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Posaconazole: a new antifungal weapon
Georgios Aperis1, Polichronis Alivanis
1Department of Nephrology, General Hospital of Rhodes, Greece. gaperis@yahoo.com
Abstract:
The last twenty years, the incidence of invasive fungal infections (IFI) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections. Amphotericin B was for more than 40 years the gold standard for almost all IFI, but toxicity and resistance, especially of new and emerging pathogens remained important issues. Fluconazole and itraconazole have also the same disadvantage of resistance. Voriconazole, a new triazole antifungal has offered an additional option, but the problem of resistant aspergillosis, and zygomycosis remains. Echinocandins (caspofungin, micafungin and anidulafungin) are active only against Candida and Aspergillus spp., but not against Fusarium, Scedosporium and Zygomycetes. Posaconazole is the most recently approved triazole with broad spectrum activity against Candida spp., Aspergillus spp., Cryptococcus neoformans, Zygomycetes, dermatiaceous, dimorphic, and other fungal pathogens. Interestingly, posaconazole is active against Candida spp., resistant to fluconazole and itraconazole, and Aspergillus fumigatus resistant to fluconazole itraconazole, amphotericin B, and voriconazole. The results from clinical trials of posaconazole as salvage treatment are encouraging. Multicenter clinical trials have also established its role in the prophylaxis of (IFI) in the severely immunocompromised patients such as those after hematopoietic stem cell transplantation (HSCT) who developed graft versus host disease (GVHD), as well as the neutropenic patients with an acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after myeloablative chemotherapy. Posaconazole has pharmacokinetic advantages and low side effect profile, which are very important, especially in the seriously ill population.
Insights
Posaconazole offers broad-spectrum antifungal activity, effectively treating resistant invasive fungal infections (IFI). Clinical trials show its efficacy in salvage therapy and prophylaxis for immunocompromised patients, with favorable pharmacokinetics and safety.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive fungal infections (IFI) have increased due to longer survival in high-risk patients.
- Traditional antifungals like Amphotericin B, fluconazole, and itraconazole face issues with toxicity and emerging resistance.
- Newer agents like voriconazole and echinocandins have limitations against specific pathogens.
Purpose of the Study:
- To evaluate the efficacy and safety of posaconazole, a broad-spectrum triazole antifungal.
- To assess posaconazole's role in salvage treatment and prophylaxis of IFI in immunocompromised populations.
Main Methods:
- Review of clinical trial data for posaconazole in treating and preventing IFI.
- Analysis of posaconazole's activity against various fungal pathogens, including resistant strains.
- Evaluation of posaconazole's pharmacokinetic profile and side effect profile.
Main Results:
- Posaconazole demonstrates broad-spectrum activity against Candida, Aspergillus, Cryptococcus, Zygomycetes, and other fungi.
- It is effective against fungal strains resistant to older antifungals.
- Clinical trials support its use in salvage therapy and prophylaxis for neutropenic patients and post-hematopoietic stem cell transplantation patients.
Conclusions:
- Posaconazole represents a significant advancement in managing invasive fungal infections.
- Its broad spectrum and activity against resistant pathogens offer a valuable therapeutic option.
- Favorable pharmacokinetics and a low side effect profile enhance its utility in critically ill patients.
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