A pharmacokinetic model proposes tedizolid doses for children, pending trials

Design

Physiologically based pharmacokinetic modelling and dose simulation, validated against independent clinical data

Population

Simulated adults and children aged 2 to 18 years with skin and soft-tissue infection, immunocompetent

Primary outcome

Probability of target attainment (fAUC/MIC of 3 or more) across MICs of 0.125 to 16 mg/L

Effect

At MIC 0.5 mg/L: 4 mg/kg or more (2 to under 12 years); 200 mg or 3 mg/kg (12 to under 18 years) gave at least 90% attainment

Researchers built a physiologically based pharmacokinetic model of tedizolid, an oxazolidinone approved for acute bacterial skin and skin structure infections, first in adults and then scaled to children aged 2 to 18. The model's predicted exposures were all within twofold of observed values, and it was checked against independent paediatric data.

Simulating once-daily intravenous and oral regimens against a target of free drug exposure to MIC ratio of 3 or more, they found that for children aged 2 to under 12 years, doses of 4 mg/kg or more reached at least 90% probability of target attainment at an MIC of 0.5 mg/L. For adolescents aged 12 to under 18 years, a fixed 200 mg dose or 3 mg/kg did so.

These are model-derived candidate regimens in immunocompetent patients, not tested doses. The authors support clinical evaluation; they do not claim these doses are safe or effective in children.

• Do not use these simulated doses in clinical care; they are candidates for trials
• Check the licensed age range and dosing in your local product information
• Target attainment at an MIC of 0.5 mg/L says nothing about organisms with higher MICs
• Immunocompromised children were outside the model

Why it matters

Most antibiotics reach children long after adults, and modelling is how dose-finding is increasingly started.

Don't overread it

A simulation cannot establish efficacy or safety in children, and the doses are not validated by a trial.

The statistics, in plain English

Probability of target attainment is the share of simulated children who would reach the exposure thought to be effective, given an organism's MIC. A twofold error range for prediction is the usual regulatory standard for such models; it still allows meaningful over- or under-exposure in an individual.

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