Evaluation of the Risk of Recurrent Cefepime-Resistant Bacteremia in Pediatric Patients Receiving Hematopoietic Cell Transplantation

Abstract Corresponding Author Ashton Bellamy, Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, (903) 530-4509, abellamy@stjude.org Funding Supported, in part, by the National Institutes of Health Cancer Center Support (CORE) grant P30 CA021765 and the American Lebanese Syrian Associated Charities (ALSAC). Conflict(s) of Interest The authors of this study have no relevant conflicts of interest to declare. Background Children undergoing hematopoietic cell transplantation (HCT) are at high risk for antimicrobial-resistant infections. For post-HCT febrile events, current guidelines recommend modifying empiric antimicrobial regimens based on prior resistant infections, often leading to broader spectrum therapies being utilized. However, not all febrile episodes are associated with an infection. No high-quality evidence is available to guide the selection of empiric antimicrobials in this setting. The goal of this study is to estimate the proportion of recurrent, cefepime-resistant, Gram-negative infections in febrile post-HCT subjects with a prior cefepime-resistant history, and to investigate associations between clinical characteristics and the risk of recurrent infection. Methods This IRB-approved, retrospective cohort study evaluated infants, children, and adolescents (24 years) who had a cefepime-resistant Gram-negative bacteremia before or shortly after undergoing HCT between January 2010 and September 2022. We collected patient demographics, primary diagnosis, HCT details, presenting signs and symptoms, microbiological data, and antibiotic information for the initial cefepime-resistant bacteremia episode and for all subsequent post-HCT febrile events, regardless of neutropenic status, up to 100 days post-transplant. Recurrent episodes were excluded if the patient had received empiric treatment antibiotics within 48 hours prior to a new febrile episode. Results We identified 123 evaluable episodes in 63 unique patients. Sixty-three index episodes and 60 recurrent febrile episodes were included. Demographics are provided in Table 1. Recurrent cefepime-resistant infection occurred in 13/60 (21.7%) post-transplant febrile episodes. Thirty-eight of 60 (63.3%) episodes were culture negative, and 9/60 (15%) episodes were positive for a discordant bacterium (e.g., cefepime-susceptible or Gram-positive). Hypotension and receipt of a fluid bolus were significantly associated with an increased risk of recurrent cefepime-resistant infection (p=.0007 and 0.04, respectively). No other clinical features were associated with an increased risk. Characteristics are shown in Table 2. Conclusion Children and adolescents with a history of cefepime-resistant bacteremia who present with fever post-HCT are at risk of having another cefepime-resistant infection. Hypotension and receipt of fluid boluses are associated with a higher risk of developing recurrent bacteremia. Further research should aim to validate these findings, with the goal of developing risk stratification models to guide empiric therapy post-transplant.