Has the Time Come for Systematic Therapeutic Drug Monitoring of First-Line and WHO Group A Antituberculosis Drugs?

Tuberculosis (TB) is a major global health issue, with approximately 10 million people being infected each year, and is the leading cause of mortality from infectious disease, with 1.5 million deaths a year. Optimal TB treatment requires a combination of drugs for an adequate treatment duration owing to persistent organisms, hardly accessible infection sites, and a high risk of resistance selection. Long-term therapy increases the risk of patients' loss of adherence, adverse drug reactions, and drug-drug interactions, potentially leading to treatment failure. The high interpatient variability of TB drug exposure is another point eliciting interest in therapeutic drug monitoring (TDM) to optimize treatment. Studies reporting clinically relevant exposure thresholds, which might be proposed as targets toward treatment personalization, are discussed. Practical TDM strategies have also been reported to circumvent issues related to delayed drug absorption and the need for multiple samples when evaluating the area under the curve of drug concentrations. The need for treatment individualization is further emphasized because of the development of multidrug-resistant TB or extensively drug-resistant TB. Finally, the willingness to shorten the treatment duration while maintaining success is also a driver for ensuring adequate exposure to TB drugs with TDM. The aim of the present review was to underline the role of TDM in drug-susceptible TB and World Health Organization group A TB drugs.