ABSTRACT
Background: The prevalence of drug-resistant tuberculosis (DR-TB) in adults has stabilized in the past decade. Our study aimed to describe the prevalence of DR-TB in Thai children between 2006 and 2021. Materials and methods: Children younger than 15 years old who had culture-confirmed Mycobacterium tuberculosis complex (MTB), positive PCR-MTB, or positive Xpert MTB/RIF were included in this cohort. Drug susceptibility testing (DST) was performed using phenotypic and/or genotypic methods. The prevalence of DR-TB was compared using the chi-square test. Results: Among 163 confirmed TB cases (44% as pulmonary TB, 27% as extrapulmonary TB, and 29% with both), the median age (IQR) was 12.2 (7.3-14.2) years. DST was performed in 139 cases (85%), revealing prevalences of all DR-TB, isoniazid-resistant TB (Hr-TB), and rifampicin monoresistant/multidrug-resistant TB (Rr/MDR-TB) of 21.6% (95% CI 14.7-28.4), 10.8% (95% CI 5.6-16.0%), and 2.9% (95% CI 0.1-5.7%), respectively. The DR-TB rates did not differ significantly between 2006-2013, 2014-2018, and 2019-2021 (p > 0.05). Two pre-extensively DR-TB (pre-XDR) cases with fluoroquinolone resistance were detected after 2014. Conclusion: The prevalence of DR-TB in Thai children was stable. However, one-tenth of DR-TB cases confirmed with DST were Hr-TB, which required adjustment of the treatment regimen. The pre-XDR cases should be closely monitored.
ABSTRACT
OBJECTIVES: To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage. METHODS: Children aged 1-15 years with tuberculosis who received levofloxacin-based treatment for at least 7 days were enrolled. First, five children were enrolled to receive the WHO-recommended dosage (15-20 mg/kg/day), then an additional five children received a dosage higher than the WHO-recommended dosage (20-30 mg/kg/day). Blood samples were collected at predose and postdose 1, 2, 4, 6, 8, and 12 hours. A target of the ratio of the free area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was 100. RESULTS: The median (interquartile range) age was 9.6 (4.9-10.5) and 12.0 (10.1-12.3) years in the WHO dosage and higher-than-WHO dosage groups, respectively. The median (interquartile range) duration of antituberculosis treatment was 24 (8-24) weeks. The geometric mean (95% confidence interval) of fAUC/MIC was 60.4 (43.5-84.0) and 103.2 (70.1-151.8) in the WHO and higher-than-WHO dosage groups, respectively. There was no adverse event of QT prolongation or any other grade 3 or 4 adverse events. CONCLUSION: Levofloxacin at a higher dose of 20-30 mg/kg/day could achieve the fAUC/MIC target in children.
