Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

ABSTRACT

Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment.

Areas covered: Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment.

Expert opinion: Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment.

KEYWORDS:

• Biomarkers
• dried blood spots
• drug susceptibility testing
• limited sampling
• molecular testing
• pharmacokinetics/pharmacodynamics
• therapeutic drug monitoring
• tuberculosis treatment

Article highlights

• TDM, tailoring the dose to the individual patient based on plasma concentrations, has the potential to improve therapy, but is not yet included in the treatment guidelines of TB of WHO.

• TDM should ultimately be performed by using PK/PD targets, integrating both concentration and effect of the anti-TB drug in time, but for most anti-TB drugs these are still unknown.

• Dried blood spots provide us with a more stable and patient friendly way, for the determination of plasma concentrations of anti-TB drugs as well as the diagnosis of TB, using IP-10 as a biomarker.

• Limited sampling provides us with a new less expensive and less time-consuming way to determine the AUC of anti-TB drugs.

• The rise of WGS and novel drug resistance testing methods provide opportunities to find mutations causing resistance in M. tuberculosis, that are currently still unknown.

• Measurement of the kinetics of circulating host markers has potential to monitor treatment for the detection of treatment failures.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.