Candida dubliniensis: An Appraisal of Its Clinical Significance as a Bloodstream Pathogen
Citation: Khan Z, Ahmad S, Joseph L, Chandy R (
Candida dubliniensis : An Appraisal of Its Clinical Significance as a Bloodstream Pathogen
Ziauddin Khan 0
Suhail Ahmad 0
Leena Joseph 0
Rachel Chandy 0
Scott G. Filler, David Geffen School of Medicine at University of California Los Angeles, United States of America
0 Department of Microbiology, Faculty of Medicine, Kuwait University , Safat , Kuwait
A nine-year prospective study (2002-2010) on the prevalence of Candida dubliniensis among Candida bloodstream isolates is presented. The germ tube positive isolates were provisionally identified as C. dubliniensis by presence of fringed and rough colonies on sunflower seed agar. Subsequently, their identity was confirmed by Vitek2 Yeast identification system and/or by amplification and sequencing of the ITS region of rDNA. In all, 368 isolates were identified as C. dubliniensis; 67.1% came from respiratory specimens, 11.7% from oral swabs, 9.2% from urine, 3.8% from blood, 2.7% from vaginal swabs and 5.4% from other sources. All C. dubliniensis isolates tested by Etest were susceptible to voriconazole and amphotericin B. Resistance to fluconazole ($8 mg/ml) was observed in 2.5% of C. dubliniensis isolates, 7 of which occurred between 20082010. Of note was the diagnosis of C. dubliniensis candidemia in 14 patients, 11 of them occurring between 2008-2010. None of the bloodstream isolate was resistant to fluconazole, while a solitary isolate showed increased MIC to 5-flucytosine (.32 mg/ml) and belonged to genotype 4. A review of literature since 1999 revealed 28 additional cases of C. dubliniensis candidemia, and 167 isolates identified from blood cultures since 1982. In conclusion, this study highlights a greater role of C. dubliniensis in bloodstream infections than hitherto recognized.
Competing Interests: The authors have declared that no competing interests exist.
Candida dubliniensis was first described in 1995 from oral
cavities of human immunodeficiency virus (HIV)-infected
individuals . The species forms only a minor component of normal
microbiota but has a worldwide distribution . Despite its close
relationship with C. albicans, which is the predominant pathogenic
species, the etiopathologic role of C. dubliniensis has mostly been
restricted to oral candidiasis. In recent years, however, C.
dubliniensis has increasingly been reported from patients with
candidemia . Although the species is significantly less
virulent and genetically more clonal than C. albicans , the
reasons for its expanding role in invasive disease remain largely
unknown. Here, we report the prevalence of C. dubliniensis in
various clinical specimens over a nine-year period and discuss its
role in nosocomial candidemia.
Materials and Methods
C. dubliniensis isolates and their identification
The study was carried out at Mycology Reference Laboratory
(MRL) (Department of Microbiology, Faculty of Medicine,
Kuwait University) and included all Candida spp. isolates obtained
between 20022010. Candida spp. isolates either received from 15
different hospitals within Kuwait for identification and antifungal
susceptibility testing or recovered from various clinical specimens
at MRL were prospectively tested for germ tube formation. All
germ tube positive isolates were streaked on sunflower seed agar
 and incubated for 48 h at 30uC for formation of fringed and
rough colonies and chlamydospore production. Subsequently,
their identity was also confirmed by Vitek2 Yeast identification
system and/or by amplification and sequencing of the ITS region
of rDNA [16,17]. The study was approved by the Ethical
Committee of Health Sciences Center and Ministry of Health.
Molecular identification, genotype determination and
detection of 5-flucytosine resistance
The genotypes of C. dubliniensis isolates based on internal
transcribed spacer (ITS) region of rDNA were determined by PCR
amplification with genotype-specific primers and DNA sequencing
as described previously [18,19]. PCR products (10 ml) were
resolved by electrophoresis in 2% (wt/vol) agarose gels and
presence of a single amplicon of expected size indicated the
specific genotype. The results were extended by direct DNA
sequencing of the ITS region (containing ITS-1, 5.8S rRNA and
ITS-2) of rDNA. The amplicons obtained with ITS1 and ITS4
panfungal primers were purified and both strands were sequenced
using BigDye terminator v3.1 cycle sequencing kit and ABI 3130xl
GeneticAnalyzer (Applied Biosystems Inc.). The ITS1FS, ITS2,
ITS3 and ITS4RS were used as sequencing primers [19,20].
Specific genotypes were assigned based on maximum identity in
BLAST searches . The detection of 5-flucytosine
resistanceconferring mutations in CdFCA1 gene codon 29 was carried out by
PCR amplification using FCA1F and FCA1R primers, the
amplicons were purified and subjected to restriction digestion
with Mbo I to generate RFLP patterns or sequenced as described
previously [18,22]. Pair-wise comparisons with sequences of
5-FCsusceptible and 5-FC-resistant C. dubliniensis isolates were
performed using ClustalW.
Susceptibility testing by E-test
Antifungal susceptibility by E-test was performed on RPMI
1640 agar medium supplemented with 2% glucose with pH
adjusted to 7.0 with 0.165 M MOPS buffer as described
previously . Etest strips for fluconazole, amphotericin B, and
5- fluorocytosine were obtained from AB BIODISK (Solna,
Sweden). The test was performed according to manufacturers
instructions. Briefly, 140 mm diameter petri plates were poured
with 60 ml RPMI medium containing 1.5% agar and allowed to
solidify. The agar surface was uniformly inoculated by nontoxic
cotton swab dipped in yeast cell suspension of the test isolates after
adjusting their turbidity to 0.5 McFarland standard. The plates for
minimum inhibitory concentration (MIC) were read after 24 h of
incubation at 35uC. The MICs were determined at the lowest drug
concentrations at which the border of the elliptical inhibition zone
intersected the strip scale. Reference strains of C. krusei (ATCC
6258), C. parapsilosis (ATCC22019) and C. albicans (ATCC90028)
were used for quality control. The resistance to fluconazole
($8 mg/ml) was determined by applying revised CLSI/EUCAST
Mann-Whitney test was applied to determine significance of
differences observed in mean MIC values of fluconazole during
the three sub-periods of the study (2002 to 2004, 2005 to 2007,
and 2008 to 2010). SPSS version 17.0 was used for statistical
analysis and a P value of ,0.05 was considered as significant.
During the 9-year study period (20022010), 368 isolates of C.
dubliniensis were prospectively identified. These included 54
(14.7%) isolates during 20022004, 150 (40.7) isolates during
20052007, and 164 (44.6%) isolates during 20082010. Of these,
247 (67.1%) came from respiratory (sputum and endotracheal
secretions) specimens, 43 (11.7%) from oral swabs, 34 (9.2%) from
urine, 14 (3.8%) from blood, 10 (2.7%) from vaginal swabs and 20
(5.4%) from other specimens. Of the 121 isolates (including all
bloodstream isolates) genotyped, 82 belonged to genotype 1 and
38 isolates belonged to genotype 4. The remaining isolates
belonged to genotypes 59 . All 38 isolates belonging to
genotype 4 were resistant to 5-flucytosine and contained S29L
mutation at codon 29 of CdFCA1 gene [18,22]. Of note was the
enhanced frequency of isolation of C. dubliniensis from 14 blood
specimens obtained from 14 patients. Of the total of 1154 Candida
spp. blood culture isolates received, the distribution of C.
dubliniensis during the three sub-periods of the study was as
follows: one of 244 (0.4%) between 20022004, two of 356 (0.6%)
between 20052007, and 11 of 554 (2%) between 20082010
(Table 1). All C. dubliniensis candidemia patients were diagnosed at
different time points during the indicated periods.
The particulars of 11 patients yielding C. dubliniensis in blood
cultures whose records were available for review are presented in
Table 2. All patients were immunocompromised and had one or
more risk factors. Three of them occurred in males. Their age
ranged from 485 years. Four of the patients were treated with
fluconazole, two each with voriconazole and amphotericin B (lipid
formulation) and one with caspofungin. All blood culture isolates
were susceptible to fluconazole, amphotericin B and caspofungin.
A solitary blood culture isolate was resistant to 5-flucytosine and
belonged to genotype 4. Four of the patients (Cases 1, 7, 10 and
Table 1. Occurrence of C. dubliniensis among bloodstream
isolates of Candida spp.
Candida spp. isolates
No. (%) of
C. dubliniensis isolates
11) died, two of them before the blood cultures became positive,
hence no antifungal therapy was administered. C. dubliniensis was
the only pathogen isolated from blood culture of two of these four
The data on MIC50, MIC90, MIC range and geometric mean
of MICs of C. dubliniensis isolates are presented in Table 3. All C.
dubliniensis isolates that were available for testing were susceptible
to amphotericin B and voriconazole. Eight (2.5%) isolates were
resistant to fluconazole with MICs ranging between $8 mg/ml to
32 mg/ml . There was marginal increase in geometric mean of
MIC values of fluconazole during the three sub-periods of the
study: 20022004 (n = 54), 0.224 mg/ml; 20052007 (n = 131),
0.307 mg/ml; and 20082010 (n = 135), 0.338 mg/ml. These
differences in mean MICs were not significant (p = 0.219). As
many as 60 isolates (10 of 54 during 20022004, 29 out of 109 in
20052007 and 21 out of 86 in 20082010) were resistant to
5flucytosine and all 38 that were sequenced belonged to genotype 4
The true prevalence of C. dubliniensis fungemia largely remains
unknown because of the difficulty in readily distinguishing this
species from the morphologically similar species, C. albicans. This
study is noteworthy as it prospectively identified all germ tube
positive Candida bloodstream isolates for the presence of C.
dubliniensis. We observed that prevalence of C. dubliniensis among
bloodstream isolates increased from 0.4% between 20022004 to
2% between 20082010 (Table 1). The reasons for increased
occurrence of candidemia cases due to C. dubliniensis are unclear.
Bloodstream C. dubliniensis isolates formed 3.8% (14 of 368) of the
total isolates of this species recovered from all clinical specimens.
In a previous study from Saudi Arabia, the overall prevalence of C.
dubliniensis was 3.3% among 823 yeast isolates recovered from
different clinical specimens . Two (16.7%) of their
bloodstream isolates were re-identified as C. dubliniensis. Several
retrospective and prospective studies published during 2002
2011 have reported on the prevalence of C. dubliniensis among
bloodstream Candida spp. isolates (Table S1) [6,10,2442].
Generally, the prevalence of C. dubliniensis varied between 0.5%
to 7.0% with the exception of two studies involving small number
of isolates [24,31], where it was 16.7% and 10.0%, respectively. In
these two studies, only germ tube positive bloodstream isolates
were included. In a recent fungemia surveillance study from
Denmark, Arendrup et al.  reported a prevalence of 1.2% to
3.1% over a six-year period and 74 (2.6%) of C. dubliniensis isolates
came from blood cultures.
Since the first description of C. dubliniensis from oral cavities of
HIV-positive patients from Ireland [1,43], subsequent
epidemiological studies have revealed that this species is prevalent globally
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Table 3. Antifungal susceptibility profile of Candida
*Geometric mean for flucytosine resistant isolates was calculated at 32 mg/ml.
The numbers of the resistant isolates for the three periods were 10, 29, and 21,
respectively. Numbers in parentheses indicate isolates with MIC $8 mg/ml .
aNumber of isolates tested.
in association with human  and non-human habitats with a
possibility of inter-host transmission [44,45]. The species has now
been reported from other body sites/specimens, such as vagina,
urine, skin, and feces/gastrointestinal tract of both HIV-positive
and HIV-negative patients [2,16,17,46,47]. There are now
increasing reports that C. dubliniensis has the potential to cause
invasive disease in different groups of immunocompromised
patients , possibly originating from hosts own flora. Although
C. dubliniensis is closely related to C. albicans, it is responsible for far
fewer infections in humans. It is rare that patients colonized with
this species develop candidemia . The reasons for this limited
ability of C. dubliniensis to cause invasive disease has been the focus
of recent studies . It has been shown that C. dubliniensis
genome lacks important hypha-related virulence genes (e.g., ALS3
and HYR1) and it also has limited ability to undergo
yeast-tohyphal transformation [49,50], which in turn may affect its
potential to invade deeper tissue.
A review of literature since 1999 revealed 32 cases of
bloodstream infection due to C. dubliniensis [3,4,69,25,42,51
59]. They originated from different geographic regions (Europe-8,
North America-17, Argentina-4, Australia-2, Singapore-1). All of
them had underlying conditions or risk factors including six with
HIV infection. Their ages ranged between 168 years. Of 28
patients for whom detailed particulars were available (Table S2),
15 were males. Six of these cases occurred in pediatric age group
and 14 of 28 (50%) patients died. In three of them, no antifungal
agent was administered. One patient died due to
rhabdomyosarcoma despite receiving treatment with fluconazole. It is
noteworthy that first of the three cases of C. dubliniensis fungemia were
reported from Europe in non-HIV-infected patients with bone
marrow transplantation and chemotherapy-induced neutropenia
. This was followed by a report of four additional cases from the
United States including one who was infected with HIV . This
was believed to be the first case of C. dubliniensis candidemia in
HIV-infected patient. Subsequently, 21 additional cases of C.
dubliniensis fungemia were reported from many other countries
(Table S2). However, the isolation of nearly 200 strains of C.
dubliniensis from blood indicates that 28 described cases of
candidemia represent only a fraction of total candidemia cases
caused by this species. Furthermore, since blood culture positivity
from candidemia patients seldom exceeds 50%, C. dubliniensis may
be responsible for far greater number of candidemia cases than
All our C. dubliniensis isolates were susceptible to voriconazole
and amphotericin B. However, 2.5% (8 out of 320) of the isolates
were considered resistant (MICs$8 mg/ml) according to
harmonized CLSI and EUCAST susceptibility breakpoints for Candida
spp., which do not include C. dubliniensis . It is noteworthy that
none of the 11 C. dubliniensis bloodstream isolates was resistant to
fluconazole. Generally, C. dubliniensis isolates are known to be
susceptible to a wide range of antifungal agents . Recently,
Arendrup et al.  reported occurrence of fluconazole resistance
in 3.1% (2 of 65) of C. dubliniensis bloodstream isolates using
EUCAST breakpoint (MIC.4 mg/ml). It is unclear if marginal
increase in fluconazole MICs (as indicated by geometric mean,
Table 3) in the present study have in any manner contributed to
increased occurrence of C. dubliniensis candidemia during 2008
2010. In this context, a reference may be made to a recent
publication by Oxman et al. , who found that a significant
number of candidemia episodes were caused by isolates that
showed reduced susceptibility to fluconazole while still considered
to be fully susceptible. Although none of our candidemia patient
was on fluconazole prophylaxis, it has been shown that exposure to
fluconazole may enhance adherence of C. dubliniensis to oral
epithelium  and may also facilitate replacement of C. albicans
with C. dubliniensis . The impact of fluconazole therapy/
prophylaxis on the epidemiology C. dubliniensis candidemia is not
known. Some investigators believe that widespread exposure to
azoles may have contributed to increasing incidence of less
susceptible non-albicans Candida spp. as bloodstream pathogens
, a view that has not been shared by others .
In conclusion, a 9-year prospective study on the prevalence of C.
dubliniensis among bloodstream Candida spp. isolates with an overall
prevalence of 1.2%, is presented. Of 14 cases of C. dubliniensis
candidemia, 11 were diagnosed between 20082010, thus
highlighting an increasing role of C. dubliniensis in bloodstream
infections in Kuwait in recent years. These observations are
consistent with the global trend pointing towards changing
epidemiology of candidemia in favor of non-albicans Candida spp.
Table S1 Prevalence of C. dubliniensis among bloodstream
isolates of Candida spp.
Summary of published case reports of C. dubliniensis
Technical assistance of Ajmal Theyyathel is acknowledged.
Conceived and designed the experiments: ZK. Performed the experiments:
LJ RC. Analyzed the data: ZK SA. Contributed reagents/materials/
analysis tools: ZK SA. Wrote the paper: ZK SA.
1. Sullivan DJ , Westerneng TJ , Haynes KA , Bennett DE , Coleman DC ( 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 .
2. Loreto ES , Scheid LA , Nogueira CW , Zeni G , Santurio JM , et al. ( 2010 ) Candida dubliniensis: epidemiology and phenotypic methods for identification . Mycopathologia 169 : 431 - 443 .
3. Brandt ME , Harrison LH , Pass M , Sofair AN , Huie S , et al. ( 2000 ) Candida dubliniensis fungemia: the first four cases in North America . Emerg Infect Dis 6 : 46 - 49 .
4. Fanci R ( 2009 ) Breakthrough Candida dubliniensis fungemia in an acute myeloid leukemia patient during voriconazole therapy successfully treated with caspofungin . J Chemother 21 : 105 - 107 .
5. Horn DL , Neofytos D , Anaissie EJ , Fishman JA , Steinbach WJ , et al. ( 2009 ) Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry . Clin Infect Dis 48 : 1695 - 1703 .
6. Jabra-Rizk MA , Johnson JK , Forrest G , Mankes K , Meiller TF , et al. ( 2005 ) Prevalence of Candida dubliniensis fungemia at a large teaching hospital . Clin Infect Dis 41 : 1064 - 1067 .
7. Marriott D , Laxton M , Harkness J ( 2001 ) Candida dubliniensis candidemia in Australia . Emerg Infect Dis 7 : 479 p.
8. Meis JF , Ruhnke M , De Pauw BE , Odds FC , Siegert W , et al. ( 1999 ) Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation . Emerg Infect Dis 5 : 150 - 153 .
9. Mubareka S , Vinh DC , Sanche SE ( 2005 ) Candida dubliniensis bloodstream infection: a fatal case in a lung transplant recipient . Transpl Infect Dis 7 : 146 - 149 .
10. Silva V , Cabrera M , Daz MC , Abarca C , Hermosilla G ( 2003 ) [Prevalence of Candida albicans serotypes in blood isolates in Chile, and first report of Candida dubliniensis candidemia] . Rev Iberoam Micol 20 : 46 - 51 .
11. van Hal SJ , Stark D , Harkness J , Marriott D ( 2008 ) Candida dubliniensis meningitis as delayed sequela of treated C. dubliniensis fungemia . Emerg Infect Dis 14 : 327 - 329 .
12. Coleman DC , Moran GP , McManus BA , Sullivan DJ ( 2010 ) Mechanisms of antifungal drug resistance in Candida dubliniensis . Future Microbiol 5 : 935 - 949 .
13. McManus BA , Coleman DC , Moran G , Pinjon E , Diogo D , et al. ( 2008 ) Multilocus sequence typing reveals that the population structure of Candida dubliniensis is significantly less divergent than that of Candida albicans . J Clin Microbiol 46 : 652 - 664 .
14. Sullivan DJ , Moran GP ( 2011 ) Differential virulence of Candida albicans and C. dubliniensis: a role for Tor1 kinase? Virulence 2 : 77 - 81 .
15. Khan ZU , Ahmad S , Mokaddas E , Chandy R ( 2004 ) Simplified sunflower (Helianthus annuus) seed agar for differentiation of Candida dubliniensis from Candida albicans . Clin Microbiol Infect 10 : 590 - 592 .
16. Ahmad S , Khan Z , Mokaddas E , Khan ZU ( 2004 ) Isolation and molecular identification of Candida dubliniensis from non-human immunodeficiency virusinfected patients in Kuwait . J Med Microbiol 53 : 633 - 637 .
17. Al-Sweih N , Ahmad S , Khan ZU , Khan S , Chandy R ( 2005 ) Prevalence of Candida dubliniensis among germ tube-positive Candida isolates in a maternity hospital in Kuwait . Mycoses 48 : 347 - 351 .
18. Ahmad S , Khan ZU , Joseph L , Asadzadeh M , Theyyathel T ( 2011 ) Genotypic heterogeneity and molecular basis of 5-flucytosine resistance among Candida dubliniensis isolates recovered from clinical specimens in Kuwait . Med Mycol Sep 6DOI: 10 .3109/13693786.2011. 597446 [Epub ahead of print] .
19. Khan ZU , Ahmad S , Hagen F , Fell JW , Kowshik T , et al. ( 2010 ) Cryptococcus randhawai sp. nov., a novel anamorphic basidiomycetous yeast isolated from tree trunk hollow of Ficus religiosa (peepal tree) from New Delhi , India. Antonie Van Leeuwenhoek 97 : 253 - 259 .
20. Khan ZU , Ahmad S , Mokaddas E , Chandy R , Cano J , et al. ( 2008 ) Actinomucor elegans var. kuwaitiensis isolated from the wound of a diabetic patient . Antonie Van Leeuwenhoek 94 : 343 - 352 .
21. Gee SF , Joly S , Soll DR , Meis JF , Verweij PE , et al. ( 2002 ) Identification of four distinct genotypes of Candida dubliniensis and detection of microevolution in vitro and in vivo . J Clin Microbiol 40 : 556 - 574 .
22. McManus BA , Moran GP , Higgins JA , Sullivan DJ , Coleman DC ( 2009 ) A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for cladespecific flucytosine resistance in Candida dubliniensis . Antimicrob Agents Chemother 53 : 4678 - 4685 .
23. Pfaller MA , Andes D , Diekema DJ , Espinel-Ingroff A , Sheehan D , CLSI Subcommittee for Antifungal Susceptibility Testing ( 2010 ) Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods . Drug Resist Update 13 : 180 - 195 .
24. Fotedar R , Al-Hedaithy SS ( 2003 ) Candida dubliniensis at a university hospital in Saudi Arabia . J Clin Microbiol 41 : 1907 - 1911 .
25. Cimolai N , Davis J , Trombley C ( 2002 ) Candida dubliniensis fungemia and vascular access infection . J Pediatr Hematol Oncol 24 : 237 - 239 .
26. Kibbler CC , Seaton S , Barnes RA , Gransden WR , Holliman RE , et al. ( 2003 ) Management and outcome of bloodstream infections due to Candida species in England and Wales . J Hosp Infect 54 : 18 - 24 .
27. Al-Hedaithy SS ( 2003 ) The yeast species causing fungemia at a university hospital in Riyadh, Saudi Arabia, during a 10-year period . Mycoses 46 : 293 - 298 .
28. Sancak B , Rex JH , Paetznick V , Chen E , Rodriguez J ( 2003 ) Evaluation of a method for identification of Candida dubliniensis bloodstream isolates . J Clin Microbiol 41 : 489 - 491 .
29. Tortorano AM , Caspani L , Rigoni AL , Biraghi E , Sicignano A , et al. ( 2004 ) Candidosis in the intensive care unit: a 20-year survey . J Hosp Infect 57 : 8 - 13 .
30. Hajjeh RA , Sofair AN , Harrison LH , Lyon GM , Arthington-Skaggs BA , et al. ( 2004 ) Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program . J Clin Microbiol 42 : 1519 - 1527 .
31. Tay ST , Chai HC , Na SL , Ng KP ( 2005 ) Molecular subtyping of clinical isolates of Candida albicans and identification of Candida dubliniensis Malaysia . Mycopathologia 159 : 325 - 329 .
32. Tekeli A , Akan OA , Koyuncu E , Dolapci I , Uysal S ( 2006 ) Initial Candida dubliniensis isolate in Candida spp. positive haemocultures in Turkey between 2001 and 2004 . Mycoses 49 : 60 - 64 .
33. Metwally L , Walker MJ , Coyle PV , Hay RJ , Hedderwick S , et al. ( 2007 ) Trends in candidemia and antifungal susceptibility in a university hospital in Northern Ireland 2001-2006 . J Infect 55 : 174 - 178 .
34. Odds FC , Hanson MF , Davidson AD , Jacobsen MD , Wright P , et al. ( 2007 ) One year prospective survey of Candida bloodstream infections in Scotland . J Med Microbiol 56 : 1066 - 1075 .
35. Asmundsdo ttir LR , Erlendsdo ttir H , Haraldsson G , Guo H , Xu J , et al. ( 2008 ) Molecular epidemiology of candidemia: evidence of clusters of smoldering nosocomial infections . Clin Infect Dis 47 : e17 - e24 .
36. Chen SC , Marriott D , Playford EG , Nguyen Q , Ellis D , et al. ( 2009 ) Candidaemia with uncommon Candida species: predisposing factors, outcome, antifungal susceptibility, and implications for management . Clin Microbiol Infect 15 : 662 - 669 .
37. Chen S , Slavin M , Nguyen Q , Marriott D , Playford EG , et al. ( 2006 ) Active surveillance for candidemia , Australia. Emerg Infect Dis 12 : 1508 - 1516 .
38. van Hal SJ , Marriott DJ , Chen SC , Nguyen Q , Sorrell TC , et al. ( 2009 ) Candidemia following solid organ transplantation in the era of antifungal prophylaxis: the Australian experience . Trans Infect Dis 11 : 122 - 127 .
39. Slavin MA , Sorrell TC , Marriott D , Thursky KA , Nguyen Q , et al. ( 2010 ) Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death . J Antimicrob Chemother 65 : 1042 - 1051 .
40. Dimopoulos G , Ntziora F , Rachiotis G , Armaganidis A , Falagas ME ( 2008 ) Candida albicans versus non-albicans intensive care unit-acquired bloodstream infections: differences in risk factors and outcome . Anesth Analg 106 : 523 - 529 .
41. Arendrup MC , Bruun B , Christensen JJ , Fuursted K , Johansen HK , et al. ( 2011 ) National surveillance of fungemia in Denmark (2004 to 2009) . J Clin Microbiol 49 : 325 - 334 .
42. Bosco-Borgeat ME , Taverna CG , Cordoba S , Isla MG , Murisengo OA , et al. ( 2011 ) Prevalence of Candida dubliniensis fungemia in Argentina: identification by a novel multiplex PCR and comparison of different phenotypic methods . Mycopathologia 172 : 407 - 414 .
43. Sullivan D , Coleman D ( 1997 ) Candida dubliniensis: an emerging opportunistic pathogen . Curr Top Med Mycol 8 : 15 - 25 .
44. McManus BA , Sullivan DJ , Moran GP , d'Enfert C , Bougnoux ME , et al. ( 2009 ) Genetic differences between avian and human isolates of Candida dubliniensis . Emerg Infect Dis 15 : 1467 - 1470 .
45. Nunn MA , Schaefer SM , Petrou MA , Brown JR ( 2007 ) Environmental source of Candida dubliniensis . Emerg Infect Dis 13 : 747 - 750 .
46. Gutierrez J , Morales P , Gonzalez MA , Quindo s G ( 2002 ) Candida dubliniensis, a new fungal pathogen . J Basic Microbiol 42 : 207 - 227 .
47. Mokaddas E , Khan ZU , Ahmad S ( 2011 ) Prevalence of Candida dubliniensis among cancer patients in Kuwait: a 5-year retrospective study . Mycoses 54 : e29 - e34 .
48. Jackson AP , Gamble JA , Yeomans T , Moran GP , Saunders D , et al. ( 2009 ) Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans . Genome Res 19 : 2231 - 2244 .
49. Moran GP , Coleman DC , Sullivan DJ ( 2011 ) Candida albicans versus Candida dubliniensis: why is C. albicans more pathogenic? Int J MicrobiolDoi:10.115/ 2012 / :205921. Epub 2011 Sep 4.
50. Stokes C , Moran GP , Spiering MJ , Cole GT , Coleman DC , et al. ( 2007 ) Lower filamentation rates of Candida dubliniensis contribute to its lower virulence in comparison with Candida albicans . Fungal Genet Biol 44 : 920 - 931 .
51. Sebti A , Kiehn TE , Perlin D , Chaturvedi V , Wong M , et al. ( 2001 ) Candida dubliniensis at a cancer center . Clin Infect Dis 32 : 1034 - 1038 .
52. Gottlieb GS , Limaye AP , Chen YC , Van Voorhis WC ( 2001 ) Candida dubliniensis fungemia in a solid organ transplant patient: case report and review of the literature . Med Mycol 39 : 483 - 485 .
53. McMullan R , Xu J , Moore JE , Millar BC , Walker MJ , et al. ( 2002 ) Candida dubliniensis bloodstream infection in patients with gynaecological malignancy . Eur J Clin Microbiol Infect Dis 21 : 635 - 636 .
54. Tan AL , Wang GC , Chiu YW ( 2002 ) Candida dubliniensis infection, Singapore . Emerg Infect Dis 8 : 445 - 446 .
55. Boyle BM , Sullivan DJ , Forkin C , Mulcahy F , Keane CT , et al. ( 2002 ) Candida dubliniensis candidaemia in an HIV-positive patient in Ireland . Int J STD AIDS 13 : 55 - 57 .
56. Kim JO , Garofalo L , Blecker-Shelly D , McGowan KL ( 2003 ) Candida dubliniensis infections in a pediatric population: retrospective identification from clinical laboratory isolates of Candida albicans . J Clin Microbiol 41 : 3354 - 3357 .
57. Carr MJ , Clarke S , O'Connell F , Sullivan DJ , Coleman DC , et al. ( 2005 ) First reported case of endocarditis caused by Candida dubliniensis . J Clin Microbiol 43 : 3023 - 3026 .
58. Chan-Tack KM ( 2005 ) Fatal Candida dubliniensis septicemia in a patient with AIDS . Clin Infect Dis 40 : 1209 - 1210 .
59. Baradkar VP , Mathur M , Kumar S ( 2008 ) Neonatal septicaemia in a premature infant due to Candida dubliniensis . Indian J Med Microbiol 26 : 382 - 385 .
60. Oxman DA , Chow JK , Frendl G , Hadley S , Hershkovitz S , et al. ( 2010 ) Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern ? J Antimicrob Chemother 65 : 1460 - 1465 .
61. Zepelin MB , Niederhaus T , Gross U , Seibold M , Monod M , et al. ( 2002 ) Adherence of different Candida dubliniensis isolates in the presence of fluconazole . AIDS 16 : 1237 - 1244 .
62. Martinez M , Lopez-Ribot JL , Kirkpatrick WR , Coco BJ , Bachmann SP , et al. ( 2002 ) Replacement of Candida albicans with C. dubliniensis in Human Immunodeficiency Virus infected patients with oropharyngeal candidiasis treated with fluconazole . J Clin Microbiol 40 : 3135 - 3139 .
63. Abi-Said D , Anaissie E , Uzun O , Raad I , Pinzcowski H , et al. ( 1997 ) The epidemiology of hematogenous candidiasis caused by different Candida species . Clin Infect Dis 24 : 1122 - 1128 .
64. Pfaller MA , Diekema DJ ( 2007 ) Epidemiology of invasive candidiasis: a persistent public health problem . Clin Microbiol Rev 20 : 133 - 163 .