Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections

Kazuaki Matsumoto, Erika Watanabe, Naoko Kanazawa, Tomohide Fukamizu, Akari Shigemi, Yuta Yokoyama, Kazuro Ikawa, Norifumi Morikawa, Yasuo Takeda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Teicoplanin is a glycopeptide antibiotic that has been used to treat serious, invasive infections caused by Gram-positive bacteria. The area under the drug concentration–time curve (AUC)/minimum inhibitory concentration (MIC) was identified as a pharmacokinetic–pharmacodynamic (PK–PD) parameter of glycopeptide antibiotics that correlated with bacteriological responses and clinical outcomes. Although optimized dosing regimens based on PK–PD are needed, a PK–PD analysis of teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) infections has not yet been performed. Thus, this study examined patients with MRSA infections, who were administered with teicoplanin in order to determine the target AUC/MIC ratio. Methods: This study retrospectively assessed data obtained as part of our routine therapeutic drug monitoring (TDM) of teicoplanin therapy in 46 patients with MRSA infections at Kagoshima University Hospital. Serum concentrations of teicoplanin were determined using a fluorescence polarization immunoassay system and used for a Bayesian PK estimation to estimate AUC for 24 hours (AUC24). The MIC value for teicoplanin was determined using a standardized agar dilution method. The effects of teicoplanin were evaluated in terms of bacteriological responses by a quantitative assessment. Results: The estimated AUC24/MIC ratios with and without bacteriological responses were 926.6±425.2 μg⋅h/mL (n=34) and 642.2±193.9 μg⋅h/mL, respectively (n=12; P,0.05). On the basis of a logistic regression analysis, AUC24/MIC ratios of 500 μg⋅h/mL, 700 μg⋅h/mL, and 900 μg⋅h/mL gave probabilities of treatment success of 0.50, 0.72, and 0.87, respectively. Furthermore, using the Kaplan–Meier curve analysis, an AUC24/MIC ratio of ≥900 led to a significantly stronger bacteriological response than an AUC24/MIC ratio of <900. Conclusion: These results suggest that an AUC24/MIC ratio of ≥900 μg⋅h/mL is required to ensure a sufficient bacteriological response.

Original languageEnglish
Pages (from-to)15-18
Number of pages4
JournalClinical Pharmacology: Advances and Applications
Volume8
DOIs
Publication statusPublished - 2016 Mar 30
Externally publishedYes

Fingerprint

Teicoplanin
Microbial Sensitivity Tests
Methicillin-Resistant Staphylococcus aureus
Area Under Curve
Pharmacokinetics
Infection
Glycopeptides
Fluorescence Polarization Immunoassay
Anti-Bacterial Agents
Drug Monitoring
Gram-Positive Bacteria
Agar
Logistic Models
Regression Analysis
Therapeutics

Keywords

  • AUC/MIC
  • MRSA
  • PK/PD
  • Teicoplanin

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections. / Matsumoto, Kazuaki; Watanabe, Erika; Kanazawa, Naoko; Fukamizu, Tomohide; Shigemi, Akari; Yokoyama, Yuta; Ikawa, Kazuro; Morikawa, Norifumi; Takeda, Yasuo.

In: Clinical Pharmacology: Advances and Applications, Vol. 8, 30.03.2016, p. 15-18.

Research output: Contribution to journalArticle

Matsumoto, Kazuaki ; Watanabe, Erika ; Kanazawa, Naoko ; Fukamizu, Tomohide ; Shigemi, Akari ; Yokoyama, Yuta ; Ikawa, Kazuro ; Morikawa, Norifumi ; Takeda, Yasuo. / Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections. In: Clinical Pharmacology: Advances and Applications. 2016 ; Vol. 8. pp. 15-18.
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AU - Shigemi, Akari

AU - Yokoyama, Yuta

AU - Ikawa, Kazuro

AU - Morikawa, Norifumi

AU - Takeda, Yasuo

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N2 - Background: Teicoplanin is a glycopeptide antibiotic that has been used to treat serious, invasive infections caused by Gram-positive bacteria. The area under the drug concentration–time curve (AUC)/minimum inhibitory concentration (MIC) was identified as a pharmacokinetic–pharmacodynamic (PK–PD) parameter of glycopeptide antibiotics that correlated with bacteriological responses and clinical outcomes. Although optimized dosing regimens based on PK–PD are needed, a PK–PD analysis of teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) infections has not yet been performed. Thus, this study examined patients with MRSA infections, who were administered with teicoplanin in order to determine the target AUC/MIC ratio. Methods: This study retrospectively assessed data obtained as part of our routine therapeutic drug monitoring (TDM) of teicoplanin therapy in 46 patients with MRSA infections at Kagoshima University Hospital. Serum concentrations of teicoplanin were determined using a fluorescence polarization immunoassay system and used for a Bayesian PK estimation to estimate AUC for 24 hours (AUC24). The MIC value for teicoplanin was determined using a standardized agar dilution method. The effects of teicoplanin were evaluated in terms of bacteriological responses by a quantitative assessment. Results: The estimated AUC24/MIC ratios with and without bacteriological responses were 926.6±425.2 μg⋅h/mL (n=34) and 642.2±193.9 μg⋅h/mL, respectively (n=12; P,0.05). On the basis of a logistic regression analysis, AUC24/MIC ratios of 500 μg⋅h/mL, 700 μg⋅h/mL, and 900 μg⋅h/mL gave probabilities of treatment success of 0.50, 0.72, and 0.87, respectively. Furthermore, using the Kaplan–Meier curve analysis, an AUC24/MIC ratio of ≥900 led to a significantly stronger bacteriological response than an AUC24/MIC ratio of <900. Conclusion: These results suggest that an AUC24/MIC ratio of ≥900 μg⋅h/mL is required to ensure a sufficient bacteriological response.

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