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Clinical data on antifungal combination therapy are limited, in particular in the pediatric setting. We analyzed real-life data collected in two major pediatric cancer centers over a period of 4 years. Patients were identified in an observational study on children with acute leukemia and lymphoma or undergoing hematopoietic cell transplantation. Out of 438 patients, 19 patients received 21 episodes of antifungal combination therapy. Therapy was mostly started for sepsis (n = 5) or clinical deterioration with pulmonary infiltrates (n = 10), and less often for periorbital swelling with suspected mold infection (n = 2), clinical deterioration and new skin lesions, secondary antifungal prophylaxis, a persistently elevated galactomannan index, or as pre-emptive treatment (n = 1 each). Diagnostics revealed proven, probable, and possible invasive fungal disease in two, seven and four episodes, respectively. Most regimens included caspofungin (n = 19), and treatment was initiated as first line therapy in 10 episodes. The median duration was 13 days (4–46 days). Nine of the 13 patients with proven, probable, or possible invasive fungal disease survived, which was comparable to patients receiving antifungal monotherapy. Our analysis demonstrates that combination therapy has mainly been prescribed in selected immunocompromised patients with clinical deterioration due to suspected invasive fungal disease or those with sepsis, and is well tolerated. Future studies need to better characterize clinical settings in which patients may benefit from antifungal combination therapy.
Diagnostic approaches for invasive aspergillosis—specific considerations in the pediatric population
(2018)
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in children with hematological malignancies and those undergoing hematopoietic stem cell transplantation. Similar to immunocompromised adults, clinical signs, and symptoms of IA are unspecific in the pediatric patient population. As early diagnosis and prompt treatment of IA is associated with better outcome, imaging and non-invasive antigen-based such as galactomannan or ß-D-glucan and molecular biomarkers in peripheral blood may facilitate institution and choice of antifungal compounds and guide duration of therapy. In patients in whom imaging studies suggest IA or another mold infection, invasive diagnostics such as bronchoalveolar lavage and/or bioptic procedures should be considered. Here we review the current data of diagnostic approaches for IA in the pediatric setting and highlight the major differences of performance and clinical utility of the tests between children and adults.