Invasive infection in an acute myeloblastic leukemia patient due to
triazole-resistant Candida tropicalis
Ana Maria Rabelo de Carvalho Parahyma, Carolina Maria da Silvaa,
Mariele Porto Carneiro Leãoa, Michele Chianca Macarioa,
Gustavo Antônio da Trindade Meira Henriques Filhob, Neiva Tinti de Oliveiraa,
Rejane Pereira Nevesa,⁎
aDepartamento de Micologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Av. Prof. Nelson Chaves, s/no- Cidade Universitária,
50670-420 Recife, Brazil
bIntensive Care Unit, Fundação de Hematologia e Hemoterapia de Pernambuco-HEMOPE, Rua Joaquim Nabuco, no 171, 55296-270 Recife, Brazil
Received 6 June 2011; accepted 2 August 2011
Non-albicans Candida species are being increasingly reported as causes of nosocomial fungal infections. For example, invasive
candidiasis caused by C. tropicalis has been associated with hematologic malignancies. In this study, we report a fatal case of fungemia and a
possible urinary and pulmonary infection in a leukemia patient that was due to a strain of C. tropicalis resistant to 2 triazole antifungals.
© 2011 Elsevier Inc.
Open access under the Elsevier OA license.
Keywords: Invasive candidiasis; Candida tropicalis; Antifungal susceptibility
1. Case report
A 68-year-old man being treated with chemotherapeutics
for acute myeloblastic leukemia (AML M2) was interned in
the intensive care unit (ICU) of the Foundation of
Hematology and Hemotherapy of Pernambuco, Recife,
Brazil. The patient received broad-spectrum antibiotics and
fluconazole at a dose of 400 mg/kg per day determined
empirically. Physical examination showed persistent fever,
hypotension, acute renal failure, pulmonary respiratory
failure with bilateral pleural effusion, and splenomegaly.
Laboratory findings using a hemogram showed 2200/mm3
leukocyte counts and 57,000/mm3platelet counts.
Samples of blood, tracheal secretions, and urine were
collected on 3 consecutive days. Venous blood samples were
collected aseptically from the central and peripheral veins by
venipuncture, tracheal secretion samples were obtained via
endotracheal aspiration, and urine specimens were collected
in aseptic tubes after the urinary catheter had been removed.
Because of thrombocytopenia and the severity of the patient,
it was not possible to perform lung and kidney biopsies. All
samples were processed immediately after collection by
standard methods of mycologic diagnosis.
Microbiological identification was achieved using tradi-
tional taxonomy according to the criteria described by
Barnett et al. (2000), through the CHROMagar Candida
(CHROMagar Company, Paris, France), a selective and
differential chromogenic medium, and by using species-
specific primer pairs for C. tropicalis (CTR22: 5′ TGG GCG
GTA GGA GAA TTG CGT TA 3′; NL4CTR1: 5′ TAA
GAT CAT TAT GCC AAC ATC CTA GGT ATA 3′).
Antifungal susceptibility testing was performed in accor-
dance with protocols defined by the Clinical and Laboratory
Standards Institute (CLSI) M27-A3 method (CLSI, 2008).
The antifungal drugs amphotericin B (United Medical-
Gilead, San Dimas, CA), anidulafungina (Pfizer, New York
Inc., NY), fluconazole (Pfizer), and voriconazole (Pfizer)
were tested. Quality control was performed by testing CLSI-
recommended strains C. tropicalis ATCC 750 and
C. parapsilosis ATCC 22019.
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The diagnosis was based on the detection of fungal
elements by direct examination (Fig. 1) and following the
isolation of the causal agent in pure culture from all samples.
The isolates were identified as C. tropicalis by standard
taxonomic methods, and the results of the molecular test are
shown in Fig. 2.
The isolation of C. tropicalis in blood cultures
confirmed a case of fungemia by this yeast. Owing to the
impossibility of performing lung and kidney biopsies, the
occurrence of disseminated fungal infection cannot be
proven. However, C. tropicalis was isolated from urine and
tracheal secretion, confirming a colonization of urinary and
pulmonary tract. This colonization was the presumed
source of infection associated with the occurrence of
fungemia. These results associated with clinical manifesta-
tions suggest an invasive infection.
Antifungal susceptibility tests were performed on the
isolates from the different samples. These showed similar
results, with average MICs for the 4 different antifungal
drugs determined as follows: amphotericin B 0.03 μg/mL;
anidulafungina 0.06 μg/mL; fluconazole 64 μg/mL; and
voriconazole 16 μg/mL. Thus, the isolates were sensitive
only to amphotericin B and anidulafungina. Accordingly,
amphotericin B (50 mg/kg per day) was administered
intravenously. However, the patient died of septic shock
15 days after the treatment was started.
The strains have been maintained at the URM Culture
Collection of the Department of Mycology, Federal
University of Pernambuco, Brazil, with record numbers
5872, 5873, and 5876.
Critically ill patients admitted to ICUs are at greatest risk
of fungal infections as a result of immunosuppression and
the frequent use of invasive devices (Pfaller and Diekema,
2007) such as venous and urinary catheters and nasogastric
tubes. In particular, C. tropicalis has been reported as an
important causative agent of invasive infection in patients
with hematologic malignancies (Nucci and Colombo, 2007).
In this study, we identified the species that caused the
candidiasis in a leukemia patient. The patient was treated
empirically with fluconazole, and resistance to 2 triazole
antifungals, fluconazole and voriconazole, was detected.
The extensive use of antifungals for prophylaxis has
become the leading cause of colonization by non-albicans
species and of increasing resistance to antifungal drugs. In
virtually every instance in which resistant C. tropicalis has
been observed, the patient has been on fluconazole
treatment (Leroy et al., 2009) and the development of
resistance to fluconazole often causes cross-resistance to
the whole triazole antifungal drugs (Chai et al., 2010).
The weakened immunity, high virulence, and low azole
susceptibility characteristics of C. tropicalis may be the
leading cause of disseminated candidiasis in patients with
hematologic malignancies (Kothavade et al., 2010).
To control nosocomial infections for drug-resistant strains
of C. tropicalis, rapid detection, followed by a drug
susceptibility test, needs to be performed on the clinical
isolates (Kothavade et al., 2010). Our results confirm that
early diagnosis and appropriate antifungal therapy are
important for a better prognosis.
In summary, C. tropicalis caused invasive candidiasis in
an AML M2 patient and the treatment of this infection with
Fig. 1. Direct examination revealed yeast cells in blood (A) and hyphae hyaline and yeast cells in tracheal secretion (B) and urine (C).
Fig. 2. Agarose gel electrophoresis of polymerase chain reaction products of
Candida isolates with species-specific primer for C. tropicalis CTR22 and
NL4CTR1. Lanes 1 to 5 correspond to isolates 5ST, 5U, 5S, ATCC 750
292A.M.R. de Carvalho Parahym et al. / Diagnostic Microbiology and Infectious Disease 71 (2011) 291–293
triazole antifungal drugs should be carried out with caution
in patients previously treated with these drugs. Ultimately,
testing for antifungal susceptibility is associated with
initiation of appropriate therapy and the reduction of
morbidity and mortality related to these infections.
The authors are particularly grateful to Dr. David
Bousfield for the critical reading of the manuscript and to
Conselho Nacional de Desenvolvimento Científico e
Tecnológico (CNPq) for financing the research.
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