(Exophiala) dermatitidis - Journal of Clinical Microbiology - American

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bei Patienten mit Mukoviszidose. Mycoses 37(Suppl. 1):89–96. 2. Centers for Disease Control and Prevention. 1994. Revised classification system for human ...
JOURNAL OF CLINICAL MICROBIOLOGY, Apr. 1996, p. 1011–1013 0095-1137/96/$04.0010 Copyright q 1996, American Society for Microbiology

Vol. 34, No. 4

Catheter-Associated Fungemia Due to Wangiella (Exophiala) dermatitidis SHARON NACHMAN,1 ORAL ALPAN,1 RONALD MALOWITZ,2 3 AND ERIC D. SPITZER * Departments of Pediatrics,1 Medical Technology,2 and Pathology,3 SUNY at Stony Brook, Stony Brook, New York Received 16 August 1995/Returned for modification 19 October 1995/Accepted 13 December 1995

We describe a case of catheter-associated Wangiella (Exophiala) dermatitidis fungemia in a human immunodeficiency virus-infected child who was successfully treated with antifungal therapy and catheter removal. Catheter-associated W. dermatitidis fungemia appears to be distinct from previously described cases of disseminated infection with organ involvement. Wangiella (Exophiala) dermatitidis is a dematiaceous yeastlike mold found in the environment. It is a well-known cause of local and disseminated pheohyphomycosis but is an uncommon cause of fungemia. In this report, we describe a case of central venous catheter-associated W. dermatitidis fungemia in a human immunodeficiency virus (HIV)-infected child and review the recent literature on this type of infection. The clinical features of catheter-associated W. dermatitidis fungemia appear to be distinct from those of previously described cases of disseminated infection with deep organ involvement. A 3-year-old male with stage C-3 (2) vertically acquired HIV type 1 infection was admitted to our hospital for evaluation of fever and a positive blood culture. He had previously been hospitalized multiple times for opportunistic infections, including Pneumocystis carinii pneumonia, and was receiving a continuous zidovudine infusion through a central venous catheter because of progressive HIV-associated central nervous system disease. One month before admission, he had been treated for penicillin-resistant Streptococcus pneumoniae sepsis. Three days before admission, he was seen as an outpatient because of new onset of fever to 38.98C. Blood cultures were drawn from the central venous catheter and from a peripheral vein, and vancomycin therapy was started. Three days later, yeastlike fungi were found in one of the catheter blood cultures, and he was admitted for further evaluation. He was afebrile at the time of admission. Physical examination revealed a I/VI degree systolic ejection murmur at the left midsternal border, hepatomegaly, spastic quadriparesis, and facial diplegia, all of which were present before admission and thought to be due to his underlying HIV infection. The leukocyte count on admission was 7,600 cells per ml, with a differential of 61% neutrophils, 24% band forms and 9% lymphocytes. A recent CD41 T-cell count was 334 cells per ml. Hepatic enzyme levels were elevated (aspartate aminotransferase, 580 IU/ml; alanine aminotransferase, 102 IU/ml) but unchanged from previous values. Blood cultures were drawn from the central venous catheter and a peripheral vein. Vancomycin treatment was discontinued, and amphotericin B treatment was started. Three days later, yeastlike fungi were again recovered from the catheter and peripheral venous blood cultures. All of these isolates were later identified as W. dermatitidis (see below).

The patient was thought to have catheter-associated fungemia, and the catheter was removed (the culture of the tip was negative but was incubated for only 2 days). Clinical evaluation, including computerized tomography of the head, renal ultrasound examination, and ophthalmologic examination, did not reveal evidence of disseminated fungal infection. Repeat blood cultures collected after the initiation of amphotericin B therapy were negative. The patient was discharged from the hospital and amphotericin therapy was continued. He received a total of 27 mg of amphotericin B per kg of body weight. Three weeks later, a new central venous catheter was inserted. Two weeks later, the patient developed swelling, tenderness, and erythema at the catheter site. Although cultures were negative, amphotericin B treatment was restarted for a possible recurrence of the fungal infection. There was rapid clinical improvement, and after 1 month the antifungal agent was changed to itraconazole. The itraconazole therapy was discontinued after 5 months. A subsequent magnetic resonance image of the brain did not reveal any enhancing lesions or evidence of cerebritis. No evidence of new lesions was seen on ultrasound examination of the liver, kidneys, and spleen. No pulmonary nodules were seen on a computerized tomography scan of the lungs. The blood specimens described above were inoculated into Bactec Peds Plus/F aerobic medium (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) and incubated in a Bactec 9240 blood culture system. All but one of the positive bottles produced a positive growth index after 3 to 4 days (W. dermatitidis was recovered from one catheter blood culture that had been collected during the patient’s earlier episode of pneumococcal sepsis and was incubated for 28 days). Gram stains revealed yeastlike fungi. The positive bottles were subcultured on sheep blood agar and inhibitory mold agar and produced light gray yeastlike colonies after 48 h at 358C. Upon further incubation, the colonies turned shiny black. Slide cultures prepared on potato dextrose agar at 308C revealed long, slender conidiophores with clusters of oval conidia at the tips of the phialides and aggregates of conidia along the sides of the conidiophores (Fig. 1). The organism grew at 38 and 40 but not 428C and utilized tyrosine but not casein. On the basis of these properties, it was identified as W. dermatitidis. The identification was confirmed by the New York State Department of Health Mycology Laboratory. W. dermatitidis is a dematiaceous yeastlike fungus that has been isolated from several environmental sources. The genus Wangiella was established in 1977 to accommodate a dematia-

* Corresponding author. Mailing address: Department of Pathology, SUNY at Stony Brook, Stony Brook, NY 11794-8691. Phone: (516) 444-2382. Fax: (516) 444-3419. Electronic mail address: espitzer@path .som.sunysb.edu. 1011

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FIG. 1. Slide culture showing oval conidia and tapered conidiophores of W. dermatitidis. The stain used was lactophenol cotton blue. Magnification, 3400.

ceous mold that had phialides without collarettes. Electron microscopy studies have shown that some isolates contain a synanomorph that exhibits annelidic development typical of Exophiala spp. (6). As a result, the taxonomy of this fungus remains controversial, and some authors refer to it as E. dermatitidis. W. dermatitidis can be distinguished from morphologically similar Exophiala species on the basis of thermotolerance. Matsumoto et al. reported that 20 of 21 isolates grew at 408C (8). Previous reports have emphasized the high mortality rate associated with disseminated W. dermatitidis infections and the neurotropic behavior of this organism. Matsumoto et al. reviewed 37 cases of pheohyphomycosis caused by W. dermatitidis (7). In 20 cases, there was evidence of systemic disease, including 12 fatal disseminated infections with involvement of the skin, lymph nodes, central nervous system, and viscera; however, the authors noted a declining trend in mortality over time. Kenney et al. described a patient with chronic granulomatous disease who had a pulmonary mass containing W. dermatitidis (5). Although there was no clinical evidence of central nervous system infection, a magnetic resonance imaging scan of the brain revealed a ring-enhancing lesion. This presumptive systemic infection was successfully treated through resection of the pulmonary mass, leukocyte transfusions, and combination antifungal therapy. There have been three reports describing cases of catheterassociated W. dermatitidis fungemia without deep organ involvement. In all of the cases, W. dermatitidis was isolated from central venous catheter and peripheral venous blood cultures. Two cases involved children with acute lymphoblastic leukemia and neutropenia. In one case, the catheter was removed and the patient was treated with itraconazole for 8 weeks (4). There was no evidence of systemic disease during 6 months of followup. In the second case, the catheter was removed and the patient was treated with amphotericin B and 5-fluorocytosine for 3 weeks (1). There was no evidence of disseminated disease. The other case involved a 53-year-old woman receiving parenteral nutrition following a colectomy (9). The catheter

was removed, and she was treated with fluconazole for 4 days. She remained well during 2 years of followup. The clinical features of our case also resemble the cases of fungemia in HIV-infected children described by Walsh et al. (10). In their study, fungemia occurred only in patients with central venous catheters. Most of the infections were community acquired, and fever was the most common presenting sign. There were no complications in those patients treated with amphotericin B and catheter removal. Most of the infections were caused by Candida spp., but one case was caused by the dematiaceous mold Bipolaris spicifera. W. dermatitidis is an uncommon cause of fungemia. There were no isolates among over 6,000 fungal blood isolates recovered during a 20-year period at the Mayo Clinic (3). Nonetheless, this report and other recent reports indicate that W. dermatitidis should be added to the list of agents that cause central venous catheter-associated fungemia. Prompt intervention appears to prevent disseminated disease. We thank Thomas Walsh for useful discussions and Evelyn Rosenthal for assistance in identifying the fungal isolate.

REFERENCES 1. Blaschke-Hellmessen, R., I. Lauterbach, K. D. Paul, K. Tintelnot, and G. Weissbach. 1994. Nachweis von Exophiala dermatitidis (Kano) De Hoog 1977 bei Septika¨mie eines Kindes mit akuter lymphatischer Leuka ¨mie und bei Patienten mit Mukoviszidose. Mycoses 37(Suppl. 1):89–96. 2. Centers for Disease Control and Prevention. 1994. Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. Morbid. Mortal. Weekly Rep. 43:(RR-12):1–12. 3. Geha, D. J., and G. D. Roberts. 1994. Laboratory detection of fungemia. Clin. Lab. Med. 14:83–97. 4. Kabel, P. J., K. E. Illy, R. A. Holl, A. G. Buiting, and R. G. Wintermans. 1994. Nosocomial intravascular infection with Exophiala dermatitidis. Lancet 344: 1167–1168. 5. Kenney, R. T., K. J. Kwon-Chung, A. T. Waytes, D. A. Melnick, H. I. Pass, M. J. Merino, and J. I. Gallin. 1992. Successful treatment of systemic Exophiala dermatitidis infection in a patient with chronic granulomatous disease. Clin. Infect. Dis. 14:235–242.

VOL. 34, 1996 6. Kwon-Chung, K. J., and J. E. Bennett. 1992. Medical mycology. Lea & Febiger, Philadelphia. 7. Matsumoto, T., T. Matsuda, M. R. McGinnis, and L. Ajello. 1993. Clinical and mycological spectra of Wangiella dermatitidis infections. Mycoses 36: 145–155. 8. Matsumoto, T., A. A. Padhye, L. Ajello, and P. G. Standard. 1984. Critical review of human isolates of Wangiella dermatitidis. Mycologia 76:232–249.

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9. Simpson, A. J. H., and J. M. D. Nightingale. 1995. Intravascular line infection with Exophiala dermatitidis. Lancet 345:67. 10. Walsh, T. J., C. Gonzalez, E. Roilides, B. U. Mueller, N. Ali, L. L. Lewis, T. O. Whitcomb, D. J. Marshall, and P. A. Pizzo. 1995. Fungemia in children infected with the human immunodeficiency virus: new epidemiologic patterns, emerging pathogens, and improved outcome with antifungal therapy. Clin. Infect. Dis. 20:900–906.