The Role of Therapeutic Drug Monitoring in Mycobacterial Infections

Abstract

Tuberculosis (TB) is a leading cause of infectious death. Nontuberculous mycobacteria (NTM) cause a wide variety of difficult-to-treat infections in various human hosts. Therapeutic drug monitoring (TDM) remains a standard clinical technique that uses plasma drug concentrations to determine dose. The reason to do this is simple: drug exposure (that is, the free drug area under the plasma concentration-time curve) relative to the MIC and not the dose per se largely determines the outcome of the infections. TDM provides objective information that clinician can use to make informed dosing decisions. The normal plasma concentration ranges provide reasonable guidance for initial target concentrations. Clinicians then combine concentration data with knowledge about the patients, in order to decide how aggressive to be with dosing. With sicker patients, who are closer to a poor outcome, one may be willing to accept an increased risk of potential toxicity in order to secure patient survival. In the clinic, time and resources are limited, so typically only two samples are collected postdose. The 2-h postdose concentrations approach the peak for most TB and NTM drugs. A 6-h sample allows the clinician to distinguish between delayed absorption and malabsorption, because patients with the latter need higher doses in order to gain the benefit associated with standard doses. Plasma concentrations do not account for all of the variability in patient responses to TB or NTM treatment, and concentrations cannot guarantee patient outcomes. However, combined with clinical and bacteriological data, TDM can be a decisive tool, allowing clinicians to look inside of their patients and adjust doses based on objective data. Knowing the dose, rather than guessing at the dose, is the path to shorter and more successful treatment regimens.

FIGURE 1

CDC slide showing that 88% of U.S. TB patients complete treatment at 12 months, not 6 months.