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In a multicenter retrospective study, we sought to determine the optimal vancomycin trough concentration that would impact the duration of methicillin-resistant Staphylococcus aureus bacteremia in children. We found that a median vancomycin trough concentration of <10 µg/mL within the first 72 hours may be associated with a longer duration of bacteremia compared to a median trough concentration of ≥10 µg/mL.

Acute graft-versus-host disease (aGVHD) refractory to high-dose corticosteroids is a major cause of morbidity and mortality in transplanted patients. The incidence of GVHD after allogeneic HSCT with HLA-matched marrow unrelated donor is between 70% and 80%, and this makes the basis for most of the GVHD literature. 1 GVHD is also an issue after solid organ transplantation (SOT) with incidence of about 5%-10% in small bowel transplant patients. 2 In a study by Mazarigeos et al, GVHD incidence was significantly higher in recipients who had liver included in the multiorgan transplant, suggesting that the liver may have a significant role in GVHD post-multivisceral transplant. 3 While we have a fair understanding of aGVHD, chronic GVHD (cGVHD) is less understood, although it is believed to involve alloimmune, autoimmune, and immune deficiency with inflammatory changes and increased activity of B lymphocytes leading to fibrosis. The current first-line treatment of GVHD in solid organ transplantation is corticosteroids along with lowering the patient's immunosuppression dose, allowing for the patient's own immune cell maturation to counteract the graft immunocompetent cells. 2 Similar to HSCT, no clear specific treatment options are available for steroid-refractory (SR) cases beyond the standard anti-T cell immunotherapies. JAK may be upregulated in inflammatory disease, and specifically, JAK 1 and JAK 2 have been implicated in the pathogenesis of aGVHD. In a study by Spoerl et al, JAK 1/2 inhibition by ruxolitinib improved survival in mice with

Achieving vancomycin troughs of 15-20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6-8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

Background: Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Bortezomib, a proteasome inhibitor that causes apoptosis of plasma cells, is an appealing targeted therapy in secondary AIHA and has demonstrated efficacy in HSCT patients. From our experience, we advocate for early targeted therapy that combines B cell with plasma cell depletion.Case Report: We describe a 4-year-old-girl with stage III neuroblastoma, complicated with intestinal necrosis needing multivisceral transplant developed warm AIHA 1-year after transplantation, and following an adenovirus infection. She received immunoglobulin therapy, rituximab, sirolimus, plasmapheresis, and long-term prednisolone with no sustained benefit while developing spinal fractures related to the latter therapy. She received bortezomib for intractable AIHA in combination with rituximab with no appreciable adverse effects. Three years later the child remains in remission with normal reticulocyte and recovered B cells. In the interim, she required chelation therapy for iron overload related to blood transfusion requirement during the treatment of AIHA. Conclusion:We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA. K E Y W O R D Santi-plasma cells, bortezomib, child, multivisceral transplant, refractory autoimmune hemolytic anemia AIHA data.From our experience and understanding of the immunopathogenesis mechanism that leads to secondary AIHA, we emphasize the need for early targeted therapy with combination of anti Blymphocyte and anti-plasma cell therapy in transplanted pediatric patients along with prednisolone and IVIG. This will reduce morbidity related to protracted therapies.