ArticleFrontiers in antibiotics2026
Simultaneous measurement of 16S-rRNA and pre-16S-rRNA as a strategy to monitor clinical tuberculosis.
Article in Frontiers in antibiotics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00760149 (Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.), which is not on this map. Not yet cited in PubMed.
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Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.
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9 authors.
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Abstract
Background: Culture-based biomarkers of TB treatment response monitoring, e.g., Mycobacterial Growth Indicatory Tube (MGIT), are compromised when bacteria enter a non-replicating persister phase limiting the measurement of antibiotic efficacy and resistance. Understanding how antibiotic exposure to antibiotics alters bacterial physiology could help develop more effective TB therapies. We developed a novel assay with simultaneous measurement of 16S rRNA (bacterial burden) and its precursor, pre-16S rRNA (metabolic activity), and tested it on samples from patients in a trial of optimised-dose rifampicin. Methods: We developed a multiplex reverse transcriptase quantitative PCR assay (RT-qPCR) to measure relative gene expression of pre-16S rRNA and 16S rRNA in pre-treatment (control) and sequential samples from patients in the Phase II HIGHRIF2 (NCT00760149) clinical trial. We constructed a mathematical model to assess changes in pre-16S gene expression relative to 16S rRNA over time, facilitating the comparison of rifampicin doses' efficacy. Findings: In a retrospective study of 19 patients, pre-16S rRNA and 16S rRNA decreased steadily during the initial 36 days of treatment. This was evidenced by the rising cycle threshold (Cq) values slope 0.404 and 0.212, respectively, however, pre-16S rRNA decreased significantly quicker (P<0.0001). The changes in the relative gene expression of pre-16S rRNA during treatment fitted a double exponential decay curve (R Interpretation: The pre-16S rRNA and 16S rRNA gene expression multiplex PCR reported here provides an easy to use and rapid marker of drug efficacy and has potential to assess the efficacy of existing or novel drug combinations.
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