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The Role of Therapeutic Drug Monitoring in Mycobacterial Infections

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  • Author: Charles Peloquin1
  • Editor: David Schlossberg2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Infectious Disease Pharmacokinetics Lab, College of Pharmacy, Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610; 2: Philadelphia Health Department, Philadelphia, PA
  • Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TNMI7-0029-2016
  • Received 16 November 2016 Accepted 17 November 2016 Published 13 January 2017
  • Charles Peloquin, peloquin@cop.ufl.edu
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  • 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 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.

  • Citation: Peloquin C. 2017. The Role of Therapeutic Drug Monitoring in Mycobacterial Infections. Microbiol Spectrum 5(1):TNMI7-0029-2016. doi:10.1128/microbiolspec.TNMI7-0029-2016.

Key Concept Ranking

Infectious Diseases
0.6881658
Antibiotics
0.57459235
Gastrointestinal Diseases
0.57192844
Antimicrobials
0.5099426
Diagnosis
0.5012256
Haemophilus influenzae
0.46974623
0.6881658

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2017-01-13
2017-08-20

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 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.

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Figures

Image of FIGURE 1
FIGURE 1

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

Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TNMI7-0029-2016
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Tables

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TABLE 1

Patients who especially may benefit from TDM

Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TNMI7-0029-2016
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TABLE 2

Pharmacokinetic parameters of the anti-TB drugs

Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.TNMI7-0029-2016

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