Phaeoacremonium parasiticum Infections Confirmed by β-Tubulin Sequence Analysis of Case Isolates

Abstract

Phaeoacremonium parasiticum is an agent of opportunistic phaeohyphomycosis belonging to a genus encompassing numerous recently described and soon-to-be-described, difficult-to-identify human pathogens. It appears in the literature to be an uncommon etiologic agent, yet we encountered several cases in a single year. Each presented problems in laboratory identification and case management. We present two cases of invasive disease with definite identification and susceptibility results. These cases are analyzed in relation to a brief review of previous cases known to have been caused by this species. Our first case involved a 40-year-old male cardiac transplant recipient with multiple localized skin lesions. The second featured a 31-year-old female with aplastic anemia and prolonged neutropenia who developed disseminated disease, with multiple positive blood cultures and skin lesions. Both patients died despite aggressive surgical and antifungal therapy. Fungal susceptibility testing showed that our isolates appeared to be susceptible to amphotericin B, itraconazole, voriconazole, ravuconazole, and posaconazole. Because phenotypic identification of Phaeoacremonium is notably problematic, sequence-based confirmation was performed using a recently proposed standard based on use of a segment of the 5 end of the ␤-tubulin gene. Sequences from both isolates involved in the cases were over 99% similar to the corresponding sequence of the ex-type isolate of P. parasiticum. The close DNA similarity, corroborated by relevant morphological similarities (e.g., long, thin phialides and tuberculate hyphae bearing warts up to 3 m high), confirms these two isolates as P. parasiticum.

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

“…We found one series of cases of phaeohyphomycosis (6), a series of fungal lung infections in patients with chronic granulomatous disease (7), and a series of invasive fungal infections in lung transplant patients (8), as well as four brief literature reviews, each reporting a few cases of Phaeoacremonium infections (9)(10)(11)(12) , an initial cutaneous trauma was reported, usually several months or years earlier. Potential environmental exposure because of working or leisure activities was noted in 8 cases, including for our patient.…”

“…Potential environmental exposure because of working or leisure activities was noted in 8 cases, including for our patient. In some cases, no trauma was noted (9).…”

“…Identification of Phaeoacremonium species is difficult because the cultural and microscopic distinguishing characteristics are relatively minor (2). Also, some of the most common species causing human disease were not described before 2005 (or taxonomically redressed since then) and therefore were probably misidentified in earlier publications (9). Molecular methods have been developed to confirm species identifications (17); these are best supported by phylogenetic analyses of actin, ␤-tubulin, and calmodulin gene sequences.…”

“…The reported systemic antifungal agents used to treat Phaeoacremonium phaeohyphomycosis included amphotericin B in deoxycholate or lipid form, azoles (voriconazole, itraconazole, fluconazole, and posaconazole), terbinafine, and caspofungin, but the optimal antifungal treatment for invasive disease is uncertain. In vitro, Phaeoacremonium is usually susceptible to azoles, particularly voriconazole, and to amphotericin B (9,22), but reduced amphotericin B and itraconazole sensitivities have been described (23,24). In a large literature review of in vitro antifungal activities for reference antifungal agents on various fungi (23), MIC ranges for 18 isolates of P. parasiticum were 0.125 to 2 mg/liter for voriconazole, 0.125 to 16 mg/liter for amphotericin B, and 0.25 to 32 mg/liter for itraconazole.…”

“…However, Phaeoacremonium sp. in vitro susceptibility testing against antifungal drugs is not standardized, and methods for MIC determination and breakpoints still need to be established (9).…”