Download Disseminated Trichosporonosis mucoides in a uremic patient with

Disseminated Trichosporonosis mucoides in a uremic patient with type 2 diabetes
mellitus on maintenance hemodialysis
ING-CHIN JONG1, WO-JONG HSU2 , PEIR-HAUR HUNG1,
THIH-YEN HSIAO1
,
PEI-CHUN
CHIANG1, CHIN-CHUNG TSENG3
1
Division of Nephrology, 2Division of Infectious Disease, Department of Internal Medicine, Chia-Yi
Christian Hospital, Chia-Yi, Taiwan and 3Division of Nephrology, Department of Internal Medicine,
National Cheng Kung University Hospital,
Tainan, Taiwan.
Correspondence author: Dr. Chin-chung Tseng, Division of Nephrology, Cheng Kung University Hospital,
No. 138 Shianli Road, Tainan 70428, Taiwan.
E-mail: [email protected]
Abstract
Invasive Trichosporon mucoides infections are very rare in uremic patients. They are almost
exclusively seen in immunocompromised patients, especially in the setting of neutropenic patients with
hematologic malignancies. We report the case of a 62-year-old uremic woman, without neutropenic and
on maintenance hemodialysis for four years, who developed nosocomial disseminated Trichosporonosis
mucoides with the probable focus of entry of infected right Hickmann catheter during a hospital
admission for shortness of breath. The blood culture yielded Trichosporon mucoides, and amphotericin-B
(0.5 mg/kg/day) was given with a successfully completed therapy in addition to the immediate removal of
the Hickmann catheter.
However, sepsis recurred and pus culture from the stump of the left knee yielded
T. mucoides. In addition to increasing the dosage of amphotericin B to 1 mg/kg/day, oral variconazole
300 mg every 12h were added, too. Stump revision was also performed and her condition improved
thereafter. Disseminated trichosporonosis should be considered in the differential diagnosis of elderly
uremic patients with diabetes, severe peripheral arterial occlusive disease and intravenous catheter ,
when sepsis does not improve after prolonged treatment with broad-spectrum parenteral antibiotics.
Removal of intravenous catheter, management for the infectious wound and aggressive anti-fungal agents
are necessary for a successful Trichosporon mucoides treatment.
Key words
: diabetes mellitus type2 ,hemodialysis, Trichosporon mucoides,
uremia
INTRODUCTION
Invasive Trichosporon mucoides infections are almost exclusively seen in immunocompromised
patients. The majority of trichosporonosis cases are seen in neutropenic individuals, usually in the
setting of a hematologic malignancy.1 They are very rare in uremic patients. Other reported risk factors
include AIDS, extensive burns, intravenous catheters,2 corticosteroid treatment, and heart valve surgery.
And several cases of fungal peritonitis in patients on continuous ambulatory peritoneal dialysis had
been reported.
We report a 62-year-old, non-neutropenic woman with a history of type 2 diabetic nephropathy in
end-stage renal disease on maintenance hemodialysis for four years, who developed a disseminated
Trichosporonosis mucoides infection during a hospital admission for the chief complaint of shortness
of breath. We believe that this is the first such case of nosocomial T. mucoides infection in a patient on
maintenance hemodialysis reported in the clinical literature.
Case report
A 62-year-old woman with type 2 diabetes mellitus and diabetic nephropathy, had been on
chronic maintenance hemodialysis since 10 October 2002. During this course, she was admitted
several times to our hospital. The most recent four admissions were for osteomyelitis in the right
talus and necrotizing fasciitis of the right leg, and peripheral arterial occlusive disease, resulting in
amputation above the knee of the left leg.
Reportedly, she had general weakness and periodic consciousness disturbances for 2 days prior
being brought to the emergency department on 5 April 2006. Physical examination upon arrival
revealed a 62-year-old woman with drowsy consciousness. Her blood pressure was 127/53 mmHg
with body temperature 36°C, pulse rate 64 beats/min, and respiration rate 25 breaths/min. Chest
auscultation revealed crackles over both lung fields. A 5 x 4 x 3-cm deep, dirty, and poorly healing
wound in the inner aspect of her right thigh and a 5 x 4 x 0.5-cm ulcerated wound in the posterior
aspect of her right lower leg were noted
(Fig. 1); her left leg had been amputated above the knee.
The contributory laboratory data showed white blood cells of 14,000/μl, with 68% neutrophils. The
initial chest X-ray showed cardiomegaly, with mild bilateral infiltrations. She was admitted to the
intensive care unit under the impression of sepsis, with the suspected focus at the deep, dirty wound
in the right thigh or pneumonia.
Empirical antibiotics were given with piperacillin 4.0 g, tazobactam 0.5 g every 12 h, and gentamicin
40 mg following hemodialysis three times weekly. The patient’s fever rose to 38°C 2 days after
admission; teicoplanin 200 mg every 3 days was added to cover the probability of
methicillin-resistant Staphylcoccus aureus infection in the wound. The blood and sputum cultures
yielded nothing peculiar, but the pus cultures on 25 April 2006 from the exit site of the right
Hickmann catheter and the wound in the right lower extremity yielded yeast-like organism. So that
the Hickmann catheter was removed promptly and intravenous fluconazole 100 mg daily was given.
However, her fever did not subside, and repeated blood cultures on 28 April 2006 yielded T.
mucoides. Amphotericin B (0.5 mg/kg/day) was given instead of fluconazole, according to the
sensitivity test of T. mucoides. Her conditions changed dramatically following amphotericin B
treatment. She was discharged on 10 June 2006, and amphotericin B 50 mg was administered thrice
weekly during maintenance hemodialysis.
Unfortunately, she was admitted again on 14 June 2006, with the chief complaint of shortness of
breath. In addition to increasing the amphotericin B dosage to 1 mg/kg/day, piperacillin 4.0 g and
tazobactam 0.5 g every 12 h were added due to a fetid odor and discharge from the stump of the left
knee, with the stump culture on 16 June 2006 yielded T. mucoides mixed with bacterial floras,
indicating a recurrent infection. In the meanwhile, oral variconazole 300 mg every 12 h were given.
Blood culture and fungus culture on 14 June 2006 showed no findings.
Stump revision was
performed on 21 June 2006. And her condition improved dramatically thereafter.
DISCUSSION
The genus Trichosporon includes approximately 30 species, at least six of which (T. asahii, T.
mucoides, T. inkin, T. ovoides, T. cutaneum, and T. asteroides) are known as Trichosporon beigelii,3 and
are associated with human infections (trichosporonosis).3 These fungi are found in nature,
predominately in soil. Mucosal surfaces, skin, throat, stools, the lower urinary tract, sputum, nails and
hair are reported as sites of colonization with Trichosporon beigelii.
In clinical specimens, a
yeast-like organism that is urease positive and forms arthroconidia can be presumptively identified as
Trichosporon beigelii. The specimen from our patient was identified as T. mucoides according to the
API 20C AUX system (bioMerievx, Basingstoke, UK).
Most invasive T. mucoides infections probably start with colonization of the mucosal surfaces,
with a break in the integrity of the surface subsequently seeding the bloodstream. Antibiotics probably
increase the incidence and extent of colonization and play a role in increasing the risk of human
infections. For our patient without neutropenia, the predisposing risk factors included prolonged
antibiotic treatments during several repeated admissions, type 2 diabetes, and the right side intravenous
Hickman-catheter. The specific clinical picture of this patient was one of severe peripheral arterial
occlusive disease, with multiple gangrenous areas in the lower extremities. The portal of entry for T.
mucoides could have been from the insertion site of the right side Hickman-catheter or from the wound
in the right lower extremity; pus was noted at the wound and around the catheter. Even though the pus
cultures from these wounds grew what was identified initially as C. albicans, it was probably T.
mucoides. The patient’s fever did not subside after intravenous fluconazole treatment, which was
effective in controlling the systemic C. albicans infection. T. mucoides was likely to be confused with
C. albicans because of their close resemblance on histological examination.4
However, mixed
infection could not be excluded absolutely without doubt. The common presentations described in the
literature comprise pneumonia, hypersensitivity pneumonitis, peritonitis, skin lesions, chronic urinary
tract infection, brain abscess, endophthalmitis, endocarditis, or septic shock. The patient’s presenting
symptoms were sepsis, and disturbed consciousness.
According to sensitivity testing, the treatment of choice was amphotericin-B, but the optimal
antifungal agents and duration of therapy have not been established. Variconazole, a new
extended-spectrum triazole, posaconazole, and ravuconazole reportedly have good activity against
Trichosporon species in vitro.5 Thus, we added oral variconazole 300 mg every 12 h and increased the
amphotericin B dosage to 1 mg/kg/day due to progression of disseminated T. mucoides. Clinical
experience from the use of antifungal agents for the treatment of trichosporonosis suggests that the
drug used for treatment is probably not as important as the status of the underlying disease of the host.
The prognosis is poor and most often fatal in patients in poor physical and immune condition, despite
treatment. So, a stump revision was also performed. As a consequence, her condition dramatically
improved thereafter.
CONCLUSION
In conclusion, though invasive T. mucoides infections are very rare in uremic non-neutropenic
patients, they should be considered in the differential diagnosis of elderly uremic non-neutropenic
patients with diabetes, severe peripheral arterial occlusive disease, and indwelling intravenous catheters
when sepsis does not improve after prolonged treatment with broad-spectrum parenteral antibiotics.
Removal of the intravenous catheter, stump revision to eradicate the infection focus and managements
for the infectious wound, in addition to aggressive anti-fungal agents, are necessary for a successful T.
mucoides treatment.
Figure legends
Fig. 1- Photograph taken on the patient’s first admission (used with permission of patient and
family) showed large, ulcerated, poorly healing wounds scattered over the inner aspect of the right
thigh and the posterior aspect of the right lower leg.
ACKNOWLEDGEMENTS
Support: None.
Financial Disclosure: None.
REFERENCES
1. Girmenia C, Pagano L, Martino B, et al. Invasive infections caused by Trichosporon species and
Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study
from Italy and review of the literature. J Clin Microbiol
2005;43( 4 ):1818-1828.
2. Finkelstein R, Singer P, Lefler E. Catheter-related fungemia caused by Trichosporon beigelii in
non-neutropenic patients. Am J Med 1989; 86( 1 ):133.
3. Gueho E, Smith, MT, de Hoog, GS, et al. Contributions to a revision of the genus Trichosporon. Antonie
Van Leeuwenhoek 1992; 61( 4 ):289-316.
4. Mori T, Kohara T, Matsumura M, et al. A case of polymycotic septicemia caused by Trichosporon
beigelii, Candida albicans, and Candida krusei. Jpn J Med Mycol 1988; 29:120-6.
5. Falk R, Wolf DG, Shapiro M, Dolacheck I. Multidrug-resistant Trichosporon asahii isolates are
susceptible to variconazole. J Clin Microbiol 2003;41( 2 ):911-912.
Figure legends
Fig. 1- Photograph taken on the patient’s first admission (used with permission of patient and family)
showed large, ulcerated, poorly healing wounds scattered over the inner aspect of the right thigh and
the posterior aspect of the right lower leg.
探討第二型糖尿病併尿毒症
接受維持性血液透析治療患者的廣泛性
Trichosporonosis mucoides 的感染
鐘應欽*
許國忠**
洪培豪*
蕭志彥*
江培群*
曾進忠***