Pharmacokinetics/Pharmacodynamicsに基づくVancomycin投与設計の有用性

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  • Evaluation of the usefulness of vancomycin dosage design based on pharmacokinetics/pharmacodynamics theory

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We analyzed 79 patients administered vancomycin hydrochloride (Vancomycin: VCM) to treat methicillinresistant Staphylococcus aureus (MRSA) from April 2003 through March 2006. In Pharmacokinetics/Pharmacodynamics (PK/PD) theory, the ratio of the area under the concentration-time curve over 24 hours to the minimum inhibitory concentration (AUC24/MIC) of VCM is related to clinical outcome. According to MIC distributions for VCM against MRSA in this study, MICs in the non-treated group of patients with VCM were 1.0μg/mL, whereas nearly half of the patients treated group with VCM showed MIC of 2.0μg/mL. Among those treated with VCM, the respiratory tract, a difficult-to-reach site for VCM, accounted for 46.8% of all infection sites. In PK/PD theory, these results indicate that patients may possibly be difficult to treat. In fact, effectiveness was 51.6%(16/31) in non-TDM patients and 75.0%(36/48) in TDM patients. Despite its apparent usefulness, 35.4%(17/48) of TDM patients whose dosage was not adjusted based on PK/PD theory did not achieve sufficient blood levels, suggesting the possibility of poor therapeutic outcome. In TDM of VCM, dosage adjustment based on PK/PD theory thus appears vital to ensure safety and enhanced effectiveness. Serum albumin analyzed between successful and unsuccessful cases in patients treated with VCM therapy was significantly lower in unsuccessful than successful cases (p<0.01). To achieve better therapeutic outcome, both treatment with antimicrobial agents and nutritional support thus appear necessary.

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