https://doi.org/10.4081/monaldi.2024.3036
Study of risk factors and clinical management of patients with clinical non-response due to low plasma levels of anti-tubercular drugs
Submitted: April 28, 2024
Accepted: May 3, 2024
Published: July 23, 2024
Accepted: May 3, 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
This study was carried out to assess the role of therapeutic drug monitoring of crucial first-line anti-tubercular drugs: rifampicin (R) and isoniazid (H) among 75 non-responding proven drug-sensitive tuberculosis patients on treatment followed by intervention in field conditions. The intervention was done in the form of either an increase in the dosage of R and H in patients with minimally low drug levels or a modification of the regimen in a certain group of patients with significantly low drug levels by augmenting it with three or four second-line drugs in addition to standard first-line drugs. This study also aimed to determine the relationship between the measured plasma concentration of anti-tubercular drugs and various demographic, microbiological, radiological, and malabsorption factors and the presence of co-morbidities affecting them. The study also focused on the clinical impact of the intervention for low plasma levels of anti-TB drugs on TB treatment outcomes. In our study overall, 85.5% of patients had low levels of any drug. In 85.3% of patients, R levels were low, and in 39.1%, H levels were low. On univariate analysis, low body mass index (BMI), hypoalbuminemia, bilateral disease on chest X-rays, and the presence of cavities were found to be significantly associated with low drug levels, while none of the factors were independently significantly associated. Low BMI, pulmonary tuberculosis and disseminated tuberculosis, far-advanced disease and bilateral disease on chest X-ray, presence of cavities, and only low R levels were associated with unfavorable outcomes, with none of the factors found to be significant on multivariate analysis. In our study, it was seen that the treatment outcome was favorable in 59.6% of patients in whom this intervention was done by augmenting the treatment regimen with three/four second-line drugs along with increasing the dose of R and H. To conclude, various factors may be associated with low plasma levels of anti-tubercular drugs. If such patients show clinical non-response after >6 months of treatment and have significantly low drug levels, with an absence of drug resistance, their treatment regimen may need augmentation with three/four second-line drugs along with an increase in the dose of R and H, which may lead to a favorable outcome.
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Ethics Approval
Research and ethical approval (office letter no. NITRD/RC/2024/2521, letter no. NITRD/EC/2024/7497 respectively) has been obtained from Institutional Research and Ethical Committee.How to Cite
Singla, Rupak, Amitesh Gupta, Vikas Kumar, Chandrasekaran Padmapriyadarsini, Devika Tayal, Shweta Anand, Abhishek Faye, AK Hemanth Kumar, and Madhumita Paul Choudhary. 2024. “Study of Risk Factors and Clinical Management of Patients With Clinical Non-Response Due to Low Plasma Levels of Anti-Tubercular Drugs”. Monaldi Archives for Chest Disease, July. https://doi.org/10.4081/monaldi.2024.3036.
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