Successful treatment of Trichosporon mucoides infection with lipid ...

Letter to the editor
Successful treatment of Trichosporon mucoides infection with lipid
complex amphotericin B and 5-fluorocytosine
Tanil Kendirli, 1 Ergin Ciftçi, 2 Erdal _ Ince, 2 Selim Öncel, 2 Nazan Dalgiç, 2 Haluk Güriz, 3 Emel Unal 4
and Ulker Dogru 2
Divisions of 1 Pediatric Intensive Care Unit, 2 Pediatric Infectious Diseases, 3 Pediatric Microbiology Laboratory and 4 Pediatric Oncology, Department of Pediatrics,
Ankara University School of Medicine, Ankara, Turkey
Summary Infections in immunocompromised children can stem from bacteria, fungi, viruses, or
protozoa, but most importantly, from the host’s endogenous bacterial flora.
Disseminated infection caused by Trichosporon species is one of the emerging mycoses
in neutropenic patients, particularly when they are treated for haematological
malignancy with cytotoxic and immunosuppressive chemotherapy. We report a 15year-old
boy with acute lymphoblastic leukaemia, whose Trichosporon mucoides infection
was successfully treated with lipid complex amphotericin B plus 5-fluorocytosine.
Key words: Trichosporon mucoides, sepsis, lipid complex amphotericin B, 5-fluorocytosine.
Introduction
The genus Trichosporon includes approximately 30
species, at least six of which (T. asahii, T. mucoides,
T. inkin, T. asteroides, T. cutaneum and T. ovoides) are
associated with infection (trichosporonosis). 1 The first
two species mentioned are responsible for deep infections
and the last four are involved in superficial
infections, including white piedra. Trichosporon asahii,
which is responsible for >90% of deep-seated trichosporonoses,
may cause a life-threatening illness. 1–3
These fungi are also normal inhabitants of the soil
and are occasionally found in the normal flora of the
skin and the mouth. Most patients with deep-seated
trichosporonosis have an underlying haematological
malignancy or another neoplasm. Neutropenia as the
result of cytotoxic chemotherapy is the most common
apparent risk factor for this infection. In immunosuppressed
individuals, Trichosporon infections may
disseminate to multiple organs, such as liver, spleen,
lungs and gastrointestinal tract, often resulting in
death. 3,4 We report a 15-year-old boy with acute
Correspondence: Dr Tanil Kendirli, 28. Sok. 31/9, Kazim Orbay, Mah.,
Akdere, 06100 Mamak, Ankara, Turkey.
Tel.: +90 312 3675058. Fax: +90 312 3620581.
E-mail: tanilkendirli@hotmail.com
Accepted for publication 22 December 2005
lymphoblastic leukaemia (ALL), whose deep-seated
infection because of fluconazole-resistant T. mucoides
was successfully treated with lipid complex amphotericin
B plus 5-fluorocytosine.
Case report
The patient was a 15-year-old boy with ALL. He had
been given delayed intensification chemotherapy
(L-asparaginase, vincristine, idarubicine, dexamethasone
and cyclophosfamide) 2 weeks previously. While
he was in a good condition, a large thrombus
(25 · 15 mm in size) was detected at the end of his
double-lumen catheter. Because the thrombus did not
dissolve with thrombolytic therapy, he had surgery.
After the operation, he had a prolonged unconsciousness,
which was possibly related to hypoxia because of
the obstruction of his endotracheal tube owing to
secretion, which has resolved within seconds with the
change of the tube. Two days later, he was admitted to
our paediatric intensive care unit (PICU) for recurrent
seizures, unconsciousness, respiratory failure and fever.
His pathological signs in the physical examination were
a temperature of 39.2 °C, left hemiplegia, absence of
deep tendon reflexes and bilateral Babinski’s sign.
Laboratory investigation revealed a haemoglobin of
10.5 g dl )1 , a white blood cell count of 3200 ll )1 [88%
polymorphonuclear leucocytes (total granulocyte count:
Ó 2006 The Authors
Journal Compilation Ó 2006 Blackwell Publishing Ltd • Mycoses, 49, 251–253 251

T. Kendirli et al.
1100 ll )1 ), 12% lymphocytes], a platelet count of
255 000 ll )1 , an erythrocyte sedimentation rate
of 67 mm h )1 and a C-reactive protein concentration
of 9.7 mg dl )1 . Urinalysis, blood biochemistries, chest
X-ray and echocardiography were normal.
Mechanical ventilation was started. His recurrent
seizures were taken under control with diazepam,
phenytoin and midazolam infusion therapy. Meropenem
was initiated for suspected sepsis. After mechanical
ventilation was discontinued on the second day of PICU
admission, cranial magnetic resonance imaging
revealed diffuse ischaemic areas.
The patient’s fever persisted. Cracking rales were
detected on the third day of meropenem therapy. Chest
X-ray revealed diffuse infiltration in the right lung
(Fig. 1) and right pleural effusion was demonstrated
with computed tomography (CT). Despite the addition of
vancomycin, his pneumonia deteriorated and he had to
be intubated again on the sixth day of his admission.
Hypotension, oliguria and cardiac tamponade developed
rapidly. Pericardial effusion showing transudate characteristics
was drained by tube pericardiocentesis;
however, Gram stain and cultures were unrevealing.
Streptokinase was instilled three times into pericardial
space for fibrinoid adhesions. The pericardial fluid
persisted for a 10-day period, at the end of which the
drainage tube was pulled out.
Because of the prolonged fever, fluconazole
(10 mg kg )1 day )1 ) was initiated on the fifth day of
hospitalisation. No microorganisms were detected in
tracheal aspirate cultures. Two of three blood cultures
were positive for T. mucoides. All isolates were identified
by conventional methods including germ tube formation,
morphology on cornmeal Tween-80 agar and Staib agar,
Figure 1 The infiltration at right-low lobe lung on his chest X-ray.
252
Figure 2 The cavitation on right-low lobe lung on thorax
computed tomography.
urease test and biochemical profile using the API 20C
AUX and ID 32C system (Bio Merieux, Lyon, France). We
determined antifungal susceptibility to itraconazole,
fluconazole, 5-fluorocytosine and amphotericin B by
ATB FUNGUS 2 (Bio Merieux). Minimal inhibitory
concentrations of 5-fluorocytosine and amphotericin B
were 1 and 2 mg l )1 respectively. However, this strain
had a very high minimum inhibitory concentration
(MIC) values for fluconazole (64 mg l )1 ) and itraconazole
(>4 mg l )1 ). Fluconazole treatment was discontinued
and lipid complex amphotericin B (5 mg kg)1 day )1 )
plus 5-fluorocytosine (100 mg kg )1 day )1 ) were initiated.
The patient’s temperature returned to normal on
the fifth day of the new antifungal drug regimen.
Meropenem and vancomycin were discontinued on their
14th day. The pneumonia gradually resolved and the
combination antifungal chemotherapy was continued
for 8 weeks. The patient’s pulmonary findings gradually
improved within 10 days. His fever was taken under
control in 5 days and he was extubated at 11th day of his
second intubation. Repeat thorax CT revealed a cavity in
the previously infiltrated area (Fig. 2). The patient was
discharged from the PICU on the 32nd day of his
admission. In the follow-up visit 4 months later, his
neurological examination was completely normal.
Discussion
Infections in immunocompromised children can result
from bacteria, fungi, viruses, or protozoa; but most
Ó 2006 The Authors
Journal Compilation Ó 2006 Blackwell Publishing Ltd • Mycoses, 49, 251–253

significant infections are caused by the host’s endogenous
bacterial flora. The most common fungal infections
in children with cancer are caused by Candida
species. The fungal pathogens of great concern in the
patient with neutropenia include Aspergillus, Fusarium,
Mucor, Pseudallescheria and Trichosporon species, as these
organisms cause rapidly progressive, extensively
destructive infections. 1,3 Our patient had various features
(haematological malignancy, chemotherapy, mild
neutropenia and open heart operation) that predispose
him to an opportunistic infection caused by a fungus,
such as T. mucoides. His steroid treatment ended
1 month before the onset of T. mucoides infection, and
also dexametasone (8 mg day )1 , for 3 weeks) was given
to him. The duration and nadir of his neutropenia were
5 days and 1100 ll )1 respectively.
Disseminated infection caused by Trichosporon species
is one of the emerging mycoses in neutropenic patients,
particularly when they are treated for haematological
malignancy with cytotoxic and immunosuppressive
chemotherapy. 3 Disseminated trichosporonosis can be
diagnosed with mycological, histopathological or serodiagnostic
tests. However, as Trichosporon species frequently
colonise the oral cavity, digestive tract, urinary
tract or the skin; the detection of Trichosporon species in
sputum or faeces is unreliable. Nonetheless, when a
Trichosporon species is detected in an abscess, in pleural
effusion or in normally sterile body fluids such as blood
and spinal fluid, this finding is clinically significant. 3–5
Our patient had clinical sepsis and T. mucoides was
isolated in blood. Pneumonia and pericarditis also
developed, but we could not demonstrate T. mucoides
in pericardial fluid or endotracheal aspirate specimens;
for this reason, pneumonia and pericarditis may be due
to microorganism(s) other than T. mucoides. In addition,
pericarditis might stem from immunological processes
such as postpericardiotomy syndrome.
Optimal therapy for serious Trichosporon infection
remains controversial. The outcome of the disease often
depends on the extent of the infection and the immune
status of the host. Many patients with profound
neutropenia or endocarditis do not respond to any form
of therapy. Most patients with disseminated Trichosporon
infection have received amphotericin B, sometimes in
combination with 5-fluorocytosine. This combination
appears to have limited activity against Trichosporon
species. There are very limited clinical data regarding
the utility of the lipid formulations of amphotericin B.
Conversely, there is growing experience that supports
azole therapy in Trichosporon infections. The most
commonly used fluconazole dosage used was
400 mg day )1 (range: 100–400 mg) for 2–26 weeks.
Mouse models from some clinical reports supported the
superiority of fluconazole over amphotericin B for
treatment of deep-seated Trichosporon infections. 2 At
the beginning, we initiated fluconazole for suspected
fungal infection; but the T. mucoides isolate was resistant
to fluconazole and itraconazole. Finally, we had to
change the antifungal chemotherapy to amphotericin B
and 5-fluorocytosine. Although the optimal duration is
controversial, we have obtained excellent clinical
response to seven weeks of 5-fluorocytosine plus amphotericin
B combination.
In conclusion, T. mucoides must be considered as an
etiological agent for sepsis and pneumonia in immunocompromised
children. Amphotericin B in combination
with 5-fluorocytosine may be a suitable treatment for
severe fungal infections; but antifungal susceptibility
should be performed for optimal therapy.
References
Successful treatment of T. mucoides
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Ó 2006 The Authors
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