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Case 3
The third patient was a 39-year-old black man from Baltimore who was admitted
for complications of end-stage liver disease,
including acute renal failure and ascites, and
diffuse lymphadenopathy of unknown etiology. He
also had a history of diabetes mellitus. A week
before hospitalization, the patient had been
discharged from another hospital, where he had
been admitted because of pancreatitis and treated
for Escherichia coli bacteremia and renal
insufficiency. The patient had a peripheral
intravenous catheter and a central venous catheter
placed during this hospitalization. On day 2,
yeasts were recovered from a peripheral blood
culture; these were later identified as C.
dubliniensis. By the time the result of the blood culture
was reported, the patient's clinical status had deteriorated because of worsening
respiratory distress. He was treated with fluconazole
400 mg/day for 3 days but died 5 days after the
blood culture was obtained. No autopsy was performed.
Case 4
The fourth case occurred in a 37-year-old white woman from Baltimore, who had a
history of intravenous drug use, chronic deep vein thrombosis, and valvular heart disease. She
was also HIV-infected (CD4+ lymphocyte count
was 779 cells/ml). She was hospitalized because of fever and chills, and blood cultures on day 1
of admission grew group A streptococci, for which she was treated with various antibiotics. On
day 7, fever developed and peripheral blood
cultures grew C. dubliniensis and C.
glabrata. She was treated with oral fluconazole 400 mg/day for
2 weeks and was discharged to a skilled-nursing facility 1 day after being started on
fluconazole.
Microbiologic Results
All seven isolates were originally
identified as C. albicans on the basis of their
phenotypic characteristics. They were reexamined at
the Fungus Reference Laboratory, Centers for Disease Control and Prevention, and
reidentified as C. dubliniensis on the basis of
biochemical and morphologic criteria (9). The
identification was confirmed by reactivity of DNA with
a polymerase chain reaction (PCR)-enzyme immunoassay (EIA) probe specific for this species
(10) and by PCR amplification of a region
containing the novel C. dubliniensis group I intron in
the large ribosomal subunit (11).
Broth microdilution MICs were determined according to National Committee for
Clinical Laboratory Standards document M27-A guidelines (12). All isolates were susceptible
to commonly used antifungal agents. MICs of amphotericin B were 0.25 (one patient)
to 0.5 µg/ml (three patients); MICs of
itraconazole were from <0.015 (two patients) to 0.03
µg/ml (two patients): and MICs of fluconazole
and flucytosine were <0.125 µg/ml for all isolates.
Conclusions
The incidence of candidemia due to C.
dubliniensis is not known, largely because of the difficulty in readily distinguishing
this species from the morphologically similar C.
albicans. However, in laboratory-based surveillance conducted in 1992-93 in two sites
in the United States (population 5.8 million), we
did not find C. dubliniensis as an agent of candidemia, even with the DNA-based
identification method used in this study (13).
More recently, three cases of C.
dubliniensis fungemia have been reported from Europe in patients
with chemotherapy-induced immunosuppression and bone marrow transplantation (8). The four
cases described here are the first reported in the United States.
The demonstration that C.
dubliniensis has the potential to cause bloodstream
infection provides information central to our
understanding of its clinical relevance and
pathogenic potential. As in the earlier European report (8), the patients in our study had multiple
serious medical conditions. Two of the four patients
had end-stage liver disease, which is a known risk factor for bloodstream infections with
organisms that are part of the normal gastrointestinal
flora because of breakdown of the normal mucosal barrier (14). This strongly suggests that
the gastrointestinal tract was the source of
the C. dubliniensis in these patients. Odds et al. (6) have reported the reidentification as C.
dubliniensis of a number of C. albicans isolates that were obtained from fecal
surveillance cultures in hematologic patients.
The isolation of C. dubliniensis from
mucosal sites in HIV-infected persons has been
widely reported (3,5). Although not severely
immunocompromised, our fourth patient
was HIV-positive, which makes hers the first reported case of bloodstream infection with
this organism in an HIV-infected person. The fact that
C. dubliniensis is able to cause invasive disease in these patients is of clinical
interest. However, it may be more significant
that C. glabrata, a recognized pathogen, was
also isolated from blood cultures in our patient.
As our population-based surveillance for candidemia continues, we will be able to
estimate more accurately the incidence of candidemia
due to C. dubliniensis and define more clearly
its clinical importance, epidemiologic characteristics, and outcome. The specific
proportional impact of C. dubliniensis candidemia on
outcome is difficult to assess in these patients, all of
whom had multiple underlying conditions. The organisms isolated from our patients were all
fully susceptible to amphotericin B, flucytosine, fluconazole, and itraconazole. However,
resistance has been shown to occur in HIV-positive patients given fluconazole treatment for
oral infection with C. dubliniensis (7). As
our knowledge about this emerging pathogenic yeast increases and diagnostic tests are
developed, prevention and better management of the disease will become possible.
Acknowledgment
We thank the laboratory participants who
collected isolates for this study.
Dr. Brandt is a research microbiologist in the
Mycotic Diseases Branch, Division of Bacterial and
Mycotic Diseases, CDC. She and Dr. Hajjeh are members
of the CDC Fungal Active Surveillance Group, which
conducts active population-based surveillance for fungal
diseases of public health importance.
Address for correspondence: Mary E. Brandt, Mycotic
Diseases Branch, Centers for Disease Control and Prevention,
1600 Clifton Road, Mailstop G11, Atlanta, GA 30333, USA; fax:
404-639-3546; e-mail: mbb4@cdc.gov
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1For the CDC Candidemia Surveillance Group, which includes W. Ruth Pruitt, Nathelia
LeSane, Gabriel Ponce de Leon,
Meral Ciblak, G. Marshall Lyon (CDC); Laurie Thomson Sanza (Maryland); Lily Yeo and Brian Wong (Connecticut).
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