Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems

ABSTRACT

Introduction

Therapeutic drug monitoring (TDM) has been recommended for treatment optimization in tuberculosis (TB) but is only is used in certain countries e.g. USA, Germany, the Netherlands, Sweden and Tanzania. Recently, new drugs have emerged and PK studies in TB are continuing, which contributes further evidence for TDM in TB. The aim of this review is to provide an update on drugs used in TB, treatment strategies for these drugs, and TDM to support broader implementation.

Areas covered

This review describes the different drug classes used for TB, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), along with their pharmacokinetics, dosing strategies, TDM and sampling strategies. Moreover, the review discusses TDM for patient TB and renal or liver impairment, patients co-infected with HIV or hepatitis, and special patient populations – children and pregnant women.

Expert opinion

TB treatment has a long history of using ‘one size fits all.’ This has contributed to treatment failures, treatment relapses, and the selection of drug-resistant isolates. While challenging in resource-limited circumstances, TDM offers the clinician the opportunity to individualize and optimize treatment early in treatment. This approach may help to refine treatment and thereby reduce adverse effects and poor treatment outcomes. Funding, training, and randomized controlled trials are needed to advance the use of TDM for patients with TB.

KEYWORDS:

• Therapeutic drug monitoring
• tuberculosis
• mdr-TB
• pharmacokinetics
• pharmacodynamics

Article highlights

• TDM could have an important role in prevention of acquired drug resistance associated with low exposure.

• Pharmacokinetic/pharmacodynamic considerations could help clinicians select the right dose for optimization of therapy.

• Implementing optimal sampling strategies strategies for TDM will be a game changer in implementation of precision dosing.

• Special consideration needs to be given to vulnerable subpopulations – e.g. children, HIV positive/diabetic patients and during renal and hepatic impairment.

• TDM will only be beneficial if sufficient access and short turn around time can be guaranteed at community, regional and central level.

This box summarizes key points contained in the article.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Anne-Grete Märtson was supported by the Foundation ‘De Drie Lichten’ in The Netherlands and was funded by Marie Skłodowska-Curie Actions [grant agreement no. 713660— PRONKJEWAIL—H2020-MSCA-COFUND-2015].