Yonsei Med J.  2011 Jul;52(4):616-623. 10.3349/ymj.2011.52.4.616.

Teicoplanin Dosing Strategy for Treatment of Staphylococcus aureus in Korean Patients with Neutropenic Fever

• Ahn BJ
• Yim DS
• Lee DG
• Kwon JC
• Kim SH
• Choi SM

• KMID: 1727994
• DOI: http://doi.org/10.3349/ymj.2011.52.4.616

Abstract

PURPOSE
The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (Ctrough) and microorganism-specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever.
MATERIALS AND METHODS
One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis.
RESULTS
The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively.
CONCLUSION
The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.

Keyword

Teicoplanin; Staphylococcus aureus; neutropenia; pharmacokinetics; pharmacodynamics

MeSH Terms

Anti-Bacterial Agents/administration & dosage/*pharmacology/therapeutic use
Computer Simulation
Dose-Response Relationship, Drug
Fever/drug therapy/microbiology
Humans
Microbial Sensitivity Tests
Neutropenia/drug therapy/microbiology
Republic of Korea
Staphylococcal Infections/drug therapy
Staphylococcus aureus/*drug effects
Teicoplanin/administration & dosage/*pharmacology/therapeutic use
Treatment Outcome

Figure

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  Fig. 1 Summarized study flow to determine the dose-response relationship of teicoplanin against S. aureus in febrile neutropenic Korean patients. PK, pharmacokinetic; AUC, area under the curve; MIC, minimum inhibitory concentration.

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  Fig. 2 Frequency distribution of teicoplanin MIC for 78 S. aureus isolates from patients with neutropenic fever patients at the Catholic hematopoietic stem cell transplantation center, Seoul, Korea through 2005-2007. MIC, minimum inhibitory concentration.

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  Fig. 3 TARs according to several therapeutic targets with several dosing schemes during 2 weeks of teicoplanin administration; TAR for Ctrough >10 mg/L, Ctrough >20 mg/L, AUC24/MIC >125 and AUC24/MIC >345. TAR, target attainment rate; AUC, area under the curve; MIC, minimum inhibitory concentration.

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  Fig. 4 Maintenance dose - response (TAR) relationships obtained from logistic regression; ED50, defined as a maintenance dose where 50% TAR was achieved; TAR for AUC24/MIC >345 (open circle) or 125 (closed rectangle). TAR, target attainment rate; AUC, area under the curve; MIC, minimum inhibitory concentration.

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