Background: Invasive pulmonary aspergillosis (IPA) is a leading cause of morbidity and mortality in immunocompromised oncohematology pediatric patients. This is mainly due to the absence of optimal diagnostic modalities, which hamper early specific disease detection and treatment. Thus, diagnosis of IA is still challenging and constitutes a major problem during management of pediatric patients at risk of infection, where the number of studies validating different diagnosis biomarkers is more limited. In a previous study, we demonstrated the high diagnostic accuracy of bis(methyl)gliotoxin(bmGT) compared to GM for IPA diagnosis in adults. The objective of this study is to show bmGT suitability for IPA diagnosis in oncopediatric patients in comparison with GM, monitoring the course of bmGT concentration in serum during voriconazole treatment.
Materials/methods: The presence and concentration of bmGT and voriconazole in sequential serum series from 9 oncopediatric patients with febrile neutropenia (retrospective and prospective samples) were simultaneously quantified by High Performance Thin Layer Chromatography (HPTLC) and confirmed using LC/MS/MS by an independent lab.
Results: HPTLC allowed simultaneous sensitive detection of bmGT and voriconazole in serum and BAL of pediatric patients confirmed by LC/MS/MS. We present two patients (17 and 36 months). In the phase of prolonged neutropenia, fever, hypoxemia and pulmonary infiltration compatible with Aspergillosis in high resolution CT are started. In one patient, bmGT was detected earlier than GM, allowing early initiation of treatment, with the voriconazole treatment the GM was negativized and the bmGT levels decreased. In the second patient, GM was negative and bmGT positive in serum and BAL, so treatment with voriconazole was started, then a decrease in bmGT values was detected coinciding with the patient clinical improvement.
Conclusions: The determination of bmGT in pediatric patients allowed the early diagnosis and effective treatment of two cases of IA, being a promising tool in neutropenic pediatric patients at risk of IPA. Identification of bmGT by HPTLC has been confirmed by LC/MS/MS indicating the presence of this biomarker during IPA in pediatric population. Analyses to establish the performance of serum bmGT detection together with beta-d-Glucan, PCR and IL8 to diagnose IPA in pediatric oncohematological patients are ongoing.
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Full conference title:
- ECCMID 30th (2020)