Here we report our experience with four paediatric patients with mediastinitis due to meticillin-resistant Staphylococcus aureus (MRSA) following cardiac surgery refractory to glycopeptide treatment and treated by linezolid. The pharmacokinetics and tolerance of linezolid administered orally or intravenously were analysed. Linezolid was administered intravenously at a dosage of 10 mg/kg every 8 h and then orally. In oral administration, 10 mg/kg or 15 mg/kg was given every 8 h as a powder made by crushing tablets. The linezolid serum trough concentration was >or=3.5 mg/L in patients treated by intravenous administration. However, with oral administration lower trough levels were detected, including patients with an undetectable level (<0.1 mg/L). No significant intolerance or drug-related haematological events were reported. We conclude that linezolid, with a switch from intravenous to oral administration, could be an effective and safe option in paediatric mediastinitis refractory to conventional glycopeptides, whilst care must be taken to maintain an adequate dose by monitoring the trough concentration.