Variability in Bacteremia Prophylaxis Use and Regimens in Pediatric Patients with Leukemia

Abstract Corresponding Author: Kathryn Carpenter, MD, Boston Children’s Hospital, 300 Longwood Avenue, Mailstop BCH3118, Boston, MA 02115, [email protected], 510-909-4734 Alternate corresponding author: Mari Nakamura, MD, MPH, Boston Children’s Hospital, 300 Longwood Avenue, Mailstop BCH3103, Boston, MA 02115, [email protected], 617-676-5089 No conflicts of interest Funding/support: Dr. Carpenter received support from the National Institutes of Health [Grant 5T32AI155391-03]. Dr. Nakamura received no additional funding. The sponsors of this work had no role in the study design, conduct, analysis, or interpretation of findings. Background Patients receiving chemotherapy for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are at high risk for bacteremia. Based on published evidence, the Children’s Oncology Group (COG) recommends use of levofloxacin prophylaxis in patients with AML and relapsed ALL who receive intensive chemotherapy, but prophylaxis for patients undergoing induction chemotherapy for ALL is not recommended. We conducted a survey of pediatric institutions to characterize the extent and timing of adoption of bacteremia prophylaxis for AML and ALL and assess variability in the antibiotic regimens used. Methods We distributed the survey via REDCap to US pediatric hospital-based antimicrobial stewardship programs in February – March 2023, identified based on their participation in the Sharing Hospital Antimicrobial Reports for Stewardship (SHARPS) collaborative and/or the Pediatric Health Information System (PHIS) database. We emailed the survey invitation to all known contacts for a program, often both physicians and pharmacists, but requested one response per hospital. In the event that recipients were not knowledgeable about bacterial prophylaxis practice patterns for leukemia patients, we encouraged them to work with others at their institution by forwarding the survey or filling it out together. We sent automated weekly reminder emails for three weeks to non-respondents. The survey included questions on prophylaxis regimens, inclusion criteria for prophylaxis, and timing of implementation, as well as any institutional evaluations of efficacy or safety. Results As of 3/13/24, surveys had been completed by 41% of hospitals (33/80). We are continuing recruitment with personalized individual emails. On interim analysis, we excluded one hospital that does not provide inpatient oncology care. Of the remaining 32 eligible hospitals, all reported that neutropenic patients with AML receive antibiotic prophylaxis. Levofloxacin monotherapy was by far the most common regimen (29/32, 91%), with many respondents (11/29, 38%) reporting implementation prior to September 2018, when the major pediatric randomized clinical trial on levofloxacin prophylaxis was published. Other hospitals did not adopt this practice until after publication of the trial (7/29, 25%) and of the COG guideline in July 2020 (7/29, 25%). One institution each reported regimens of levofloxacin and vancomycin [dosed every 12 hours]; cefepime [dosed every 12 hours]; and cefepime or levofloxacin for patients aged ≤12 years or >12 years, respectively. For neutropenic patients with ALL, most hospitals use prophylaxis in a subset of patients, typically those considered to be at high risk of bacteremia (25/32, 78%). Some hospitals provided prophylaxis to all patients with neutropenia (5/32, 16%), while two hospitals (6%) reported that no patients with ALL receive prophylaxis. Levofloxacin was the most commonly reported agent (28/30, 93%). One hospital reported use of levofloxacin for patients receiving high-dose cytarabine and penicillin otherwise. Another reported use of a different regimen but did not specify the antibiotic. Conclusions Levofloxacin prophylaxis has been widely adopted for pediatric AML patients with neutropenia. Prophylaxis for pediatric ALL patients with neutropenia is more variable, with most institutions using it only for those considered to be at high risk of bacteremia.