Acquired drug resistance during inadequate therapy in a young child with tuberculosis.

Drug resistance in children with tuberculosis is usually primary (transmitted); however, resistance acquisition during treatment is possible. We describe a child with tuberculosis who acquired drug resistance while receiving directly observed but inadequate first-line therapy and the programmatic and clinical factors that may have contributed to resistance acquisition.

Pharmacokinetics of isoniazid in low-birth-weight and premature infants.

Isoniazid (INH) is recommended for use as posttuberculosis exposure preventive therapy in children. However, no pharmacokinetic data are available for INH treatment in low-birth-weight (LBW) infants, who undergo substantial developmental and physiological changes. Our objectives in this study were to determine the pharmacokinetic parameters of INH at a dose of 10 mg/kg of body weight/day and to define its pharmacokinetics relative to the arylamine N-acetyltransferase-2 (NAT2) genotype.

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses.

Objectives: To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures.

Patients And Methods: We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines.

The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care.

Background: There is a paucity of data on the pharmacokinetics of fixed-dose combination enteral antituberculosis treatment in critically ill patients.

Objectives: To establish the pharmacokinetic profile of a fixed-dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol given according to weight via a nasogastric tube to patients admitted to an intensive care unit (ICU).

Methods: We conducted a prospective, observational study on 10 patients (mean age 32 years, 6 male) admitted to an ICU and treated for tuberculosis (TB).

Para-aminosalicylic acid plasma concentrations in children in comparison with adults after receiving a granular slow-release preparation.

There are no paediatric data regarding slow-release para-aminosalicylic acid (PAS). We studied PAS plasma concentrations in 10 children receiving a single 150 mg/kg dose daily or 75 mg/kg twice daily and 12 adults receiving 4 g twice daily. Blood specimens pre-dose and 2, 4, 6, 8 and 12 h post-dose from the children and 2, 3, 4, 5, 6, 8 and 12 h post-dose from the adults were analysed by high performance liquid chromatography MS/MS.