Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

Abstract

e Despite increasing reports of human infection, data about the optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides, initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation (n ‫؍‬ 17), diabetes or glucose intolerance (n ‫؍‬ 10), rheumatoid arthritis or Still's disease (n ‫؍‬ 4), chronic hematological diseases (n ‫؍‬ 3), or chronic granulomatous disease (n ‫؍‬ 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n ‫؍‬ 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections (n ‫؍‬ 6). The main antifungal drugs used were azoles (n ‫؍‬ 41) and amphotericin B (n ‫؍‬ 16). Surgical excision or drainage was performed in 64% of cases (n ‫؍‬ 27). The cure rate was 67% (n ‫؍‬ 28). There were 10% cases of treatment failure or partial response (n ‫؍‬ 4), 19% relapses (n ‫؍‬ 8), and 7% losses to follow-up (n ‫؍‬ 3). The death rate was 19% (n ‫؍‬ 8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy. R eports of human diseases related to dark molds are increasing with the expanded spectrum of immunocompromised patients. Phaeohyphomycoses are a heterogenous group of cutaneous, subcutaneous, and systemic infections caused by fungi that are distributed worldwide, with melanized cell walls that develop in the host's tissue as dark-walled septate mycelial elements (1). Phaeoacremonium species, which are found in the environment in soil or in woody plants, as endophytes or as agents of plant disease, particularly in grapevines (2), are included in the phaeohyphomycosis group. Initially described in 1974 as Phialophora parasitica by Ajello et al. (3) and then transferred in 1996 to the new hyphomycete genus Phaeoacremonium by Crous et al., as Phaeoacremonium parasiticum (4), this fungus is a rare cause of human disease, occurring in both immunocompetent and immunosuppressed subjects. Reports of Phaeoacremonium infections are increasing over time, probably because laboratory confirmation of fungal pathogens has improved and because of the increase in immunocompromised conditions in the population. However, clinical and treatment data on Phaeoacremonium infection are scarce.We describe a case of a disseminated in...

In Vitro Susceptibility Profiles of Eight Antifungal Drugs against Clinical and Environmental Strains of Phaeoacremonium

“…Also, unsuccessful treatment of P. rubrigenum subcutaneous infections with itraconazole (MICs of Ͼ8 g/ml) has been on record (8). Similar to our findings, low MICs of voriconazole and posaconazole among the azoles were noted in a recent review of antifungal susceptibility data from eight Phaeoacremonium isolates by Colombier et al (3). A recent European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) joint clinical guideline for the diagnosis and management of systemic phaeohyphomycosis recommends triazoles for the treatment of infections by melanized fungi (32).…”

“…In a recent comprehensive review by Gramaje et al (2) on the nomenclature of this genus, 11 Phaeoacremonium species have been confirmed as human opportunistic pathogens causing infections in both immunocompromised and immunocompetent hosts. The most frequent species identified in human infections are P. parasiticum, P. inflatipes, and P. rubrigenum (3,4). Furthermore, since 2006 many new cases of Phaeoacremonium infections implicating other species such as P. krajdenii, P. venezuelense, P. minimum, and P. aleophilum have been described (4)(5)(6).…”

“…Furthermore, since 2006 many new cases of Phaeoacremonium infections implicating other species such as P. krajdenii, P. venezuelense, P. minimum, and P. aleophilum have been described (4)(5)(6). An excellent review of clinical cases reported worldwide due to species of Phaeoacremonium revealed that in 57% of the cases, infections were localized in skin and subcutaneous tissues (3). However, in the remaining 43% of cases, a wide spectrum of infections ranging from osteoarticular involvement, pulmonary nodules, endophthalmitis, invasive disseminated infection associated with fungemia, brain abscesses, endocarditis, and liver and spleen abscesses were observed (5)(6)(7)(8)(9)(10)(11)(12).…”

“…However, in the remaining 43% of cases, a wide spectrum of infections ranging from osteoarticular involvement, pulmonary nodules, endophthalmitis, invasive disseminated infection associated with fungemia, brain abscesses, endocarditis, and liver and spleen abscesses were observed (5)(6)(7)(8)(9)(10)(11)(12). Disseminated and severe infections were commonly associated with solid organ transplantation and other immunosuppressive conditions (3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Considering that the morphological identification of black fungi, and of Phaeoacremonium in particular, is problematic (28) and relies on sequencing of the internal transcribed space (ITS) ribosomal DNA (rDNA) region or ␤-tubulin or calmodulin genes (29)(30)(31), many cases in routine microbiology laboratories may have passed unnoticed (28).…”

Coelomycetous Fungi in the Clinical Setting: Morphological Convergence and Cryptic Diversity

“…Although Paraconiothyrium cyclothyrioides was relatively common in our studied samples, there are only two clinical reports that refer to this species. Both cases are from immunocompromised patients; in one case P. cyclothyrioides caused skin lesions of the lower extremities, and in the second case it produced a systemic coinfection together with Phaeoacremonium parasiticum (37,38). Even though Phoma sporulates easily, it is commonly misidentified as other related genera, such as Ascochyta, because the genera have similar morphologies, physiologies, and nucleotide sequences (39,40).…”