Continuous-Infusion Foscarnet Facilitates Administration in Hematopoietic Stem Cell Transplantation Patients

Abstract

Infections due to herpesviruses resistant to first-line antivirals remains an ever-present and serious complication in recipients of hematopoietic cell transplantation (HCT) and other cellular therapies. Foscarnet is the most common therapy for patients who have resistant herpesvirus infections or intolerable cytopenias due to ganciclovir or valganciclovir; however, the widespread use of foscarnet is limited by its associated nephrotoxicity and challenges in administration. In the earliest published small case series investigating the optimal infusion modality, patients with acquired immunodeficiency syndrome (AIDS) due to the human immunodeficiency virus (HIV) received either continuous infusion or intermittent dosing of foscarnet. Moreover, there was no standardization of hydration strategies to minimize side effects. Eventually, intermittent foscarnet infusions became the standard of care; however, the true impact of hydration and infusion duration on nephrotoxicity has not been adequately studied, and the reports of foscarnet administration in HCT patients has been limited primarily to intermittent infusions. In this report, we characterize the administration of foscarnet as a 24-hour continuous infusion in both the inpatient and outpatient settings compared with intermittent infusion in HCT recipients. This retrospective, single-center, observational study at Stanford University Medical Center assessed HCT recipients who received foscarnet between January 2009 and May 2019. Twenty-eight of 45 patients (62.2%) who received continuous-infusion foscarnet experienced an acute kidney injury (AKI) as defined by the Kidney Disease Improving Global Outcomes classification, compared with 39 of 62 patients (62.9%) who received conventional infusion (P=.94). The average duration of outpatient antiviral days for the continuous infusion group was 9 days (range, 0 to 121 days), compared with 6.3 days (range, 0 to 70 days) in the intermittent infusion group (P=.54). Our findings suggest that foscarnet given as a continuous infusion or as an intermittent infusion have similar rates of adverse reactions, most notably similar rates of AKI. Administering foscarnet as a continuous infusion is a feasible option to facilitate outpatient treatment.