pathogen. PLoS One 7:e32952. doi: 10.1371/journal.pone.0032952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Ells R, Kock L, Pohl C. 2011. Candida albicans or Candida dubliniensis? Mycoses 54:1–16. doi: 10.1111/j.1439-0507.2009.01759.x. [DOI] [PubMed] [Google Scholar]
- 8.Loreto E, Scheid L, Nogueira C, Zeni G, Santurio J, Alves S. 2010. Candida dubliniensis: epidemiology and phenotypic methods for identification. Mycopathologia 169:431–443. doi: 10.1007/s11046-010-9286-5. [DOI] [PubMed] [Google Scholar]
- 9.Iwen PC, Freifeld AG, Bruening TA, Hinrichs SH. 2004. Use of a panfungal PCR assay for detection of fungal pathogens in a commercial blood culture system. J Clin Microbiol 42:2292–2293. doi: 10.1128/JCM.42.5.2292-2293.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.BioFire Diagnostics, Inc. 2014. FilmArray blood culture identification panel instructions for use. BioFire Diagnostics, Inc., Salt Lake City, UT. [Google Scholar]
