In Vitro Activities of Posaconazole, Itraconazole, Voriconazole, Amphotericin B, and Fluconazole against 37 Clinical Isolates of Zygomycetes

Abstract

In vitro antifungal susceptibility testing results of a new antifungal triazole, posaconazole (POS), were compared to results with amphotericin B (AMB), itraconazole (ITC), voriconazole (VRC), and fluconazole (FLC) against clinical agents of zygomycosis. The MICs of POS at which 50% and 90% of the isolates were inhibited were 0.25 and 4 g/ml, respectively. POS was significantly more active than VRC and FLC and slightly more active than ITC. The results suggest that POS has significant potential for clinical development against the zygomycetes.Invasive mycoses have increased dramatically over the past several years, largely as a result of increasing numbers of immunosuppressed patients. The zygomycetes are less common causes of invasive human infection compared to Aspergillus spp. and Candida spp. In several large studies of the occurrence of fungal infection in high-risk populations, infections with zygomycetes represented 5 to 12% of all fungal infections (1, 14), while in another study, zygomycosis represented up to 25 to 44% of all invasive fungal diseases (6, 9). The manifestations of zygomycosis include primary rhinocerebral, pulmonary, gastrointestinal, cutaneous or subcutaneous, or allergic disease and disseminated disease (11). Amphotericin B (AMB) is the first-line therapy of choice for most cases of zygomycosis, but its use is limited by its potentially severe side effects.In the study described here, we compared the in vitro activities of four triazoles and AMB against 37 clinical isolates of zygomycetes. The isolates included 7 isolates of Mucor spp., 10 isolates of Rhizopus spp., 5 isolates of Absidia coryambifera, 5 isolates of Cunninghamella spp., 4 isolates of Apophysomyces elegans, 2 isolates of Cokeromyces recurvatus, and 4 isolates of Saksenaea vasiformis. All isolates came from the Fungus Testing Laboratory at The University of Texas Health Science Center (UTHSC) at San Antonio. Isolates were retrieved from storage at Ϫ70°C or from water stocks and were subcultured onto slants of potato flake agar with incubation at room temperature until adequate growth was obtained. Paecilomyces variotii strain UTHSC 90-459 was used as a control. MIC endpoints were read visually after 24 and 48 h of incubation. Standard antifungal powders of posaconazole (POS; ScheringPlough), voriconazole (VRC; Pfizer), fluconazole (FLC; Pfizer), itraconazole (ITC; Janssen), and AMB (Bristol-Myers Squibb) were obtained from their respective manufacturers. Stock solutions of POS, VRC, and ITC were prepared in polyethylene glycol 400, while AMB and FLC were dissolved in water. Final dilutions of POS, VRC, FLC, and ITC were made in RPMI 1640 medium with L-glutamine and morpholinepropanesulfonic acid buffer (Angus Chemical Co., Niagara Falls, N.Y.). AMB was made with Antibiotic Medium 3 (Difco). Serial twofold dilutions of each antifungal agent were prepared to the following final drug concentrations: AMB, 0.03 to 16 g/ml; POS and ITC, 0.015 to 8 g/ml; FLC and VRC, 0.125 to 64 g/ml. Stock solutions of these drugs were stored a...

Mucormicosis cutánea primaria: a propósito de dos casos. Revisión de la literatura

“…En el primer caso presentando, no disponiendo de formas lipídicas de anfotericina, se ajustó la dosis a emplear de acuerdo a la función renal del paciente, lo que determinó una menor biodisponiblidad del medicamento y un menor efecto fungicida; pudiendo explicar en parte esta variable su desenlace fatal. Otra alternativa terapéutica, hoy en día, está representada por un nuevo azol: posaconazol, el cual ha demostrado buena actividad in vitro frente Rhizopus, Mucor y otras especies de Zygomycetes, existiendo reportes con resultados promisorios en el tratamiento de mucormicosis, tanto en monoterapia o bien como coadyuvante a la terapia con anfotericina; sin embargo, se requiere de mayor evidencia científi ca que permita validar estos resultados [22][23][24][25][26][27] .…”

ZIGOMICOSIS CUTANEA PRIMARIA POR Rhyzopus oryzae EN UNA NIÑA CON LEUCEMIA LINFOBLASTICA AGUDA TIPO B

“…Por el contrario, en el paciente inmunocomprometido las lesiones, rojas e induradas, progresan formando costras negras que, al desprenderse, dejan úlceras grandes. La preferencia angioinvasiva de los zygomycetes, con la consecuente diseminación por debajo de las estructuras cutáneas, culmina con la necrosis rápida y progresiva no sólo de los tejidos cutáneos y subcutáneos, sino también de la grasa, músculos, tendones, el hueso adyacente y seguir un curso fulminante (3,12,15,23,26,30,31).…”

“…Por otra parte, el diagnóstico de especie hasta ahora no parecía tener mayor trascendencia clínica; sin embargo, existen diferencias significativas de susceptibilidad in vitro de los distintos géneros y especies de la familia Mucoraceae a los azoles, lo que podría traducirse dentro de los próximos años en importantes decisiones terapéuticas (6,30).…”

Rhinocerebral Mucormycosis Treated with Posaconazole: A Case Report

“…Posakonazol, zigomisetlere in vitro etkili olduğu gösteri-len, oral yoldan kullanılabilen, geniş spektrumlu azol grubu yeni bir antifungal ajandır (9,10). Standard antifungal tedavilere dirençli mukormikoz olgularında kurtarma tedavisinde başarıyla kullanılmıştır (11)(12)(13).…”