No abstract

BackgroundEmpirical antimicrobial regimens can be modified following new diagnostic information or when empirical treatment fails. Little is known about the frequency or clinical context in which these modifications occur. We characterised these modifications in a large animal hospital to identify when antimicrobial use could be optimised.MethodsChart reviews were performed for all inpatients and outpatients administered antimicrobials at a large animal veterinary referral and teaching hospital in 2017–2018 (n=1163 visits) to determine when and why empirical regimens were modified. Multinomial logistic regression was performed to identify factors associated with reasons for modification.ResultsEmpirical antimicrobial regimens were modified in 17.3 per cent of visits. The main reasons were parenteral-oral conversions in horses and failure of disease prevention or treatment in ruminants. Empirical therapy for disease prevention was more likely to be modified because of complications in ruminants and in animals on the emergency/critical care service. Empirical therapy for disease treatment was more often modified for reasons other than de-escalation in ruminants and in animals with longer lengths of stay.ConclusionsEmpirical antimicrobial regimens were modified infrequently and mostly for purposes of parenteral-oral conversion in horses and lack of response in ruminants. De-escalation of antimicrobials administered for disease treatment, when guided by diagnostics, is a major tenet of judicious antimicrobial use. However, more research is needed to determine when and how antimicrobial regimens administered for disease prevention should be modified.

Background: Epidemiologic studies in pediatric oncology have demonstrated disparities in Acute Lymphoblastic Leukemia (ALL) outcomes and survival for various ethnic minorities including Hispanic patients. While differences between outcomes and survival of different racial/ethnic groups in pediatric ALL is well documented, the impact of race/ethnicity on the incidence of methotrexate related toxicities in this population has not been fully described. Methotrexate, a mainstay of pediatric ALL regimens, has the potential to cause a variety of toxicities including myelosuppression, hepatic injury, acute kidney injury (AKI), mucositis, and central nervous system (CNS) injury. Recent literature suggests that Hispanic ethnicity may be associated with an increased risk of methotrexate toxicity, specifically neurotoxicity (Giordano (2017)). This project evaluated ethnicity associated with the incidence of methotrexate toxicities that could lead to dose reduction or delays in therapy such as grade 3 or 4 myelosuppression, hepatic injury, nephrotoxicity, and mucositis in patients receiving dose escalating methotrexate. Methods: A single-center, retrospective chart review was conducted at a 224 bed pediatric hospital. Patients were eligible for inclusion if they had a diagnosis of ALL and received intravenous (IV) dose escalating methotrexate between August 1, 2011 and March 31, 2019. Electronic medical records were used to identify eligible patients using medication identification numbers cross referenced with diagnosis codes. Toxicity data was collected to evaluate interruption in dose escalation of IV methotrexate due to grade 3 or 4 liver dysfunction, nephrotoxicity, mucositis, neutropenia, or thrombocytopenia. The primary outcome was percentage of doses which resulted in a dose-limiting toxicity. A two-sample t-test was performed for the primary outcome between Hispanic white and non-Hispanic white patients. Results: Of the 64 patients initially identified, 60 patients were included for final analysis. Two patients were excluded due to a diagnosis of Acute Biphenotypic Leukemia, one patient did not receive IV methotrexate per protocol due to delay in therapy and was subsequently ineligible, and one patient did not receive dose escalating methotrexate per protocol for unspecified reasons. A total of 460 doses were given to 60 patients. The sample size consisted of 22 non-Hispanic white, 21 Hispanic white, 9 Black, 3 Hispanic black, 1 Asian, 1 multi-racial, and 3 patients with unspecified ethnicity. The percentage of patients who experienced at least one toxicity was 58.3% (35 patients). The most common grade 3 or 4 toxicity experienced per dose was thrombocytopenia (6.5%), followed by neutropenia (6.3%), mucositis (1.3%), liver dysfunction (0.22%), and no patient experienced nephrotoxicity. When comparing the rate of toxicity between Hispanic and non-Hispanic patients, Hispanic patients experienced toxicity at a rate of 17.4% per dose compared to non-Hispanic patients at 12.2% per dose, although this was not a statistical significant difference (p = 0.61). Hispanic white and non-Hispanic white patients received the same amount of doses at 165 doses of IV methotrexate. Hispanic white patients experienced a toxicity rate of 19.4% per dose compared to 12.1% per dose in the non-Hispanic white patients. Hispanic white patients experience more thrombocytopenia, where as non-Hispanic white patients experienced more neutropenia. Although not statistically significant possibly due to small sample size, Hispanic ethnicity was associated with higher rates of methotrexate toxicities. Understanding the impact of methotrexate toxicity in respect to ethnicity is important to improving treatment outcomes for pediatric patients with ALL. More robust studies with a larger sample size are warranted to explore the potential impact of ethnicity on tolerability of this regimen. Disclosures No relevant conflicts of interest to declare.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer. Unfortunately, approximately 15% of children with high-risk B-cell ALL (B-ALL) relapse after frontline chemotherapy. Treatment of relapsed/refractory B-ALL is still challenging, and more effective novel therapies are urgently warranted. Blinatumomab, a first in class bispecific antibody therapeutic, has demonstrated superiority compared to standard chemotherapy in patients with B-ALL and has a manageable toxicity profile. Blinatumomab functions by binding to CD19 expressed on B-cells and CD3 expressed on T-cells, resulting in T-cell-mediated killing of CD19-positive cells common in B-cell malignancies. Despite remarkable efficacy and a manageable toxicity profile compared to standard-of-care chemotherapy, blinatumomab poses unique healthcare system challenges related to preparation, administration, toxicity monitoring, and medication error prevention. The drug's success in helping patients achieve complete remission relies on its continuous and uninterrupted administration. In order to ensure that it is delivered in the safest and most effective manner, education on its unique logistical and administration challenges is imperative. Objectives: The primary objective of this study is to describe and share the 6 years of institutional experience on the outpatient delivery of blinatumomab for the management of pediatric patients with B-ALL as per Children's Oncology Group protocols, as well as to retrospectively analyze the safety of this novel 28-day home-based therapy. Methods: A multidisciplinary team composed of physicians, nurses, and pharmacists was created to address administration challenges associated with blinatumomab infusions. Although blinatumomab requires a 28-day continuous infusion, it is not necessary for patients to remain hospitalized for the entire cycle. To ensure tolerability prior to discharge, patients are monitored closely during the first 3 days of Cycle 1 and 2 days of Cycle 2 for signs of cytokine release syndrome and neurological toxicities. Once discharged, they are seen every 96/72 hours for bag changes in either an outpatient hematology/oncology unit or by home health for those off study. Results: A total of 16 patients were treated with blinatumomab between May 2015 and June 2021; 10 were newly diagnosed and 6 were in first relapse. Of the 26 total infusions, 24 were successfully completed without significant adverse reactions. Two patients treated for relapsed disease had to discontinue therapy; one experienced neurotoxicity within 72 hours of blinatumomab infusion initiation and the other developed refractory disease and was switched to another protocol. No adverse events were observed in the home setting. Discussion: The team was successfully able to transform the original inpatient-only blinatumomab protocol to the outpatient setting. Retrospective analysis over 6 years demonstrates a clinically significant reduced rate of complications of blinatumomab administration in comparison to previous reports (Amicucci et al. 2021), which can be attributed to careful multidisciplinary team planning and delivery. This study confirms the feasibility of a home-based continuous blinatumomab infusion without adverse effects on safety. Additionally, this outpatient protocol leads to cost savings associated with reduced length of stay and an overall improved quality of life for pediatric patients able to receive therapy at home with their caregivers. Disclosures No relevant conflicts of interest to declare.