ArticleAntimicrobial agents and chemotherapy2011
Plasma drug activity assay for treatment optimization in tuberculosis patients.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
DNA Sequencing of MDR TB in Eastern Siberia
A Randomized Clinical Trial of Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020Pooled it
- Pharmacodynamic biomarkers for quantifying the mycobacterial effect of high doses of rifampin in patients with rifampin-susceptible pulmonary tuberculosis.International journal of mycobacteriologyTrial
- Exposure to the four first-line anti-tuberculosis drugs and treatment outcomes: a target trial emulation study in Ghana.BMC infectious diseases · 2026Article
- Toward a Clinical Decision Support System for Monitoring Therapeutic Antituberculosis Medical Drugs in Tanzania (Project TuberXpert): Protocol for an Algorithm' Development and Implementation.JMIR research protocols · 2024Article
- Population Pharmacokinetics and Significant Under-Dosing of Anti-Tuberculosis Medications in People with HIV and Critical Illness.Antibiotics (Basel, Switzerland) · 2021Article
- Therapeutic Drug Monitoring: The Need for Practical Guidance.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Plasma Levels of Rifampin Correlate with the Tuberculosis Drug Activity Assay.Antimicrobial agents and chemotherapy · 2018Article
- The importance of clinical pharmacokinetic-pharmacodynamic studies in unraveling the determinants of early and late tuberculosis outcomes.International journal of pharmacokinetics · 2017Review
- Gridlock from Diagnosis to Treatment of Multidrug-Resistant Tuberculosis (MDR-TB) in Tanzania: Illuminating Potential Factors for Possible Intervention.The East African health research journal · 2017Article
- The Influence of Mining and Human Immunodeficiency Virus Infection Among Patients Admitted for Retreatment of Tuberculosis in Northern Tanzania.The American journal of tropical medicine and hygiene · 2015Article
- Improvement in plasma drug activity during the early treatment interval among Tanzanian patients with multidrug-resistant tuberculosis.PloS one · 2015Article
- Review of evidence for measuring drug concentrations of first-line antitubercular agents in adults.Clinical pharmacokinetics · 2014Review
- Understanding pharmacokinetics to improve tuberculosis treatment outcome.Expert opinion on drug metabolism & toxicology · 2014Review
- Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2014Article
- Complete genome sequence of the frog pathogen Mycobacterium ulcerans ecovar Liflandii.Journal of bacteriology · 2013Article
- Early Therapeutic Drug Monitoring for Isoniazid and Rifampin among Diabetics with Newly Diagnosed Tuberculosis in Virginia, USA.Tuberculosis research and treatment · 2013Article
- Diagnosis and interim treatment outcomes from the first cohort of multidrug-resistant tuberculosis patients in Tanzania.PloS one · 2013Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin, ethambutol, and pyrazinamide were measured at the time of typical peak plasma concentration (C(2 h)). To evaluate the significance of the effect of observed drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA) assay was developed using the Bactec MGIT system. Time to detection of plasma-cocultured M. tuberculosis versus time to detection of control growth was defined as a TDA ratio. TDA assays were later performed using the subject's own M. tuberculosis isolate and C(2 h) plasma from the Tanzanian cohort and compared to drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years ± 10.7 were enrolled. Fourteen (88%) had C(2 h) rifampin levels and 11 (69%) had isoniazid levels below 90% of the lower limit of the expected range. Plasma spiked with various concentrations of antituberculosis medications found TDA assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of isoniazid and rifampin concentrations, TDA exhibited a statistically significant correlation with drug level and drug MIC, and a TDA of ~1.0 indicated the presence of multidrug-resistant TB. In Tanzania, low (≤ 2.0) TDA was significantly associated with both lower isoniazid and rifampin C(2 h) levels, and very low (≤ 1.5) TDA corresponded to a trend toward lack of cure. Study of TDA compared to additional clinical outcomes and as a therapeutic management tool is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.