Therapeutic Drug Monitoring (TDM) of Antimicrobial Agents

Shin-Woo Kim

doi:10.3947/ic.2008.40.3.133

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Kim: Therapeutic Drug Monitoring (TDM) of Antimicrobial Agents

Special Article

Infection and Chemotherapy

Infection and Chemotherapy 2008; 40(3): 133-139.

Published online: 20 June 2008

DOI: https://doi.org/10.3947/ic.2008.40.3.133

Therapeutic Drug Monitoring (TDM) of Antimicrobial Agents

Shin-Woo Kim, M.D.

Department of Internal Medicine, School of Medicine, Kyungpook National University College of Medicine, Daegu, Korea.

Correspondence: Shin-Woo Kim, M.D. Department of Internal Medicine, Kyungpook National University Hospital 50, Samduk 2-Ga, Chung-Gu, Daegu, Korea 700-721 Tel: +82-053-420-6525, Fax: +82-053-424-5542, ksw2kms@knu.ac.kr

Received 21 May 2008 Accepted 26 May 2008

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Optimal exposure of certain antimicrobials and minimization of their toxicity can be achieved by therapeutic drug monitoring (TDM) of antimicrobial agents. Vancomycin and aminoglycosides are most frequently monitored because of narrow therapeutic index and potential adverse effects. The rationale of TDM based on the individual variability in pharmacokinetics (PK) and established correlation between the concentration of the drug and its therapeutic or toxic effects. Benefits of TDM are well established with many studies, the usefulness of antimicrobial TDM for the patients with risk factors of adverse effects (nephrotoxicity and ototoxicity of aminoglycoside and vancomycin) and with treatment failure or severe infection have to be emphasized. With the recent knowledge of PK and pharmacodynamics (PD), interpretation of TDM could be performed with individual PK/PD in regarding to minimal inhibitory concentration (MIC) of specific identified organism or MIC₉₀ of suspected pathogen.

Keywords: Therapeutic drug monitoring, Antimicrobials, Vancomycin, Aminoglycosides, Pharmacokinetics, Pharmacodynamics

Figures and Tables

Fig. 1

Utility curve and concentration-effect/toxicity relationships for a theoretical drug according to Eq (E=E_max·C^s/(C^s+EC₅₀^s). EC₅₀ for efficacy=10 mg/L, EC₅₀ for toxicity=60 mg/L, thus the therapeutic index is 6; s=1.0 (7).

Fig. 2

Schematic diagram of attaining steady state concentration of a certain drug. The time required to reach steady state is approximately 4-5 half-lives. Time to steady state is independent of dosage.

Fig. 3

Once-daily aminoglycoside nomogram for the assessment of dosing interval using a 7 mg/kg dose of gentamicin or tobramycin (45).

Table 1

Therapeutic Ranges of Selected Antimicrobials

OD, once daily dosing; MDD, multiple daily dosing

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