scholarly journals 574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S352-S352
Author(s):  
Molly Schiffer ◽  
Sarah Perreault ◽  
Dayna McManus ◽  
Francine Foss ◽  
Lohith Gowda ◽  
...  

Abstract Background Fever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data. Methods The patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions. Results Of the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p< 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities. Conclusion De-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections. Disclosures All Authors: No reported disclosures

AbstractAllogeneic hematopoietic stem cell transplantation (HSCT) and coronavirus disease 2019 (COVID-19) infection can both lead to severe cytokine release syndrome (sCRS) resulting in critical illness and death. In this single institution, preliminary comparative case-series study we compared clinical and laboratory co-variates as well as response to tocilizumab (TCZ)-based therapy of 15 allogeneic-HSCT- and 17 COVID-19-associated sCRS patients. Reaction to a TCZ plus posttransplant cyclophosphamide (PTCY) consolidation therapy in the allogeneic-HSCT-associated sCRS group yielded significantly inferior long-term outcome as compared to TCZ-based therapy in the COVID-19-associated group (P = 0.003). We report that a TCZ followed by consolidation therapy with a Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor given to 4 out of 8 critically ill COVID-19 patients resulted in their complete recovery. Non-selective JAK/STAT inhibitors influencing the action of several cytokines exhibit a broader effect than TCZ alone in calming down sCRS. Serum levels of cytokines and chemokines show similar changes in allogeneic-HSCT- and COVID-19-associated sCRS with marked elevation of interleukin-6 (IL-6), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1) and interferon γ-induced protein 10 kDa (IP-10) levels. In addition, levels of IL-5, IL-10, IL-15 were also elevated in allogeneic-HSCT-associated sCRS. Our multi-cytokine expression data indicate that the pathophysiology of allogeneic-HSCT and COVID-19-associated sCRS are similar therefore the same clinical grading system and TCZ-based treatment approaches can be applied. TCZ with JAK/STAT inhibitor consolidation therapy might be highly effective in COVID-19 sCRS patients.


2018 ◽  
Vol 12 (02.1) ◽  
pp. 10S
Author(s):  
Rima Moghnieh ◽  
Anas Mugharbil ◽  
Ali Youssef ◽  
Tamima Jisr ◽  
Hani Tamim ◽  
...  

Introduction: Bacterial infections are frequent complications occurring after autologous hematopoietic stem-cell transplantation (AHSCT). Herein, we identified the bacterial ecology and its antibiogram in AHSCT patients. We assessed the incidence, contributing factors and outcome of prolonged neutropenia and bacteremia post-AHSCT in the absence of antibacterial prophylaxis. Methodology: This is a retrospective chart review of 190 adult patients who underwent AHSCT for lymphoma and multiple myeloma, between 2005 and 2015 at a Lebanese hospital. Results: Most of the isolated bacteria originated from urine (49%) followed by blood (30%) and were mainly Gram-negative (70%). Fluoroquinolone susceptibility was 57% among Gram-negative and Gram-positive isolates. Bacteremia was documented in 12.6% of the patients, with a predominant gram-negative etiology having 95% susceptibility to fluoroquinolones. The duration of neutropenia, < or > 7 days, did not affect the incidence of bacteremia (11% vs. 14% respectively, p = 0.17). Patients with lymphoma were more likely to have prolonged neutropenia compared to those with myeloma (p < 0.0001). The use of a central line and the development of central-line infections were significantly higher in Gram-positive bacteremia (p = 0.03, p = 0.008 respectively). Mucositis occurred more in Gram-negative bacteremia (p = 0.02). Total mortality rate was 3.7% in the whole population and that attributed to bacteremia was 12.5% in the bacteremia subgroup. Bacteremia was a predictor for mechanical ventilation (p = 0.003), septic shock and mortality (p = 0.025). Conclusion: Since organisms causing bacteremia were still highly susceptible to fluoroquinolones and that the duration of neutropenia post-AHSCT didn't affect bacteremia, we concluded that fluoroquinolone prophylaxis is still valid yet, with close monitoring of resistance.


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