Ann Hematol (2001) 80:178–179
DOI 10.1007/s002770000252
C A S E R E P O RT
E. Gunsilius · C. Lass-Flörl · C.M. Kähler · G. Gastl
A.L. Petzer
Candida ciferrii, a new fluconazole-resistant yeast causing systemic
mycosis in immunocompromised patients
Received: 12 June 2000 / Accepted: 5 September 2000 / Published online: 10 January 2001
© Springer-Verlag 2001
Abstract Systemic infections related to fluconazole-
resistant yeasts are increasingly observed in immuno-
compromised patients receiving fluconazole as a prophy-
lactic antifungal treatment. Here, we report a case of in-
vasive candidiasis caused by Candida ciferrii in a patient
with acute myeloid leukemia and who suffered a relapse
after autologous peripheral blood progenitor cell trans-
plantation. Erythematous skin papulae and spotted pul-
monary infiltrations were present. A skin biopsy led to
the diagnosis of invasive candidiasis, emphasizing the
diagnostic usefulness of this procedure. The yeast was
identified as Candida ciferrii and in vitro susceptibility
testing revealed its resistance to fluconazole. Until now,
Candida ciferrii has not been known to cause invasive
fungal infections in humans. Thus, we add another fun-
gus to the list of flucanozole-resistant yeasts and suggest
that in vitro susceptibility testing of isolated fungi should
be performed for the selection of appropriate antimycotic
drugs.
Keywords Candida ciferrii · Fluconazole-resistance ·
Leukemia · PBPCT
Introduction
Fluconazole is frequently used for the prophylaxis of
fungal infections in patients who are immunosuppressed
after aggressive anti-neoplastic chemotherapy or because
E. Gunsilius (✉) · G. Gastl · A.L. Petzer
Division of Hematology & Oncology, University Hospital,
Anichstr. 35, 6020 Innsbruck, Austria
e-mail: eberhard.gunsilius@uibk.ac.at
Tel.: +43-512-5048668
C. Lass-Flörl
Department of Hygiene, University of Innsbruck, Innsbruck,
Austria
C.M. Kähler
Department of General Internal Medicine,
University of Innsbruck, Innsbruck, Austria
of infection with the human immunodeficiency virus.
Thus, infections caused by fluconazole-resistant fungi
may become a serious problem. Here, we report a case of
invasive candidiasis attributable to a fluconazole-resis-
tant strain of Candida ciferrii. This fungal species has
hitherto not been known to cause systemic infections in
immunodeficient patients.
Case report
A 62-year-old Caucasian man was diagnosed with acute myeloid
leukemia (AML, FAB-M1) in 1997. After induction chemothera-
py, complete remission was achieved, and filgrastim-mobilized
peripheral blood progenitor cells were harvested. Induction che-
motherapy was complicated by pulmonary aspergillosis, which
was successfully treated with intravenous amphotericin-B and sur-
gery. Ten months later, the patient suffered from a bone-marrow
relapse. He received busulphan (4 mg/kg p.o.) in divided doses
daily for 4 days (total dose 16 mg/kg) and etoposide (3000 mg i.v.,
single dose) and an autologous peripheral blood progenitor cell
transplant and experienced prompt trilineage engraftment without
complications in the early post-transplant period. Complete remis-
sion was documented by bone-marrow cytology. Ten months
thereafter, he presented with fever (up to 40°C) and pancytopenia
(WBC: 0.5 G/l, PLT: 25 G/l, Hb: 75 g/l) because of a second re-
lapse of his disease (95% immature myeloid blastic cells in a bone
marrow aspirate). He received intravenous ceftazidime, vancomy-
cin, and netilmicin, but the fever persisted. At that time, erythema-
tous skin papulae appeared on the lower extremities. A skin biop-
sy was performed, and the histological examination revealed pseu-
dohyphae. Concurrently, spotted pulmonary infiltrations were visi-
ble in a computerized tomography (CT) scan (Fig. 1) and, in con-
junction with the result of the skin biopsy, were strongly sugges-
tive of invasive candidiasis. Therapy with liposomal amphoteri-
cin-B was commenced. The clinical situation worsened, and C-re-
active protein rose to 27 mg/dl. Multiple blood cultures were ster-
ile. The patient died six weeks later from septic multiorgan failure.
At necropsy, two specimens (1 cm3) from lung tissue were taken,
aseptically transferred to culture media (Sabouraud broth contain-
ing chloramphenicol, gentamycin, and Sabouraud glucose agar;
Merck, Darmstadt, Germany) and incubated at 35°C for 5 days.
For the identification of yeast grown from necropsy speciemens,
we used the yeast identification system API 20 C AUX (Bio
Merieux, Austria), examined the assimilation reaction of carbon
compounds, and performed cultures on corn meal agar (Merck,
Darmstadt, Germany). The yeast was identified as Candida cifer-
rii (Api AUX 6751366). Isolates were then tested for drug sensi-

Fig. 1 CT scan of the right (R) hemithorax showing posterobasal
pulmonary infiltrates (arrow). Candida ciferrii was identified as
the causative agent
tivity by determining minimal inhibitory concentrations (MIC) of
amphotericin-B, fluconazole, and itraconazole with a macrodilu-
tion technique according to the Nosocomial National Committee
for Clinical Laboratory Standards (NCCLS), document M23-P [3].
The in vitro susceptibility testing revealed sensitivity to amphoter-
icin-B (MIC 0.5 µg/ml) and itraconazole (MIC 0.5 µg/ml), but re-
sistance to fluconazole (MIC >64 µg/ml).
Results and discussion
Since its first description by Kreger van Rij in 1965,
Candida ciferrii has not been known to cause deep-seat-
ed mycosis [2]. In humans, isolates have been drawn
mainly from the toe nails of elderly patients with trophic
179
disorders of the legs [1]. Knowledge of the natural habi-
tat of Candida ciferrii is limited. Systemic mycoses
cause substantial morbidity and mortality in immuno-
compromised patients, and fluconazole is increasingly
used as prophylaxis for fungal infections or for first-line
treatment of mucocutaneous candidiasis. Thus, one must
anticipate an increase of infections with azole-resistant
Candida albicans species and fluconazole-resistant
yeasts such as Candida krusei and Candida glabrata [4].
We describe here another fluconazole-resistant yeast,
Candida ciferrii, that can cause invasive mycosis in im-
munosuppressed hosts and that should be counted among
the emerging Candida pathogens. The histological exam-
ination of the skin biopsy performed in our patient indi-
cated systemic candidiasis, thus emphasizing the diag-
nostic importance of this procedure. The patient died
from his infection regardless of treatment with ampho-
tericin-B (a total dose of 5.3 g liposomal amphotericin-B
was given), which had previously been shown to be
highly active against the Candida ciferrii strain isolated
from autopsy specimens, indicating the limited predic-
tive value of in vitro susceptibility testing regarding clin-
ical outcome. However, because of the resistance of the
isolates to fluconazole, which confirms previous obser-
vations [1], susceptibility testing of clinical Candida iso-
lates seems mandatory.
References
1. Gentile L de, Bouchara JP, Le Clec’h C, Cimon B, Symoens F,
Chabasse D (1995) Prevalence of Candida ciferrii in elderly
patients with trophic disorders of the legs. Mycopathologia
131:99–102
2. Kreger-Van Rij NJ (1965) Candida ciferrii, a new yeast species.
Mycopathol Mycol Appl 26:49–52
3. National Committee for Clinical Laboratory Standards. Refer-
ence Method for Broth Dilution Susceptibility Testing of
Yeasts: Proposed Standard M27-A. NCCLS, Villanova, Pa.
4. Wingard JR, Merz WG, Rinaldi MG, Miller CB, Karp JE, Saral
R (1993) Association of Torulopsis glabrata infections with
fluconazole prophylaxis in neutropenic bone marrow transplant
patients. Antimicrob Agents Chemother 37:1847–1849