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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 - Yonsei Med. J. (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.

ABSTRACT

Purpose: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (C(trough)) 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 C(trough)>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 C(trough)>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.

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Related in: MedlinePlus

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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Figure 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.

Mentions: The dose-response (TAR) relationships observed are shown in Fig. 4. For each dosing regimen, the ED50, defined as a maintenance dose where 50% of TAR was achieved, was around 200 and 600 mg/day in the AUC24/MIC >125 and AUC24/MIC >345 targets, respectively. Since the logit (P=proportion of target attainment failure at day 7) meant the log (odds of target attainment failure) and the odds of target attainment failure was defined as P/(1-P), logit AUC24/MIC <345 or 125) equaled zero at the ED50 and ED50 for each target was thereafter calculated as follows:


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 - Yonsei Med. J. (2011)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104459&req=5

Figure 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.
Mentions: The dose-response (TAR) relationships observed are shown in Fig. 4. For each dosing regimen, the ED50, defined as a maintenance dose where 50% of TAR was achieved, was around 200 and 600 mg/day in the AUC24/MIC >125 and AUC24/MIC >345 targets, respectively. Since the logit (P=proportion of target attainment failure at day 7) meant the log (odds of target attainment failure) and the odds of target attainment failure was defined as P/(1-P), logit AUC24/MIC <345 or 125) equaled zero at the ED50 and ED50 for each target was thereafter calculated as follows:

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.

ABSTRACT

Purpose: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (C(trough)) 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 C(trough)>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 C(trough)>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.

Show MeSH
Related in: MedlinePlus