Aspergillus to Zygomycetes: Causes, Risk Factors, Prevention, and Treatment of Invasive Fungal Infections

Abstract

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with underlying risk factors (e.g., neutropenia, cancer chemotherapy, transplantation, AIDS). Although Candida species remain a relevant cause of IFI, other organisms (particularly moulds) have become increasingly prevalent. In particular, Aspergillus species are the leading cause of mould infections although other moulds including Fusarium species and Zygomycetes are increasing in frequency, and are associated with a high mortality rate. Options available for the prevention and treatment of these infections include standard and liposomal formulations of amphotericin B, but toxicity concerns limit their use; fluconazole is effective for the prevention and treatment of candidiasis but its inactivity against moulds and increasing resistance are limiting factors. Newer azoles, particularly voriconazole and posaconazole, have an enhanced spectrum of activity that includes Candida species, Aspergillus species, Cryptococcus species, dimorphic fungi, Fusarium species, and, for posaconazole, Zygomycetes. Recent data suggest that these agents are highly effective in a variety of clinical settings. Echinocandins have good activity against Candida species and Aspergillus species but their spectrum generally does not include Fusarium species, Cryptococcus species, Trichosporon species, Zygomycetes, and dematiaceous moulds. While these agents are unlikely to exhibit crossresistance with polyenes or azoles, they must be administered intravenously. Knowledge of the pathogenesis of IFIs and the activity, efficacy, and limitations of available treatment options will allow the selection of an appropriate antifungal agent for individual patients.

Long-term treatment of invasive sinus, tracheobroncheal, pulmonary and intracerebral aspergillosis in acute lymphoblastic leukaemia

“…In particular, the incidence of aspergillosis is increasing among patients with acute leukemia and patients undergoing stem cell transplantation [1][2][3][4][5][6]. Many factors contribute to this rise in fungal infections, including the treatment of patients at a higher age, more co-morbidities and more complex interventions.…”

Diagnostik invasiver Pilzinfektionen/Diagnosis of invasive fungal infections

“…Bei der allogenen Transplantation besteht das h ö chste Risiko f ü r Patienten mit h ö hergradiger GvHD. Auch eine CMV-Erkrankung erh ö ht das Risiko [2,24] .…”

“…Mucormycotina , Fusarium spp., oder Scedosporium/Pseudallescheria spp. sind selten, sollten aber differentialdiagnostisch bei Risikokonstellation [Immunsuppression, Diabestes mellitus und H ä mochromatosen [ Mucoromycotina ], Beinahe-Ertrinkungsunf ä llen ( Scedosporium/Pseudallescheria )] in Betracht gezogen werden [2] . Der Nachweis erfolgt histologisch und kulturell, Antigennachweise stehen nicht zur Verf ü gung.…”

“…eine l ä nger ( > 10 Tage) anhaltende Neutropenie, eine systemische Therapie mit Steroiden und -insbesondere bei Candida spp. -eine l ä nger durchgef ü hrte intensivmedizinische Therapie mit invasiver Instrumentierung [2] . Die klinischen Zeichen einer invasiven Mykose sind unspezifi sch und auch radiologisch ist beispielsweise eine Aspergillose selten eindeutig zu diagnostizieren.…”

Synthesis and in vitro and in vivo Antifungal Activity of the Hydroxy Metabolites of Saperconazole

“…Moreover, posaconazole shows efficacy against infections caused by emerging species of Zygomycota. [24] Echinocandins such as anidulafungin, caspofungin, and micafungin, which are noncompetitive inhibitors of 1,3-b-glucan synthesis in fungal cell walls, display high efficacy against Candida and Aspergillus spp., but have no activity against Cryptococcus, Fusarium, or Zygomycetes spp. [25,26] Of all antimycotic agents, azoles still represent a unique class of compounds that display the broadest antifungal spectrum via inhibition of 14-a-demethylase, an enzyme essential for ergosterol biosynthesis in fungi.…”