Low Plasma Rifampicin and Isoniazid Concentration in Pulmonary TB Converters: The Importance of Antibacterial Minimal Inhibitory Concentration (A Preliminary Study)

Dedi Suyanto; Purwantyastuti Ascobat; Melva Louisa; Prayudi Santoso; Yulianti Hadi Soebroto

Dedi Suyanto Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Central Jakarta, Postal Code 10430, Indonesia
Purwantyastuti Ascobat Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Central Jakarta, Postal Code 10430, Indonesia
Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Central Jakarta, Postal Code 10430, Indonesia
Prayudi Santoso Dr. Hasan Sadikin General Hospital/Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Postal Code 40161, Indonesia
Yulianti Hadi Soebroto Bandung Lung Clinic, Ministry of Health Indonesia, Bandung, Postal Code 40241, Indonesia

Keywords: Cmax/MIC, Isoniazid, Plasma drug concentration, Pulmonary tuberculosis, Regional MIC, Rifampicin

Abstract

Background: Low plasma drug concentrations in patients with pulmonary tuberculosis (TB) may contribute to sputum conversion failure. However, previous studies have reported inconsistent findings, possibly due to regional differences in the minimum inhibitory concentration (MIC) of rifampicin and isoniazid against Mycobacterium tuberculosis (MTB). This study assessed the association between plasma drug concentrations and sputum conversion by considering regional MIC values.

Method: A case-control study involving 40 patients was conducted at four pulmonary TB facilities in Bandung, Indonesia, from January to September 2021. Participants were divided into a non-conversion group (cases, n = 20) and a conversion group (controls, n = 20). Peak plasma concentrations of rifampicin and isoniazid were measured two hours after oral administration at the end of the intensive phase using liquid chromatography–tandem mass spectrometry (LC-MS/MS).

Results: In the non-conversion group, the mean rifampicin concentration was 5.30 ± 1.71 mg/L, and the median isoniazid concentration was 1.18 mg/L (0.51–3.71). In the conversion group, the mean rifampicin concentration was 5.85 ± 2.97 mg/L, and the median isoniazid concentration was 1.81 mg/L (0.40–6.10). Isoniazid concentrations differed significantly between groups, although both drugs showed below-reference concentrations in both groups.

Conclusion: Based on conventional reference concentrations, plasma rifampicin and isoniazid concentrations were not significantly associated with sputum conversion. However, when regional MIC values were considered, the conversion group tended to have higher Cmax/MIC ratios for both drugs than the non-conversion group.