1342. Serial Microbial Cell-Free DNA Next Generation Sequencing (NGS) As A Means of Diagnosis and Monitoring of Clinical Response To Treatment Of Invasive Fungal Infections (IFI) In Immunocompromised Pediatric Patients

Abstract

Abstract Background IFIs are a leading cause of morbidity and mortality in immunocompromised pediatric patients. Early diagnosis and initiation of therapy is critical for treatment success but is often hindered by difficulty obtaining tissue samples, lack of growth on culture and time required for culture positivity. Non-culture methods such as aspergillus galactomannan and 1-3 B-D glucan lack sensitivity and specificity. NGS has shown promise in identifying a wide array of pathogens. The Karius test is a NGS which can identify viral, bacterial, and fungal infections by detecting cell free pathogen DNA in peripheral blood with a rapid turnaround time. Over the past few years we have used the Karius test as an adjunct to our standard of care in the workup and treatment of IFI in our oncology population Methods We report our experience in using serial NGS testing for diagnosis of IFI as well as a means for monitoring clinical response to treatment in our pediatric hematological malignancy population. Results Between 12/1/20-12/31/21, 5 patients had serial NGS for IFI. Most common indication for testing was prolonged fever and neutropenia with abnormal imaging. Initial diagnosis was made by NGS in all 5 patients. All had tissue biopsies with fungal elements seen on path in 4 of 5 patients. Culture was positive in 3 of 5 patients (2 days, 10 days and 12 days post NGS testing result). One patient with persistent positive NGS testing was found to have resistance to treatment drug on susceptibility testing and subsequently had negative NGS testing once appropriate antifungals were started. A second patient had sterilization of cultures with concomitant negative NGS results but developed increasing fungal copies on NGS testing followed by positive culture when chemotherapy was resumed and subsequently died due to his infection. 4 of 5 patients had serial negative follow up NGS and continue to do well. Summary of Diagnostic Work-Up Conclusion In our small series of patients, NGS testing allowed for rapid diagnosis of IFIs and corresponded to clinical response to treatment. Future prospective studies will be needed to further evaluate the use of NGS in this patient population. Disclosures All Authors: No reported disclosures.