Isavuconazonium Sulfate Use in Multi-Modal Management of Invasive Mucormycosis in Four Pediatric Allogeneic Hematopoietic Cell Transplant Patients.

Prolonged neutropenia increases the risk for lethal invasive fungal infections (IFIs) such as those caused by Rhizopus species. Isavuconazonium sulfate is a new triazole that lacks pediatric dosing recommendations. Clinical courses of 4 pediatric patients with IFIs in the peri-allogeneic hematopoietic cell transplantation (alloHCT) period between 2015 and 2017 were reviewed. The reviews included previously unreported pharmacokinetic and safety data, and the IFIs included Rhizopus. Isavuconazonium sulfate was initiated with a loading dose followed by daily dosing, adjusted to a goal trough concentration of >3 mg/L based on adult literature. This target was achieved at a median of 7 days, demonstrating varying rates of metabolism. Renal insufficiency, electrolyte disturbances, and transaminitis were noted, although attribution was confounded by other alloHCT complications. One patient survived infection-free to hospital discharge and 1 of 3 deceased patients had evidence of an unresolved IFI (case 2). Case 2 was subtherapeutic for 39% of the duration of treatment, compared with others at an average of 29%, suggesting this target trough to be clinically relevant because case 2 demonstrated positive sinus and nasal cultures for Rhizopus on autopsy. We recommend initiation of isavuconazonium 10 mg/kg with a maximum dose of 372 mg. A loading dose of 10 mg/kg is used every 8 hours for 6 doses followed by 10 mg/kg dosing every 24 hours. Monitoring must continue beyond steady state. If early monitoring is not possible, we recommend a first drug level at week 3. If dose increases are required, a partial reload has been more successful instead of increasing daily doses. Further larger studies are needed to demonstrate optimum dosing in pediatric patients.

Continuous Antithrombin III Administration in Pediatric Veno-Arterial Extracorporeal Membrane Oxygenation.

The purpose of this retrospective case-control study is to determine the effect of continuous antithrombin III (ATIII) infusion on extracorporeal membrane oxygenation (ECMO) coagulation. All ECMO patients within the pediatric intensive care unit from January 2012 to July 2014 were included. Comparison was made between those who received continuous infusion ATIII through a standardized replacement protocol with historic controls receiving intermittent ATIII doses. Patients receiving the continuous infusion ATIII protocol spent more time in goal ACT range (71.9% vs 52.2%, p < 0.0001). Mean daily ATIII activity was also increased in study group (77.3% versus 68.6%, p = 0.04). No statistical differences in number of heparin dose changes per day (3 versus 3.22, p = 0.90) were present between the 2 groups. Only 28% of the historic controls receiving intermittent ATIII doses achieved normal ATIII activity as compared with 80% of study patients (p = 0.24). Maximum heparin dose was also lower in continuous infusion protocol group (p < 0.01). Compared with nonprotocolized intermittent dosing, the use of a continuous infusion ATIII protocol demonstrated increased time within goal ACT range at a lower heparin dose, no increase in hemostatic complications, and trends toward fewer heparin changes and lower blood product usage.