Verruconis gallopava cardiac and endovascular infection with dissemination after renal transplantation: Case report and lessons learned☆☆☆

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Abstract

Verruconis gallopava is an uncommon cause of phaeohyphomycosis. We describe an unusual case of disseminated V. gallopava infection in a renal transplant recipient involving the endocardium but without endocarditis, associated with fungaemia and infection in the skin, oral cavity, brain and lung. The isolate was first detected from blood cultures which is rare. Surgical resection of cardiac fungal mass was not possible. The patient died despite resolution of fungaemia and combination antifungal therapy.

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Most cited references 19

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Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes, including chromoblastomycosis, mycetoma, and phaeohyphomycosis. [corrected]. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.

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Melanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H(2)O(2). Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning.

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Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These fungi rarely cause life-threatening disease. We reviewed 101 cases of culture-proven primary central nervous system phaeohyphomycosis reported in the English-language literature from 1966 to 2002. The most frequently isolated species was Cladophialophora bantiana. The next most frequent isolate was Ramichloridium mackenziei, seen exclusively in patients from the Middle East. More than one-half of the cases occurred in patients with no known underlying immunodeficiency. Mortality rates were high regardless of immune status. Therapy is not standardized, although the combination of amphotericin B, flucytosine, and itraconazole may improve survival rates. Newer azoles, such as voriconazole, also have a broad spectrum of activity against these fungi, although clinical experience is limited. Complete excision of brain lesions may provide better results than simple aspiration. An aggressive medical and surgical approach is warranted in treating these infections to optimize outcomes.

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Author and article information

Contributors

Zoe Jennings

Journal

Journal ID (nlm-ta): Med Mycol Case Rep

Journal ID (iso-abbrev): Med Mycol Case Rep

Title: Medical Mycology Case Reports

Publisher: Elsevier

ISSN (Electronic): 2211-7539

Publication date PMC-release: 13 December 2016

Publication date Collection: March 2017

Publication date (Electronic): 13 December 2016

Volume: 15

Pages: 5-8

Affiliations

[a ]Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR – Pathology West, Westmead Hospital, Sydney, Australia

[b ]Deparment of Renal Medicine, Westmead Hospital, Sydney, Australia

[c ]Centre for Transplant and Renal Research, Westmead Hospital and Sydney School of Public Health, The University of Sydney, Sydney, Australia

[d ]Marie Bashir Institute for Infectious Diseases & Biosecurity, The University of Sydney, Sydney, Australia

Author notes

[* ]Corresponding author. zoe.jennings@ 123456health.nsw.gov.au

Article

Publisher ID: S2211-7539(16)30062-8

DOI: 10.1016/j.mmcr.2016.12.006

PMC ID: 5198741

PubMed ID: 28053851

SO-VID: 7d8d4732-2460-4e3e-8242-8b1a67d78eeb

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 14 November 2016

Date revision received : 12 December 2016

Date accepted : 12 December 2016

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