An analysis performed in children with TB indicates that some first-line drugs do not reach sufficient concentrations in the body to clear the infection. The study, led by Elisa López-Varela, researcher at ISGlobal, a centre supported by the "la Caixa" Foundation, and the Desmond Tutu TB Centre in South Africa, will help to design new, shorter and more effective anti-tuberculosis treatment regimens for children.
Tuberculosis (TB) is caused by a bacterium (Mycobacterium tuberculosis) that affects the lungs, as well as nearby lymph nodes. TB can be cured, but this requires a combination of different antibacterial drugs for several months. The drugs need to reach adequate concentrations in the lesions to eliminate the infection and prevent the development of resistant bacteria.
The treatment of children with pulmonary TB has been established based on studies in adults. "However, we know that the clinical spectrum of the disease in children and adults is different, and that the drug behaves differently in the body of a child than in that of an adult," says Elisa López-Varela. In this study, she and her colleagues in South Africa measured the concentration of four first-line drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) in blood, thoracic lymph nodes and bronchoalveolar fluid in 13 children with pulmonary TB who underwent bronchoscopy or lymph node surgery.
Lower concentrations in blood
The results show that the penetration of the drugs into tissues is similar in children and adults. However, at the doses currently recommended for children, drug concentrations in blood are lower than in adults, and therefore there is not enough drug reaching the infected tissues. Only one of the drugs (isoniazid) reached sufficient levels.
"This means that anti-tuberculosis treatment in children could be improved by using higher doses of rifampicin and ethambutol," says López-Varela. The study also provides the first data on ethambutol penetration in humans. "The drug penetrates well in tissue, but we need to use the highest recommended dose (25 mg/kg) in order to achieve sufficient drug concentrations in the lesions," she adds.
Although this is a small study, the data will help to design new, shorter and more effective anti-tuberculosis treatment regimens in children.
Lopez-Varela E, Abulfathi AA, Strydom N et al. Drug concentration at the site of disease in children with pulmonary tuberculosis. J Antimicrob Chemother. 2022 Apr 25. doi: 10.1093/jac/dkac103.