Combination antifungal therapy for breakthrough invasive mould disease in patients with haematological malignancies: when management reasoning eclipses evidence-based medicine

Timely diagnosis and treatment of invasive mould disease is challenging in severely immunocompromised patients, particularly for patients who develop breakthrough infections while on antifungal prophylaxis. Currently, there are no high-quality data on how to best diagnose and treat these infections. Many essential decisions affecting the management of breakthrough mould disease are made before a definitive diagnosis is established. In this scenario, sound management reasoning often favours the use of combination antifungal therapy, especially when antifungal resistance, suspicion of undetected sites of infection or pharmacokinetic/pharmacodynamic limitations at the site of infection are likely. In these scenarios, pre-emptive use of antifungal combination therapy with frequent re-evaluation with an aim of de-escalation could be justified for many high-risk patients.