CORRESPONDENCE

Linezolid dosing for staphylococcal pneumonia in children

To the Editor: We have noticed that the dose recommendation for linezolid use in our Guideline for VAP in children, recently published in the SAMJ,¹ is incorrect.

Results from studies in paediatric patients have demonstrated that there are age-related differences in the pharmacokinetic parameters of linezolid.² Children <12 years old have a smaller area under the Cmax curve (AUC), a faster clearance and a shorter elimination half-life than adults. Newborn infants have clearance values similar to those of adults. However, clearance increases rather markedly during the first week of life, to values 2 - 3 times in excess of those observed in older children and adults. The clearance of linezolid declines gradually in young children, becoming similar to that of adults by adolescence. After the age of 12 years, the pharmacokinetic parameters for linezolid are not significantly different from those of adults. The age-related changes in linezolid pharmacokinetics have implications for the appropriate dosing of the drug. These findings support the need for a shorter dosing interval in infants and young children to provide adequate drug exposure. In particular, more frequent administration will increase the AUC and plasma trough concentrations. This is important because the AUC:MIC ratio and the time above the minimum inhibitory concentration (MIC) are important determinants of linezolid efficacy against Gram-positive pathogens.

The recommended dosing guidelines for linezolid according to age are that, for most indications, children <12 years old should receive linezolid 10 mg/kg every 8 hours. The only exception to this is the treatment of uncomplicated skin and skin structure infections, for which the 8-hourly schedule is recommended only for children <5 years old. Because of the lower systemic clearance values and higher AUC values in preterm infants <7 days old, a dosing regimen of 10 mg/kg every 12 h should be initiated for these neonates. However, a 10 mg/kg every 8 h regimen should be considered for those with inadequate clinical response. In addition, the dosage should be changed to 10 mg/kg every 8 h for all neonates by the 7th day of life.

We trust this clarifies the issue.

Robin Green

Division of Paediatric Pulmonology and Intensive Care
Department of Paediatrics and Child Health
University of Pretoria and
Steve Biko Academic Hospital
Pretoria
robin.green@up.ac.za

Brenda Morrow

Andrew Argent

Argent Division of Paediatric Critical Care and Children's Heart Disease
School of Child and Adolescent Health
University of Cape Town and
Red Cross War Memorial Children's Hospital
Cape Town

Prakash Jeena

Division of Paediatric Pulmonology and Intensive Care
Department of Paediatrics and Child Health
University of KwaZulu-Natal and
Inkosi Albert Luthuli Hospital
Durban

1. Morrow BM, Argent AC, Jeena PM, Green RJ. Guideline for the diagnosis, prevention and treatment of paediatric ventilator-associated pneumonia. S Afr Med J 2009; 99: 253-267.         [ Links ]

2. Jungbluth GL, Welshman IR, Hopkins NK. Linezolid pharmacokinetics in pediatric patients: an overview. Pediatr Infect Dis J 2003; 22: S153-157.         [ Links ]