In Vitro Antifungal Susceptibility of Yeast and Mold Phases of Isolates of Dimorphic Fungal Pathogen Emergomycesafricanus (Formerly Emmonsia sp.) from HIV-Infected South African Patients

Abstract

Disseminated emmonsiosis is an important AIDS-related mycosis in SouthAfrica that is caused by Emergomyces africanus, a newly described and renamed dimorphic fungal pathogen. In vitro antifungal susceptibility data can guide management. Identification of invasive clinical isolates was confirmed phenotypically and by sequencing of the internal transcribed spacer region. Yeast and mold phase MICs of fluconazole, voriconazole, itraconazole, posaconazole, caspofungin, anidulafungin, micafungin, and flucytosine were determined with custom-made frozen broth microdilution (BMD) panels in accordance with Clinical and Laboratory Standards Institute recommendations. MICs of amphotericin B, itraconazole, posaconazole, and voriconazole were determined by Etest. Fifty unique E. africanus isolates were tested. The yeast and mold phase geometric mean (GM) BMD and Etest MICs of itraconazole were 0.01 mg/liter. The voriconazole and posaconazole GM BMD MICs were 0.01 mg/liter for both phases, while the GM Etest MICs were 0.001 and 0.002 mg/liter, respectively. The fluconazole GM BMD MICs were 0.18 mg/liter for both phases. The GM Etest MICs of amphotericin B, for the yeast and mold phases were 0.03 and 0.01 mg/liter. The echinocandins and flucytosine had very limited in vitro activity. Treatment and outcome data were available for 37 patients; in a multivariable model including MIC data, only isolation from blood (odds ratio [OR], 8.6; 95% confidence interval [CI], 1.3 to 54.4; P ϭ 0.02) or bone marrow (OR, 12.1; 95% CI, 1.2 to 120.2; P ϭ 0.03) (versus skin biopsy) was associated with death. In vitro susceptibility data support the management of disseminated emmonsiosis with amphotericin B, followed by itraconazole, voriconazole, or posaconazole. Fluconazole was a relatively less potent agent.

Antifungal Susceptibility of Emerging Dimorphic Pathogens in the Family Ajellomycetaceae

“…We limited antifungal susceptibility testing to the mold phase for the following reasons: (i) the pathogenic forms of these fungi differ greatly in the size and (ii) conversion time for some was very long and prone to contamination, with culturing for enough material taking longer than 1 month. Although it is a limitation that only the mold phase was tested, to our assurance recent studies of different endemic fungi using the mold and yeast phase for susceptibility testing found no differences in MICs between the two phases (8,24). This is the first comparative in vitro susceptibility study of five newly described taxa of dimorphic pathogens, Emergomyces orientalis, Emergomyces canadensis, B. percursus, B. helicus, and B. silverae, and of B. parvus and B. gilchristii.…”

“…Almost all infected human hosts were HIV infected. Emergomyces species differ from the other species within the same family by producing budding yeasts (less than 5 m) in vivo rather than adiaspores and often disseminate with secondary cutaneous manifestation, referred to as emergomycosis (8). Two species have been tested for antifungal susceptibility: Emergomyces africanus, the causative agent of an outbreak in South Africa (8,9), and Emergomyces pasteurianus (10).…”

“…Emergomyces species differ from the other species within the same family by producing budding yeasts (less than 5 m) in vivo rather than adiaspores and often disseminate with secondary cutaneous manifestation, referred to as emergomycosis (8). Two species have been tested for antifungal susceptibility: Emergomyces africanus, the causative agent of an outbreak in South Africa (8,9), and Emergomyces pasteurianus (10). Emergomyces infections have been treated mostly with amphotericin B, itraconazole, or fluconazole (4, 11; S. Sanche, A. Wong, L. Sigler, S. Angel, and S. Peterson, presented at Focus on Fungal Infections, Miami, FL, 2005, abstract 87) but no clinical trial has been conducted to date.…”

Name Changes for Fungi of Medical Importance, 2016–2017

“…Emergomyces africanus was described as an Emmonsia species when it was first isolated in 1995 (15). By 2017, over 80 cases had been diagnosed in South Africa (16), where it is now considered to be the most common endemic mycosis (14). Only one case each of Emergomyces europaeus and Emergomyces orientalis infections have so far been reported (13,17), while Emergomyces canadensis has recently been described from four cases of invasive disease among immunocompromised individuals in western Canada and the United States (18).…”

Emergomyces africanus in Soil, South Africa

“…[ 2 ]) is the species responsible for the most human disease. HIV-associated emergomycosis is the most common endemic mycosis in South Africa and is associated with a high case-fatality ratio ( 3 , 4 ). …”