Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Elinav, H. Articles by Korem, M. Search for Related Content PubMed PubMed Citation Articles by Elinav, H. Articles by Korem, M.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, April 2009, p. 1259-1263, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.01874-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CASE REPORT

Invasive Scytalidium dimidiatum Infection in an Immunocompetent Adult

Hila Elinav,¹ Uzi Izhar,² Shmuel Benenson,^1* Dan Admon,³ Carlos Hidalgo-Grass,¹ Itzhack Polacheck,¹ and Maya Korem¹

Department of Clinical Microbiology and Infectious Diseases,¹ Department of Cardiothoracic Surgery,² Department of Cardiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel³

Received 28 September 2008/ Returned for modification 15 January 2009/ Accepted 27 January 2009

Top ABSTRACT CASE REPORT ADDENDUM REFERENCES

 
Scytalidium dimidiatum, a dematiaceous fungus, has been well established as an agent of dermatomycosis. There are few reports of invasive infection caused by S. dimidiatum; most infections occurred in immunocompromised hosts. We present an immunocompetent patient with pleural S. dimidiatum infection and review nine other published cases of invasive S. dimidiatum infections.

Top ABSTRACT CASE REPORT ADDENDUM REFERENCES

 
A 56-year-old male was admitted for evaluation after a few months of progressive dyspnea, fever, night sweats, and loss of weight. His past medical history was significant for rheumatic heart disease, which had necessitated mitral valve commissurotomy 20 years prior to his admission. As a consequence, he suffered from moderate mitral and tricuspid regurgitation and moderate right heart failure, manifesting as chronic pleural effusion. He was treated with 40 mg/day furosemide and warfarin due to chronic atrial fibrillation. The last thoracentesis, performed 3 years earlier, had yielded a bloody exudate, but no pathogen was isolated.

On admission the patient appeared cachectic, had mild dyspnea, and was afebrile. The jugular veins were maximally distended. Chest examination revealed dullness to percussion and reduced breath sounds over the right lung base, and a systolic heart murmur was heard at the apex, compatible with mitral regurgitation. Hepatosplenomegaly and moderate peripheral edema were noted as well.

Significant laboratory findings were as follows: leukocyte count, 5,600 cells/µl with 61% neutrophils; hemoglobin level, 11.7 g/dl; platelet count, 164,000 platelets/µl; serum creatinine level, 111 µmol/liter; international normalized ratio, 2.41; lactate dehydrogenase, 751 IU/liter; -glutamyl transpeptidase, 133 IU/liter; alkaline phosphatase, 257 IU/liter. Chest computed tomography revealed a large loculated pleural effusion on the right with pleural thickening and total passive collapse of the right middle and lower lobes. Numerous enlarged mediastinal lymph nodes, up to 1.5 cm, were noted. Echocardiography showed enlargement of the right atrium and ventricle, in addition to mitral valve stenosis and regurgitation and moderate pulmonary hypertension.

A diagnostic thoracentesis revealed bloody exudative fluid with hemoglobin of 4.3 g/dl and white blood cell count of 2,600 cells/µl with 66% neutrophils. The lactate dehydrogenase level was 22,600 IU/liter. Septate hyphae were detected by calcofluor staining (Fig. 1A). Culture on blood agar plates yielded a white hairy mold (Fig. 1B), which progressed into a grayish black fungus (Fig. 1C). MICs were determined by Etest (AB Biodisk, Solna, Sweden). The mold was found to be susceptible to amphotericin B and voriconazole (MICs, 0.032 mg/liter) and to posaconazole (MIC, 0.75 mg/liter) but resistant to fluconazole (MIC, >256 mg/liter) and itraconazole and caspofungin (MICs, >32 mg/liter).

View larger version (168K): [in this window] [in a new window]

FIG. 1. (A) Calcofluor staining of the pleural effusion, demonstrating septate hyphae. (B) Culture on blood agar, demonstrating young white mold. (C) Culture on Sabouraud dextrose agar, demonstrating mature effuse hairy colonies, dark gray to blackish brown. (D) Microscopic examination demonstrating septate hyphae with constrictions at their prominent thick septations, giving the appearance of pseudohyphae.

The patient was treated for 2 weeks with intravenous voriconazole at 4 mg/kg of body weight every 12 h with no clinical or radiological improvement, and an exploratory right thoracotomy was performed. Necrotic tissue covering both pleural surfaces and widespread fibrosis over the atelectatic right middle and lower lobes and over the entire mediastinum were seen. Extensive debridement and irrigation of the pleural space were performed, resulting in partial expansion of the right upper and lower lobes. Cultures taken during the procedure again yielded S. dimidiatum. The patient's clinical condition gradually improved, and he was discharged 24 days after the surgery with a recommendation for continuance of the voriconazole treatment.

A month later, the patient was readmitted for dyspnea and recurrence of pleural effusion. Although septate hyphae were evident upon calcofluor staining of the pleural fluid, no mold growth was detected. The serum and pleural fluid voriconazole levels were within the therapeutic range, 1.45 mg/liter and 1.51 mg/liter, respectively (therapeutic range, 1 to 5 mg/liter [17]). Daily irrigation with amphotericin B (30 mg/day) injected through a pleural catheter was added to the treatment for 3 weeks and resulted in containment of the pleural effusion and clinical improvement. Six months later, with the patient still on voriconazole, the pleural effusion recurred.

Morphological and molecular identification. Culture on Sabouraud dextrose agar revealed effuse hairy colonies, dark gray to blackish brown, with a deep ochraceous colony reverse. Microscopic examination demonstrated septate hyphae that were constricted at their prominent thick septations, giving the appearance of pseudohyphae (Fig. 1D). Chains of arthroconidia with brown walls were produced in abundance on the aerial mycelium; many had two cells separated by a thick septum. Smooth- and thick-walled pycnidia formed after 2 weeks, showing typical pycnidioconidia with two septate conidia and a darkened central cell upon dissection. The morphological features were compatible with the diagnosis of S. dimidiatum, also known as Fusicoccum dimidiatum (8); the organism in its pycnidial state is referred to as Nattrassia mangiferae. For molecular identification, two analyses were carried out: analyses of 28S ribosomal DNA and the intergenic transcribed spacer. The sequence obtained by amplification and bidirectional sequencing of the 28S ribosomal DNA (region D1/D2) using primers NL1 and NL4 (4) was compared with those in the GenBank DNA database (BLAST). The results gave 100% query coverage and 100% identity with Scytalidium hyalinum strain ATCC 38906 and 98% query coverage and 99% identity with F. dimidiatum (synonymous with S. dimidiatum) strain CBS 312.90. Alignment of the intergenic transcribed spacer region, amplified with the primer pair LR1 and SR6R (23), resulted in 100% identity with S. hyalinum strain ATCC 38906 as well as with F. dimidiatum isolate CBS 251.49. S. hyalinum has been reported as a melanin-deficient cultural mutant of S. dimidiatum (19). Consequently the molecular methods based on ribosomal sequence cannot distinguish between these species, and the only difference is based upon the pigment production.

The patient underwent a comprehensive investigation for immunodeficiency. Human immunodeficiency virus and nitroblue tetrazolium tests were negative, and a total body computed tomography scan failed to find any underlying malignancy. As free light chains were detected in the urine, bone marrow biopsy and rectal and abdominal fat biopsies were performed, ruling out multiple myeloma or amyloidosis. The blood immunoglobulin G() to immunoglogulin G() free light chain ratio was 1.5, compatible with polyclonal gammopathy, indicating an infectious origin.

The dematiaceous (black) fungi are a large and heterogeneous group of molds that cause mostly cutaneous, subcutaneous, and corneal infections (2, 7, 9). These organisms are widespread in the environment, found in soil, wood, and decomposing plant debris, and human infection occurs mainly after traumatic implantation (8, 13). S. dimidiatum, one of the human pathogens in this group, was proven to be a major pathogen of onychomycosis and tinea pedis, causing 34.6% and 46% of cases, respectively, in a large study (22). S. dimidiatum is distinguished from dermatophytes by its characteristic sinuous, irregular hyphal appearance on direct microscopy of cutaneous specimens, its fast-growing colonies, and its sensitivity to cycloheximide (21).

A search of the English language literature up until 2008 produced only nine additional cases of invasive S. dimidiatum infection (cases of cutaneous or subcutaneous onychomycosis and keratitis were excluded), mostly in immunosuppressed patients (1, 3, 6, 10, 11, 15, 20, 21, 24) (Table 1). The underlying conditions reported, similar to those of invasive mucormycosis, were diabetes mellitus, cirrhosis, trauma, immunosuppressive therapy and chemotherapy, and transplantation. No predisposing immune deficiency was reported in only two cases (1, 15), one of them occurring after traumatic implantation (1). Variable clinical forms, including central nervous system abscess, endophthalmitis, sinusitis, osteomyelitis, and fungemia, have been described. Five out of 10 patients died (50%), and one patient that suffered from endophthalmitis was cured only after enucleation.

View this table: [in this window] [in a new window]

TABLE 1. Case reports of patients with invasive Scytalidium dimidiatum infection

Invasive mold infection is often difficult to eradicate by antifungal agents alone and usually necessitates surgical debridement. In the present case, the S. dimidiatum was isolated during the operation after 2 weeks of intravenous voriconazole treatment. Assessment of in vitro activities of various antifungal agents has demonstrated that amphotericin B and voriconazole exhibit the lowest MICs for Scytalidium spp. (14), though amphotericin B alone was found ineffective in treating cerebral infection in one case (10). It is thought that melanization in S. dimidiatum may play a role in drug resistance (16); however, it appears that the white and black isolates of Scytalidium spp. are equally resistant to antifungals (18).

Fungal thoracic empyema, which usually affects hospitalized patients, most often in intensive-care units, is associated with high morbidity and mortality rates, and its incidence has increased in recent years (12). In this retrospective analysis from Taiwan, overall mortality was estimated at 73%. Repeated thoracentesis was found to be among the major causes of fungal empyema, suggesting direct inoculation during the procedure. Those patients treated with systemic antifungal agents and surgery had a higher survival rate. In the present case of invasive pleural S. dimidiatum infection, the port of entry of the mold into the pleural space is unknown. The previous thoracentesis was performed 3 years prior to admission, the patient had no onychomycosis, and no history of trauma was reported. Although the route of invasion to the pleural space is unknown, the chronicity of the disease, as evidenced by hepatosplenomegaly and polyclonal gammopathy, suggests that it was introduced to the pleural space during the thoracentesis of 3 years previously. It is possible that the chronic pleural effusion and the presence of blood in the pleural space encouraged fungal growth and invasiveness.

Despite extensive debridement and irrigation of the pleural space and prolonged systemic antifungal therapy, local symptomatic disease recurred a month later. Reoperating was not an option due to the patient's poor general condition, and an alternative treatment was required. Intrapleural amphotericin B injection via pleural catheter was added to the treatment based upon a recent publication regarding the use of indwelling pleural catheters for chronic pleural infection (5). Clinical laboratory and radiographic studies performed 6 months later suggested stabilization of the patient's pleural disease, with marked diminution of the fluid and absence of S. dimidiatum.

This case of invasive S. dimidiatum infection is unique in the organ involved, the chronicity of the infection, and the absence of immunodeficiency. Along with the reviewed cases, it emphasizes the rarity of this entity and its relatively poor prognosis. In addition to appropriate antifungal therapy, it would be prudent to consider surgical intervention early in the course of the disease in order to improve outcome.

Nucleotide sequence accession number. The nucleotide sequence of the case isolate has been submitted to the GenBank under accession no. FJ648577.

Top ABSTRACT CASE REPORT ADDENDUM REFERENCES

 
Since this paper was accepted for publication, we have been notified by GenBank that the organism we deposited as Scytalidium dimidiatum (accession no. FJ648577) will appear in the database as Neoscytalidium dimidiatum according to its recently revised taxonomic status (see Index Fungorum, available at http://www.indexfungorum.org/Names/NamesRecord.asp?RecordID=500869, and Mycobank, at http://www.mycobank.org/MycoTaxo.aspx?Link=T&Rec=500869, accessed on 22 February 2009).

 
There are no potential conflicts of interest.

No financial support was obtained.

 
* Corresponding author. Mailing address: Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120, Israel. Phone: 972-2-6776543. Fax: 972-2-6419545. E-mail: Benenson{at}Hadassah.org.il

Published ahead of print on 4 February 2009.

Top ABSTRACT CASE REPORT ADDENDUM REFERENCES

 

1
1. al-Rajhi, A. A., A. H. Awad, S. S. al-Hedaithy, R. K. Forster, and K. C. Caldwell. 1993. Scytalidium dimidiatum fungal endophthalmitis. Br. J. Ophthalmol. 77:388-390.[Free Full Text]
2
2. Alvarez, M. I., L. A. Gonzalez, and L. A. Castro. 2004. Onychomycosis in Cali, Colombia. Mycopathologia 158:181-186.[CrossRef][Medline]
3
3. Benne, C. A., C. Neeleman, M. Bruin, G. S. de Hoog, and A. Fleer. 1993. Disseminating infection with Scytalidium dimidiatum in a granulocytopenic child. Eur. J. Clin. Microbiol. Infect. Dis. 12:118-121.[CrossRef][Medline]
4
4. Chen, Y. C., J. D. Eisner, M. M. Kattar, S. L. Rassoulian-Barrett, K. Lafe, U. Bui, A. P. Limaye, and B. T. Cookson. 2001. Polymorphic internal transcribed spacer region 1 DNA sequences identify medically important yeasts. J. Clin. Microbiol. 39:4042-4051.[Abstract/Free Full Text]
5
5. Davies, H. E., N. M. Rahman, R. J. Parker, and R. J. Davies. 2008. Use of indwelling pleural catheters for chronic pleural infection. Chest 133:546-549.[CrossRef][Medline]
6
6. Dunn, J. J., M. J. Wolfe, J. Trachtenberg, J. D. Kriesel, R. R. Orlandi, and K. C. Carroll. 2003. Invasive fungal sinusitis caused by Scytalidium dimidiatum in a lung transplant recipient. J. Clin. Microbiol. 41:5817-5819.[Abstract/Free Full Text]
7
7. Elewski, B. E. 1996. Onychomycosis caused by Scytalidium dimidiatum. J. Am. Acad. Dermatol. 35:336-338.[CrossRef][Medline]
8
8. Farr, D. F., M. Elliott, A. Y. Rossman, and R. L. Edmonds. 2005. Fusicoccum arbuti sp. nov. causing cankers on Pacific madrone in western North America with notes on Fusicoccum dimidiatum, the correct name for Scytalidium dimidiatum and Nattrassia mangiferae. Mycologia 97:730-741.[Abstract/Free Full Text]
9
9. Gentles, J. C., and E. G. Evans. 1970. Infection of the feet and nails with Hendersonula toruloidea. Sabouraudia 8:72-75.[Medline]
10
10. Geramishoar, M., K. Zomorodian, F. Zaini, F. Saadat, B. Tarazooie, M. Norouzi, and S. Rezaie. 2004. First case of cerebral phaeohyphomycosis caused by Nattrassia mangiferae in Iran. Jpn. J. Infect. Dis. 57:285-286.[Medline]
11
11. Gumbo, T., N. Mkanganwi, V. J. Robertson, and P. Masvaire. 2002. Case report. Nattrassia mangiferae endophthalmitis. Mycoses 45:118-119.[CrossRef][Medline]
12
12. Ko, S. C., K. Y. Chen, P. R. Hsueh, K. T. Luh, and P. C. Yang. 2000. Fungal empyema thoracis: an emerging clinical entity. Chest 117:1672-1678.[CrossRef][Medline]
13
13. Lacaz, C. S., A. D. Pereira, E. M. Heins-Vaccari, L. C. Cuce, C. Benatti, R. S. Nunes, N. T. de Melo, R. S. de Freitas-Leite, and G. L. Hernandez-Arriagada. 1999. Onychomycosis caused by Scytalidium dimidiatum. Report of two cases. Review of the taxonomy of the synanamorph and anamorph forms of this coelomycete. Rev. Inst. Med. Trop. Sao Paulo 41:319-323.[Medline]
14
14. Lacroix, C., and M. F. de Chauvin. 2008. In vitro activity of amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and terbinafine against Scytalidium dimidiatum and Scytalidium hyalinum clinical isolates. J. Antimicrob. Chemother. 61:835-837.[Abstract/Free Full Text]
15
15. Mani, R. S., Y. T. Chickabasaviah, S. Nagarathna, A. Chandramuki, M. R. Shivprakash, J. Vijayan, D. K. Prashantha, P. S. Vasudevan, A. Natarajan, and J. Kovoor. 2008. Cerebral phaeohyphomycosis caused by Scytalidium dimidiatum: a case report from India. Med. Mycol. 46:705-711.[CrossRef][Medline]
16
16. Morris-Jones, R., S. Youngchim, J. M. Hextall, B. L. Gomez, S. D. Morris-Jones, R. J. Hay, A. Casadevall, J. D. Nosanchuk, and A. J. Hamilton. 2004. Scytalidium dimidiatum causing recalcitrant subcutaneous lesions produces melanin. J. Clin. Microbiol. 42:3789-3794.[Abstract/Free Full Text]
17
17. Pascual, A., T. Calandra, S. Bolay, T. Buclin, J. Bille, and O. Marchetti. 2008. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin. Infect. Dis. 46:201-211.[CrossRef][Medline]
18
18. Polak, A., and D. M. Dixon. 1989. Loss of melanin in Wangiella dermatitidis does not result in greater susceptibility to antifungal agents. Antimicrob. Agents Chemother. 33:1639-1640.[Abstract/Free Full Text]
19
19. Roeijmans, H. J., G. S. De Hoog, C. S. Tan, and M. J. Figge. 1997. Molecular taxonomy and GC/MS of metabolites of Scytalidium hyalinum and Nattrassia mangiferae (Hendersonula toruloidea). J. Med. Vet. Mycol. 35:181-188.[Medline]
20
20. Sadeghi Tari, A., M. Mardani, M. Rahnavardi, F. Asadi Amoli, and Z. Abedinifar. 2005. Post-traumatic fatal Nattrassia mangiferae orbital infection. Int. Ophthalmol. 26:247-250.[CrossRef][Medline]
21
21. Tan, D. H., L. Sigler, C. F. Gibas, and I. W. Fong. 2008. Disseminated fungal infection in a renal transplant recipient involving Macrophomina phaseolina and Scytalidium dimidiatum: case report and review of taxonomic changes among medically important members of the Botryosphaeriaceae. Med. Mycol. 46:285-292.[CrossRef][Medline]
22
22. Ungpakorn, R. 2005. Mycoses in Thailand: current concerns. Nippon Ishinkin Gakkai Zasshi 46:81-86.[Medline]
23
23. White, T. J., T. Bruns, S. Lee, and J. Taylor. 1990. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics, p. 315-322. In M. A. Innis, D. H. Gelfand, J. J. Sninsky, and T. J. White (ed.), PCR protocols: a guide to methods and applications. Academic Press, San Diego, CA.
24
24. Willinger, B., G. Kopetzky, F. Harm, P. Apfalter, A. Makristathis, A. Berer, A. Bankier, and S. Winkler. 2004. Disseminated infection with Nattrassia mangiferae in an immunosuppressed patient. J. Clin. Microbiol. 42:478-480.[Abstract/Free Full Text]

---

Journal of Clinical Microbiology, April 2009, p. 1259-1263, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.01874-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Elinav, H. Articles by Korem, M. Search for Related Content PubMed PubMed Citation Articles by Elinav, H. Articles by Korem, M.