Paediatric use of second-line anti-tuberculosis agents: A review - 02/02/12

Doi : 10.1016/j.tube.2011.11.001

James A. Seddon ^a,^b,^⁎ , Anneke C. Hesseling ^a , Ben J. Marais ^c , Helen McIlleron ^d , Charles A. Peloquin ^e , Peter R. Donald ^f , H. Simon Schaaf ^a,^f
^a Desmond Tutu TB Centre, Faculty of Health Sciences, Stellenbosch University, South Africa
^b Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
^c Sydney Institute for Emerging Infectious Diseases and Biosecurity (SEIB) and the Children’s Hospital at Westmead, University of Sydney, Australia
^d Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa
^e College of Pharmacy, and the Emerging Pathogens Institute, University of Florida, USA
^f Tygerberg Children’s Hospital, Tygerberg, South Africa

Corresponding author. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Clinical Building, Room 0085, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa. Tel.: +27 722470795/213789177; fax: +21 219389792.

Summary

Childhood multidrug-resistant tuberculosis (MDR-TB) is an emerging global epidemic. With the imminent roll-out of rapid molecular diagnostic tests, more children are likely to be identified and require treatment. As MDR-TB is resistant to the most effective first-line drugs, clinicians will have to rely on second-line medications which are less effective and often associated with more pronounced adverse effects than first-line therapy. Despite the fact that most of these agents were discovered many years ago, robust information is lacking regarding their pharmacokinetic and pharmacodynamic properties, adverse effects and drug interactions, especially in children. Children differ from adults in the way that drugs are administered, the manner in which they are metabolised and in the adverse effects experienced. The interaction of these drugs with human immunodeficiency virus infection and antiretroviral therapy is also poorly documented. This article reviews the available second-line drugs currently used in the treatment of MDR-TB in children and discusses medication properties and adverse effects while potential interactions with antiretroviral therapy are explored.

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Keywords : Tuberculosis, Children, Drug-resistant, Second-line, Pharmacokinetics