dLimited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment, serum concentrations following oral doses of levofloxacin (15 mg/kg of body weight) and ofloxacin (20 mg/kg) were lower than those expected from existing pediatric data, possibly due to differences in the formulations (crushed tablets). Drug exposures were lower than those in adults following standard doses and below the proposed pharmacodynamic targets, likely due to more rapid elimination in children. No QT prolongation was observed. Multidrug-resistant tuberculosis (MDR-TB) (i.e., resistance to rifampin and isoniazid) is an emerging epidemic with an estimated 63,000 pediatric cases per year (1, 2). Fluoroquinolones are essential in drug-resistant TB (DR-TB) treatment, but pharmacokinetic and safety data (including data on potential QT interval prolongation) for children are limited (3-6). South African DR-TB treatment guidelines were revised during 2012 to recommend levofloxacin (Lfx) and moxifloxacin (Mfx) instead of ofloxacin (Ofx) in children. Due to tablet sizes, children Ͼ8 years receive Mfx and children Ͻ8 years receive Lfx for prevention or treatment of DR-TB. We aimed to characterize the pharmacokinetics and cardiac effects of Ofx and Lfx in children Ͻ8 years of age.A prospective crossover intensive pharmacokinetic sampling study was conducted at Brooklyn Chest Hospital and Tygerberg Children's Hospital in Cape Town, South Africa from May 2012 through March 2013. Children aged 3 months to 8 years routinely started on either Ofx or Lfx for the prevention or treatment of MDR-TB were eligible. Exclusion criteria were a hemoglobin level of Ͻ8 g/dl or a weight of Ͻ5 kg. Child contacts (Ͻ5 years or HIV infected) of infectious MDR-TB cases without TB disease received preventive therapy, including 20 mg/kg of body weight Ofx or 15 mg/kg Lfx daily for 6 months. Children with MDR-TB received MDR-TB treatment based on World Health Organization recommendations (7). South African Medicines Control Council-approved tablets of Ofx (Tarivid, 200-mg tablets; Sanofi-Aventis, Midrand, South Africa) and Lfx (250-mg tablets; Cipla, Cape Town, South Africa) were used.Two pharmacokinetic samplings were done, alternately for Ofx and Lfx, both at steady state. Exact doses of Ofx of 20 mg/kg and of Lfx of 15 mg/kg were used, and the tablets were broken accordingly and weighed to the nearest 0.1 mg. After an overnight fast, tablets were given whole or crushed and suspended in water, and the dose taken was observed. Blood samples were collected predose and at 1, 2, 4, 6, and 8 h after dosing in EDTA-containing tubes and centrifuged, and plasma was separated and frozen within 30 min at Ϫ80°C. Lfx concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay developed in the Division

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Children with low-flow congenital heart lesions are reported to have an increased incidence of pulmonary tuberculosis. The aim of this study was to investigate if children with congenital heart disease have an increased incidence of pulmonary tuberculosis and to determine if patients with certain heart conditions are more susceptible to pulmonary tuberculosis than others. This retrospective study over a 6-year period showed that pulmonary tuberculosis was 2.5-fold more common in children with congenital heart disease than in normal children from the same community. Children with congenital pulmonary stenosis had a prevalence equal to those with acyanotic (ventricular and atrial septal defects) and cyanotic (transposition of the great arteries) high-flow heart lesions, whereas there were no cases of tuberculosis in children with low-flow cyanotic heart lesions such as tetralogy of Fallot. Cardiac surgery had to be postponed as a result of pulmonary tuberculosis in 7.2% of all patients in whom it was required. Over the 6-year period of the study, cardiac surgery had to be delayed in 60% of cases with pulmonary tuberculosis and congenital heart lesions so antituberculosis therapy could be completed. Physicians treating children with congenital heart lesions should maintain a high index of suspicion for the development of pulmonary tuberculosis, especially in those with acyanotic and cyanotic high-flow lesions and pulmonary stenosis.

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