Real-world challenges and unmet needs in the diagnosis and treatment of suspected invasive pulmonary aspergillosis in patients with haematological diseases: An illustrative case study.

Recent years have seen important advances in the diagnosis of invasive pulmonary aspergillosis (IPA), complemented by the introduction of new therapies. Despite this, IPA remains a major cause of infection-related mortality in patients with haematological diseases. There are two main reasons for this. First, diagnosis of IPA remains a challenge, since risk factors and the clinical, radiological and mycological presentations vary not only by fungal disease stage, but also by patient group (eg neutropenic vs non-neutropenic patients). Diagnosis is particularly challenging in patients receiving mould-active prophylactic or empirical treatment, which reduces the sensitivity of all diagnostic tests for IPA. Second, treatment of IPA is complex due to unpredictable pharmacokinetic profiles of antifungal agents, small therapeutic window in terms of exposure and adverse events, and multiple drug-drug interactions through the CYP450 system. Here we report a case of a 23-year-old male with severe aplastic anaemia and subpleural nodules. Diagnostic tests for IPA obtained during ongoing mould-active empirical treatment were negative. Intravenous voriconazole was stopped after visual disturbances and hallucinations. The patient then had an anaphylactic reaction to liposomal amphotericin B and was switched to intravenous posaconazole, which had to be discontinued due to a significant increase in transaminase levels. He was treated with oral isavuconazole with reduced dosage, triggered by increasing transaminases under the standard dosage. Even under reduced dosage, blood concentrations of isavuconazole were high and treatment was successful. The case illustrates real-world challenges and unmet needs in the diagnosis and treatment of IPA in patients with haematological diseases.