PC945, a novel inhaled azole for treatment of fungal tracheobronchitis post-lung transplantation: a case report

N Pagani 1, A Murray 2, P Strong 2, K Ito 2, G Rapeport 2, L Cass 2, M Carby 1, A Rice 3, AR Simon4, D Armstrong-James 5*, A Reed 1

Author address: 

1 Department of Respiratory and Transplant Medicine, Royal Brompton & Harefield NHS Foundation Trust, Harefield, UK, 2 Pulmocide Ltd., London, UK, 3Department of Cardiothoracic Transplant Pathology, Royal Brompton & Harefield NHS Foundation Trust, London, UK, 4 Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield, UK, 5 National Heart and Lung Institute, Imperial College London, UK.

Abstract: 

Background: The incidence of Aspergillus infections in lung transplant recipients has been reported to be up to 20%1. The commonest site for infection is the tracheobronchial area. The anastomotic site is particularly vulnerable due to disruption of blood supply to the donor airway and the presence of the sutures that act as a point of adhesion for pathogens. Bronchial anastomotic infections facilitate the retention of secretions and are a major risk factor for dehiscence, bronchial stenosis, fistulae and granulation tissue, potentially limiting the lung capacity2. The treatment of bronchial anastomotic infections with triazoles is challenging due to the drug-drug interactions with CNIs and risk of liver toxicity. The use of systemic amphotericin B is usually avoided in lung transplant recipients due to the increased nephrotoxicity while the nebulised administration is often hindered by tolerability issues.

Furthermore, the bronchial anastomosis remains ischemic post-transplantation, therefore the penetration to the site of infection of systemically administered antifungal agents is limited.

The aim of this report is to describe our experience in using a potent, novel inhaled azole agent PC945 (Pulmocide Ltd) to treat a proven fungal bronchial anastomotic infection 3, refractory to systemic antifungal treatment. PC945 is designed to deliver high pulmonary concentrations with retention in cells offering a long duration of action and minimal systemic exposure4.

2019

Poster: 

Full conference title: 

Fungal Update 2019
    • Fungal Update 2019