Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations

Abstract

Introduction: Morbidity and mortality associated with invasive fungal infections (IFIs) remains unacceptably high. Such diseases represent a substantial burden to the healthcare system. New options are needed to address antifungal resistance in existing and emerging pathogens and improve treatment outcomes while minimizing drug-related toxicities and interactions. Awareness of new and potential future options is of great value for those healthcare professionals who care for patients with IFIs. Areas covered: A search of PubMed, infectious diseases conference abstracts and reference lists from relevant publications was conducted and relevant information abstracted. This review describes the limitations of existing systemic antifungal therapies (e.g., resistance, drug-drug interactions, drug-related toxicities) and summarizes data regarding several emerging antifungal compounds including (but not limited to) new triazoles (e.g. isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin Z. Agents in clinical trials such as (but not limited to) new triazoles (e.g., isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin are included. New formulations of existing drugs including reformulations of miconazole, posaconazole and amphotericin B are also reviewed. Finally, new or novel administration strategies for existing drugs such as combination antifungal therapy, antifungal dose escalation, adjunctive use of iron chelators and preemptive therapy are discussed. Expert opinion: All present antifungal agents have some deficiencies in antifungal spectra, toxicity, pharmacokinetics and/or drug-drug interactions, making them less than ideal for some fungal infections. Therefore, there remains an urgent need to find safe, effective, rapidly fungicidal, broad-spectrum antifungal agents with excellent pharmacodynamics to effectively eliminate the fungus from the body with short antifungal courses.

Particle-size distributions and seasonal diversity of allergenic and pathogenic fungi in outdoor air

“…Exposure to fungal allergens is considered to be a strong risk factor for asthma symptom prevalence and severity, and there is robust evidence to support a relationship between elevated environmental fungal spore counts and asthma attacks (Crameri et al, 2006;Denning et al, 2006). Although less common than allergic disease, invasive fungal infections occur in both immunocompetent and immunocompromised hosts (Pitman et al, 2011). Invasive fungal infections from Candidia, Aspergillus and Cryptococcus spp.…”

Clinical Candidate VT-1161's Antiparasitic Effect In Vitro , Activity in a Murine Model of Chagas Disease, and Structural Characterization in Complex with the Target Enzyme CYP51 from Trypanosoma cruzi

“…The safety and pharmacokinetics in humans have mirrored the data from preclinical studies with animals, insofar as VT-1161 appeared to raise no safety concerns and achieved an excellent pharmacokinetic profile when administered orally, exhibiting an extended half-life (23)(24)(25). All data obtained to date support the potential for VT-1161 to be a best-in-class CYP51 antifungal, overcoming the side effect profiles of the currently marketed fungal CYP51 inhibitors (26), which offer limited dosing options. The results of this study indicate the noteworthy anti-T. cruzi potency of VT-1161.…”

“…Second-generation azole antifungal drugs (e.g., itraconazole, voriconazole) utilized a 1,2,4-triazole. Compared to 1-imidazole, the 1,2,4-triazole was a lower-affinity ligand for heme iron, and this drug with an alternative MBG had improved tolerability, but liver toxicity and drug-drug interactions remained problematic (26). VT-1161 was discovered using a strategy to investigate new, more selective agents that focused on alternative, low-affinity MBGs.…”

Anti-infectious activity in plants of the genus Tabebuia

“…The decreased susceptibility of infectious agents to antimicrobials has warranted the need to increase the therapeutic arsenal of anti-infectious agents, emphasizing antibacterial, antiparasitic and antifungal agents (Gould 2008, Pitman et al 2011, Wise 2011. The scientific community and pharmaceutical companies have given medicinal plants special attention in the last years because of their promising potential to be used to develop innovative anti-infectious agents of natural origin (Osbourn 1996, Tagboto & Townson 2001, Ginsburg & Deharo 2011.…”