Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections

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.

Invasive Aspergillosis in the Intensive Care Unit

“…It has been shown to be highly effective against multiple fungal species, including Aspergillus , and shows superior activity to other azoles [ 112 ]. Opelconazole is an attractive option in patients who are at risk of IPA, including the growing cohort of patients being treated with immunosuppressive agents, as well as those with pulmonary disease, and patients with COPD, post-lobectomy, and post-transplant conditions [ 114 ]. Furthermore, its reassuring safety profile with low systemic absorption makes it a good candidate for combination therapy with the other novel agents being developed [ 115 ].…”

Severe Fungal Asthma: A Role for Biologics and Inhaled Antifungals

“…The polyene antifungal agent amphotericin B is highly active against Af but also as an intravenous agent is prohibitively nephrotoxic for required prolonged clinical use in allergic (non-invasive) muco-obstructive lung disease. This has led to exploration of off-label inhalational use of several intravenous formulations of amphotericin going back half a century, tried in various doses, regimes and aerosol delivery systems [ 55 , 56 ]. However, most of this experience arose in the context of immunosuppressed patients (e.g., lung transplant recipients, neutropenia, hematologic malignancy) at risk of or suffering from invasive aspergillosis or other mycoses.…”

Case report: Acute Talaromyces marneffei mediastinitis in an HIV-negative patient

“…Our patient failed to tolerate intravenous AmBd because she felt dizzy and her blood pressure dropped to 70/43 mmHg after the first infusion. As a result, we attempted to apply inhaled AmBd to the patient, for researches prove that nebulized AmBd can have been well-delivered in the bronchial and alveolar compartments with concentrations in BALF above most fungal MICs, and no or very weak systemic absorption is detected (Lowry et al, 2007;Brunet et al, 2022). These highlights of pharmacokinetics ensure nebulized AmBd to maintain its effect in the chest infection and limit its side reactions at the same time.…”