Clinical use and safety profile of intravenous linezolid in hospitalised children: A retrospective cohort experience.

Evidence on the timing and burden of haematological adverse events with intravenous linezolid in children remains limited. We retrospectively evaluated paediatric inpatients aged 1 month and 18 years who received ≥ 3 days of IV linezolid at a tertiary children's hospital (September 2019-December 2022). Primary outcomes were anaemia and thrombocytopenia, defined a priori. Among 261 patients (median age, 6.9 years), 48.3% were treated in the PICU, and 39.1% had haematology-oncology disorders; the median treatment duration was 14 days. Anaemia (56.7%) and thrombocytopenia (41.8%) were the most common conditions, typically occurring in the first week. In multivariable models, anaemia was associated with concomitant myelotoxic drugs, prior exposure to glycopeptides, and concurrent thrombocytopenia; thrombocytopenia was associated with longer treatment duration and concurrent anaemia. Age-stratified analyses revealed similar early onset (median 6-7 days) across strata, with a higher frequency of thrombocytopenia in the youngest group, paralleling the more frequent concomitant use of myelotoxic therapy. In a restricted cohort excluding chemotherapy/HSCT and any myelotoxic agent (including meropenem), event rates declined while the early-onset pattern persisted. Analyses by treatment-duration categories (≤ 10, 11-14, ≥ 15 days) in patients with normal renal/hepatic function suggested a later onset of thrombocytopenia in the ≥ 15-day group; this subgroup also had the lowest rates of myelotoxic co-therapy, haematology-oncology comorbidity, and PICU admission, warranting cautious interpretation. Conclusions: IV linezolid was frequently associated with early haematological toxicity, amplified by concomitant myelotoxic therapy. Sensitivity and exposure-proxy analyses support the robustness of the signal but highlight residual confounding; prospective studies with exposure monitoring are needed to establish causality. What is Known: • In children, haematological adverse events are the most frequent toxicities of linezolid; thrombocytopenia is typically reported after week 1. • Paediatric evidence is limited and often confounded by concomitant myelotoxic therapies What is New: • In paediatric inpatients on IV linezolid, anaemia and thrombocytopenia often occur in week 1, with anaemia prominent when myelotoxic co-therapy or prior glycopeptides are present. • In a restricted cohort excluding myelotoxic co-therapy/chemotherapy, event rates declined, yet early onset persisted, supporting robustness beyond confounding.