Antifungal Therapies and Invasive Pulmonary Aspergillosis

Invasive pulmonary aspergillosis is a life-threatening fungal infection primarily affecting immunocompromised individuals, including transplant recipients, haematology patients and those receiving prolonged corticosteroid therapy. The disease arises when inhaled spores of Aspergillus species germinate within the lung, leading to tissue invasion, vascular occlusion and systemic dissemination. Current treatment relies on three major antifungal classes: polyenes (notably amphotericin B), triazole azoles (such as voriconazole and posaconazole) and echinocandins (for example caspofungin). Each class has distinct mechanisms of action, spectrum and toxicity profile, yet treatment failure remains common owing to drug resistance, suboptimal drug exposure at the site of infection and host factors. Recent efforts have focused on optimising dosing through pharmacokinetic–pharmacodynamic modelling, improving local delivery via inhaled formulations and developing novel agents with enhanced potency, reduced toxicity and activity against resistant strains. These advances promise to reshape therapeutic paradigms, reduce global morbidity and inform strategies for prophylaxis, combination therapy and individualised patient management.

Research from Nature Portfolio

Recent studies have demonstrated that combining a highly optimised inhaled triazole with systemic triazoles yields synergistic antifungal effects against Aspergillus fumigatus. In a human alveolar bilayer model, topical delivery of an inhaled azole markedly enhanced potency when paired with either posaconazole or voriconazole, outperforming monotherapy against both susceptible and resistant strains. In an immunocompromised mouse model, prophylactic and therapeutic co-administration significantly improved survival compared with single-agent regimens, suggesting that tissue retention of the inhaled agent augments efficacy. These findings support a novel combination strategy that exploits both local high lung concentrations and systemic coverage to overcome resistance and optimise clinical outcomes.

Antifungal Therapies and Invasive Pulmonary Aspergillosis publication trend

The graph below shows the total number of articles in antifungal therapies and invasive pulmonary aspergillosis across all publications each year (not limited to Nature Index journals).

Technical terms

Invasive pulmonary aspergillosis: A severe lung infection caused by Aspergillus species in immunocompromised hosts.

Azoles: A class of antifungal agents that inhibit fungal cytochrome P450–dependent 14α-sterol demethylase, disrupting membrane synthesis.

Echinocandins: Antifungal drugs that inhibit β-1,3-glucan synthase, weakening fungal cell walls.

Pharmacokinetics–pharmacodynamics (PK-PD): The study of drug concentrations over time and their relationship to antimicrobial effect.

Minimum inhibitory concentration (MIC): The lowest drug concentration that prevents visible fungal growth in vitro.

Galactomannan: A polysaccharide biomarker released by Aspergillus, used to monitor infection and treatment response.

References

1. Antifungal synergy of a topical triazole, PC945, with a systemic triazole against respiratory Aspergillus fumigatus infection. Scientific Reports (2019).
2. Assessment of Antifungal Pharmacodynamics. Journal of Fungi (2023).
3. Novel antifungal agents in clinical trials. F1000Research (2022).
4. Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent. Pharmacology Research & Perspectives (2020).