Association Between Vancomycin Use and Neutropenia in Pediatrics Patients

Corresponding Author Yara Neaimeh, MD, Department of Pediatrics, Division of Infectious Diseases, McGovern Medical School at UTHealth, 6431 Fannin St., MSB 3.126, Houston, Texas, 70030, USA, (713) 585-0033, yara.r.neaimeh@uth.tmc.edu Funding No funding was required for the project. Conflict(s) of Interest Yara Neaimeh, no conflict; Hoang Huynh, no conflict; Michael Chang, no conflict. Background Vancomycin-associated neutropenia is an uncommon side effect. Only five cases of vancomycin-associated neutropenia in pediatric patients have been described. The mechanism underlying this effect is unclear, though an immune-mediated response or direct bone marrow suppression are proposed. Recognizing this potential complication is crucial to optimize antibiotic selection and duration and minimize risk of adverse outcomes from antibiotic therapy. This report describes pediatric patients who developed neutropenia associated with vancomycin therapy. Methods This is a retrospective descriptive study of patients ≤18 years hospitalized at Children’s Memorial Hermann Hospital (CMHH) between January 1, 2018 to February 1, 2024. The study reviewed patients who received vancomycin for more than seven days and subsequently developed neutropenia, defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3. Patients with neutropenia due to immunocompromised conditions or those receiving immunosuppressive medications known to cause neutropenia were excluded. Data extracted from the CMHH electronic medical records included patient demographics, vancomycin and other anti-infective doses, neutropenia characteristics, outcomes and interventions. Results Nine patients were identified and 7 met the inclusion criteria while 2 were excluded. A patient with T-cell ALL with pre-existing neutropenia and another not on vancomycin at the time neutropenia developed were excluded. For the 7 patients included, Table 1 summarizes their demographics, vancomycin exposure and concurrent antibiotic use at the onset of neutropenia. Among them, 3 (43%) were only receiving vancomycin while 4 (57%) were receiving vancomycin alongside a cephalosporin, with or without an additional antimicrobial agent. The median duration of vancomycin therapy was 28 days, with a median of 21 days exposure prior to neutropenia onset. The median vancomycin dose was 16.7 mg/kg/dose and 58.6 mg/kg/day. There was a total of 91 vancomycin levels taken for these patients, where 69 (76%) were trough levels. Prior to neutropenia onset, trough levels ranged between 7.9-18.4 mcg/ml. After developing neutropenia, 2 (28%) patients completed their vancomycin course, 4 (57%) continued vancomycin therapy until course completion; of those, 1 patient was transitioned from ceftriaxone to cefepime. Uniquely, 1 (14%) patient was switched from vancomycin to daptomycin. Time to neutropenia recovery ranged between 3 to 8 days, though some patients lacked follow-up ANC measurement. The observed cases suggested an association between vancomycin monotherapy or combination therapy and the development of neutropenia, highlighting the need for careful monitoring. Conclusion Prescribers should be aware of vancomycin-associated neutropenia, though a rare side effect with unclear clinical impact. Our data shows that patients experienced a median of 21 days of vancomycin exposure prior to developing neutropenia with vancomycin trough levels ranging between 7.9 - 18.4 mcg/ml around time of neutropenia and ANC recovery ranging between 3 to 8 days. Whether vancomycin is administered alone or in conjunction with cephalosporin, careful monitoring is essential to ensure optimal outcomes.