Abstract
Pulmonary mold infections are life-threatening diseases with high morbi-mortalities. Treatment is based on systemic antifungal agents belonging to the families of polyenes (amphotericin B) and triazoles. Despite this treatment, mortality remains high and the doses of systemic antifungals cannot be increased as they often lead to toxicity. The pulmonary aerosolization of antifungal agents can theoretically increase their concentration at the infectious site, which could improve their efficacy while limiting their systemic exposure and toxicity. However, clinical experience is poor and thus inhaled agent utilization remains unclear in term of indications, drugs, and devices. This comprehensive literature review aims to describe the pharmacokinetic behavior and the efficacy of inhaled antifungal drugs as prophylaxes and curative treatments both in animal models and humans.
Highlights
Bronchopulmonary invasive mold infections (IMI) are a major cause of mortality in immunocompromised patients such as transplant recipients and hematological patients with high-risk neutropenia [1,2]
Systemic triazoles and polyenes (amphotericin B (AmB)) are the classes of choice for prophylaxis and treatment, but they suffer from drug-drug interactions and toxicity, while echinocandins are poorly active against molds [3]
Based on the dosing capacity of each existing technology, only dry powder inhalers (DPIs) and nebulizers are capable of delivering the high dose needed to treat pulmonary fungal infections
Summary
Bronchopulmonary invasive mold infections (IMI) are a major cause of mortality in immunocompromised patients such as transplant recipients and hematological patients with high-risk neutropenia [1,2]. Aerosols are an interesting route of administration, theoretically limiting systemic toxicity while ensuring high concentrations at the site of infection [4]. Due to their physiochemical properties and pharmacokinetic characteristics, some antifungal agents are not good candidates for nebulization and should preferably be delivered intravenously. Triazoles, which have a high permeability across the respiratory barrier, are less attractive to inhale as a solution, since a low residence time in the lungs is obtained. Molecules with a high respiratory barrier permeability need to be delivered as solid particles with a slow dissolution/release rate, or as advanced formulations that can control permeability to increase their residence time in the lungs after inhalation [5]
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