Posaconazole in the management of refractory invasive fungal infections

Abstract

The rising incidence of invasive fungal infections due to the expanding population of immunocompromised hosts and the increasing prevalence of fungal resistance has led to the need for novel antifungal agents. Posaconazole, a new member of the triazole class has demonstrated in vitro activity against a broad spectrum of fungi and clinical activity against various fungal pathogens, including Aspergillus spp., Candida spp., zygomycetes, and Fusarium spp. To date, posaconazole has been approved for prophylaxis of invasive fungal infections in stem cell transplant recipients with acute graft versus host disease (GVHD) and neutropenic patients receiving intensive induction chemotherapy for acute myelogenous leukemia and myelodysplastic syndrome. In addition, it has been licensed for use in oropharyngeal candidiasis and for salvage therapy in invasive aspergillosis, fusariosis, coccidioidomycosis, chromoblastomycosis, and mycetoma. Posaconazole is the only azole with activity against zygomycetes and other diffi cult-to-treat fungi, representing a potential treatment option for refractory invasive mycosis. This article reviews available preclinical and clinical data of posaconazole, focusing on its role in the teatment of refractory invasive fungal infections.

Outcomes of a Modified Treatment Ladder Algorithm Using Retrobulbar Amphotericin B for Invasive Fungal Rhino-Orbital Sinusitis

“…While extra-orbital surgical intervention was similar between the two groups, more patients in the post-2015 group were treated with posaconazole, presumably because the drug was approved for use in the United States in 2006. Possible synergy between posaconazole, caspofungin, and amphotericin B, [40][41][42] as well as a role for posaconazole in amphotericin-intolerant patients, 43 may have influenced outcomes. After adjusting for confounders, the lower risk of exenteration among the post-2015 group remained significant, whereas the relative risk of mortality remained similar.…”

Formulation and evaluation of posaconazole loaded nanostructured lipid carriers for topical drug delivery system

“…The reagents employed in research were analytical reagent grade Span 80, Tween 80, and other compounds. [33][34][35]…”

Candida Peritonitis: An Update on the Latest Research and Treatments

“…Of the newer extended‐spectrum triazoles, voriconazole and posaconazole are the only two currently available for use [92, 94–96]. The newer triazoles have improved safety profiles and a broad spectrum of activity, making them attractive choices for treatment [92–97, 99, 100]. Voriconazole has intravenous and oral preparations, whereas posaconazole is only effective when given orally [19].…”

“…Although well tolerated, voriconazole can cause hepatotoxicity, adverse visual events, and rashes [19]. Posaconazole can be used as salvage therapy for refractive infections and in rare cases can cause hepatotoxicity [19, 92, 96, 97]. For Candida strains with increased resistant to azoles, such as C. glabrata and C. krusei , echinocandins or preparations of amphotericin B can be used as alternatives [2].…”

“…In general, there are four classes of antifungal agents used in the medical management of Candida peritonitis: polyenes (deoxycholate and liposomal formulations of amphotericin B); azoles (fluconazole, itraconazole and the newer extended spectrum voriconazole and posaconazole); echinocandins (caspofungin, micafungin, and anidulafungin); and flucytosine [8,[92][93][94][95][96][97][98][99][100][101]. While selecting antifungal agents, clinicians should consider severity of the illness, the length of stay in the hospital, the type of peritonitis, recent exposure to antifungal agents, the resistance profile of the Candida species involved, relevant comorbid conditions (such as renal, liver, and bone marrow failure), and evidence of CNS, cardiac valve, and visceral organ involvement [94,95,102,103].…”