Abstract
Three major institutes in Thailand, including King Chulalongkorn Memorial Hospital, Queen Sirikit National Institute of Child Health, and Faculty of Medicine, Chiang Mai University, worked in collaboration to establish the management plan for drug-resistant tuberculosis in children mainly consists of two paralleled projects, including the prevalence of drug-resistant tuberculosis in Thai children and the study of pharmacokinetics and safety of levofloxacin in pediatric tuberculosis treatment. The prevalence study of drug-resistant tuberculosis in Thai children had screened 186 children during 2019 and 2021, of which 104 children were diagnosed with tuberculosis, including 11 children with any forms of drug-resistant tuberculosis; 7 (7%) children were resistant to isoniazid, 2 (2%) were rifampicin, and 1 (1%) was multi-drug-resistant. In comparison with the medical records data from Siriraj hospital (the year 2009 to 2011) and Queen Sirikit National Institute of Child Health (the year 2001 to 2010), the prevalence tended to decrease over time. As a result, the prevalence of tuberculosis in children was similar to that in adults in 2017-2018. Thus, the characteristics of tuberculosis in children may represent those in adults. Moreover, the majority of drug resistant tuberculosis in children is isoniazid resistant tuberculosis which may reflect the similar prevalence of isoniazid-resistant tuberculosis in adults. The current World Health Organization’s recommendation and the Thai National tuberculosis management guidelines have implemented the treatment regimen of rifampicin, pyrazinamide, ethambutol, and levofloxacin for 6 months for isoniazid resistant tuberculosis has been shown to reduce the mortality and recurrent rates. However, the current application of molecular diagnosis as Xpert MTB/RIF could not detect isoniazid-resistant tuberculosis. Therefore, the culture for tuberculosis within two months after the treatment is still mandatory to consider the appropriate treatment regimen for the specific patient. However, the use of line probe assay 1st line drug or Xpert MTB/XDR is able to detect levofloxacin-resistant tuberculosis, thus helping establish the treatment regimen in the meantime. Additionally, for the pharmacokinetics and safety study of Levofloxacin in children with tuberculosis, a total of 10 children were equally divided into two groups which the first group received levofloxacin dosed 15-20 mg/kg/day which is a WHO recommendation dose in 2020 and 20-30 mg/kg/day in the second group. As a result, the serum levofloxacin level was lower than the therapeutic level in the first group and reached the therapeutic level in the second one, with no significant adverse event. Therefore, our study recommended increasing the levofloxacin dose to 20-30 mg/kg/day as the standard treatment of drug-resistant tuberculosis in children in order to enhance the therapeutic efficacy and minimize the risk of levofloxacin-resistant tuberculosis in the future.
