Abstract
BackgroundLow plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages.MethodsChildren with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method.ResultsIn all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (≤ 2 years, 2–12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range.ConclusionsBased on our findings, monitoring patients’ drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.
Highlights
Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients
Treatment regimen and side effects in children with active and latent TB Children with active TB were 19/45 (42.2%), of which 17/19 (89.5%) were treated with a four-drug regimen comprised of INH, RIF, pyrazinamide (PZN) and
(1) Definite TB: children with Mycobacterium tuberculosis cultured or detected by microscopy or molecular methods from gastric aspirate culture or sputum; (2) Probable TB: absence of microbiological confirmation but presence of the following criteria: abnormal radiography and/or computed tomography scan consistent with lung TB, positive clinical response to TB therapy, clinical signs and symptoms of active TB, and either a history of TB contact or travel to a TB-endemic country within the last 24 months [21]
Summary
Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. A large inter-patient variability of plasma levels of isoniazid (INH), with plasma concentrations frequently below the expected therapeutic range has been observed in most studies [5,6,7]. Low plasma levels of first-line antitubercular drugs can be counted as being among the main causes of poor response to therapy. A delayed or insufficient treatment response can lead to prolonged therapy, and to the development of resistant strains or possible relapses of the disease [8, 9]
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