Invasive Aspergillosis Resistant to Double-Coverage of Antifungal Therapy in a Very Immunosuppressed Lung Transplant Recipient

Abstract

<h3>Introduction</h3> Lung transplant (LT) recipients require intensive immunosuppressive regimens, which raises the risk of invasive fungal disease that can be challenging to clear. <h3>Case Report</h3> The patient is an 18-year-old male, bilateral LT (04/2021) recipient for cystic fibrosis, complicated by immediate posttransplant <i>de novo</i> DSA requiring plasma exchange and IVIG. At his 1-month post-discharge visit, significant DSA to multiple class I and class II alleles was found requiring augmented immunosuppression and admission for repeat inpatient plasma exchange and IVIG. Lavage cultures were remarkable for MDR-<i>Pseudomonas</i> with multiple subtypes, sensitive only to cefiderocol. Pulmonary function had not completely recovered since LT as FEV₁ had peaked at 1.5 L (47%) before dropping to 1.1 L (35%) in the current admission. Due to the ongoing DSA burden, we began treatment with antithymocyte globulin (ATG) to prevent the sequalae of antibody-mediated rejection. Additional imaging was remarkable for multiple, confluent, mass-like structures concerning for post-LT lymphoproliferative disorder, prompting biopsies that revealed angioinvasive <i>Aspergillus</i> (<b>Figure 1</b>). We started IV isavuconazole and continued cefiderocol, linezolid, and micafungin given his infectious history. The patient was symptomatic for dyspnea, which did not resolve despite the above antimicrobial coverage, prompting us to substitute voriconazole with some subjective improvement. Serial chest imaging showed worsening markings with new cavitation. Repeat lavage cultures were now significant for <i>Aspergillus terreus</i> and <i>Pseudomonas spp</i> superinfection. After nearly 2 months of ongoing IV antimicrobial therapy, we observed radiographic and symptomatic resolution. <h3>Summary</h3> Early DSA burden with decreasing pulmonary function justified treatment with ATG, but increased the risk of severe fungal infections, which required lengthy double-coverage antifungal therapy.