Nagel, Jerod

Abstract Background Febrile neutropenia (FN) is associated with a high risk for infections in patients receiving chemotherapy. Mortality estimates in pediatric patients with FN range from 0.4-3%. Extended infusion (EI) of beta-lactam antibiotics leads to improved pharmacodynamic parameters and is associated with enhanced antimicrobial activity. A recent study demonstrated significantly better overall treatment response in adult patients with documented infections and high-risk FN who received EI vs. standard infusion (SI) piperacillin-tazobactam. There are currently no studies evaluating clinical outcomes of EI beta-lactam use in pediatric patients with FN. Methods This study was a single-center retrospective cohort study with a time frame between September 2016-September 2022. The primary objective was to assess the time to fever resolution in patients with FN who received EI vs. SI of beta-lactam antibiotics. Secondary objectives included the difference in 30-day mortality and hospital length of stay (LOS) between the EI and SI groups. This study included patients admitted to pediatric hematology, oncology, or BMT services at Michigan Medicine who were (1) diagnosed with FN during hospital admission or admitted for FN following chemotherapy and (2) treated with EI or SI cefepime, piperacillin-tazobactam, or meropenem for at least 48 hours. Results A total of 87 patients were included in the study analysis (40 in the EI group and 47 in the SI group). Baseline characteristics were similar between the groups. There was no significant difference in the time to fever resolution for the cohort (48.5 vs 39.1 hours, p=0.373). There were numeric non-significant differences favoring EI for 30-day mortality (0% vs. 4%, p=0.496), and avoiding need to escalate antibiotic therapy due to treatment failure (7.5% vs. 17%, p=0.214). Conclusion The small sample size limited the ability to detect differences in time to fever resolution between EI and SI beta-lactams. Although not statistically significant, secondary endpoints showed numerically lower mortality and lower rates of therapy escalation in the EI group. Disclosures Madeleine King, PharmD, BCOP, Elsevier, Inc: Board Member

Abstract Background Contemporary information regarding fever and neutropenia (FN) management, including approaches to antibacterial prophylaxis, empiric therapy, and de-escalation across US cancer centers, is lacking. Methods This was a self-administered, electronic, cross-sectional survey of antimicrobial stewardship physicians and pharmacists at US cancer centers. The survey ascertained institutional practices and individual attitudes on FN management in high-risk cancer patients. A 5-point Likert scale assessed individual attitudes. Results Providers from 31 of 86 hospitals (36%) responded, and FN management guidelines existed in most (29/31, 94%) hospitals. Antibacterial prophylaxis was recommended in 27/31 (87%) hospitals, with levofloxacin as the preferred agent (23/27, 85%). Cefepime was the most recommended agent for empiric FN treatment (26/29, 90%). Most institutional guidelines (26/29, 90%) recommended against routine addition of empiric gram-positive agents except for specific scenarios. Eighteen of 29 (62%) hospitals explicitly provided guidance on de-escalation of empiric, systemic antibacterial therapy; however, timing of de-escalation was variable according to clinical scenario. Among 34 individual respondents, a majority agreed with use of antibiotic prophylaxis in high-risk patients (25, 74%). Interestingly, only 10 (29%) respondents indicated agreement with the statement that benefits of antibiotic prophylaxis outweigh potential harms. Conclusion Most US cancer centers surveyed had institutional FN management guidelines. Antibiotic de-escalation guidance was lacking in nearly 40% of centers, with heterogeneity in approaches when recommendations existed. Further research is needed to inform FN guidelines on antibacterial prophylaxis and therapy de-escalation.

Abstract Background Fever and neutropenia (FN) is common in cancer patients after chemotherapy, and there are national guideline recommendations for FN prevention and treatment. We conducted a survey of practices across multiple US cancer centers to determine the extent to which these guidelines have been adapted. Methods US cancer centers performing 20 allogeneic hematopoietic stem cell transplantations annually were identified from the National Marrow Donor Program’s “Be the Match” directory. Antimicrobial stewardship physicians and pharmacists at each institution were identified using institutional websites, residency or fellowship program directories, and personal contacts. A survey assessing institutional practices and individual attitudes on FN management in high-risk patients was distributed via email. Duplicate responses at the hospital level were removed. Complete surveys regarding individual attitudes were assessed using a 5-point Likert scale ranging from “Strongly Agree” to “Strongly Disagree.” Results Thirty-four (23%) responses from 148 individuals were received, representing 31 of 86 hospitals (36%). 29 (94%) hospitals reported having guidelines for the management of FN. Of these, cefepime was the most commonly recommended agent for empiric treatment (26, 90%) and 16 (55%) provide guidance based on presumed site of infection. Eighteen (62%) hospitals recommend de-escalation of Gram negative therapy in certain situations, most often after being afebrile 48 – 72 hours or after neutrophil recovery (7 each, 39%). Twenty-seven (93%) hospitals recommended antibiotic prophylaxis, most often with levofloxacin (21, 78%). Of 34 respondents, attitudes were split regarding the statement “The benefit of antibiotic prophylaxis outweighs the harms in high-risk patients” (10 strongly agree or agree, 10 strongly disagree or disagree; 29% each); most agreed with the statement “I would use antibiotic prophylaxis in high-risk patients” (25, 78%). Conclusion Most cancer centers across the US have guidelines for the management of FN. While most recommend antibacterial prophylaxis, there were differences in individual perceptions regarding the risk / benefit. Significant variation exists in the approach to antibiotic de-escalation. Disclosures All Authors: No reported disclosures