Nicolau David P
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102, USA.
Clin Infect Dis. 2008 Sep 15;47 Suppl 1:S32-40. doi: 10.1086/590064.
Pharmacokinetic and pharmacodynamic profiles of antibiotics are important in determining effective dosing regimens. Although minimum inhibitory concentration (MIC) data reflect microbial susceptibility to an antibiotic, they do not provide dosing information. The integration of pharmacokinetic and microbiological data, however, can be used to design rational dosing strategies. Meropenem is a broad-spectrum beta-lactam antibiotic that penetrates most body fluids and tissues rapidly after intravenous administration. Meropenem undergoes primarily renal elimination; therefore, dosage adjustment is required for patients with renal impairment. Meropenem is indicated for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and bacterial meningitis. Meropenem has time-dependent bactericidal activity; thus, the percentage of time that free-drug concentrations are higher than the MIC (%T>MIC) best characterizes the drug's pharmacodynamic profile (bactericidal target of approximately 40%T>MIC). Pharmacodynamic modeling can identify regimens with the greatest probability of attaining this target, and probabilities can be compared with clinical and microbiological responses in patients.
抗生素的药代动力学和药效学特征对于确定有效的给药方案至关重要。虽然最低抑菌浓度（MIC）数据反映了微生物对抗生素的敏感性，但它们并不能提供给药信息。然而，药代动力学和微生物学数据的整合可用于设计合理的给药策略。美罗培南是一种广谱β-内酰胺类抗生素，静脉给药后能迅速穿透大多数体液和组织。美罗培南主要经肾脏排泄；因此，肾功能不全患者需要调整剂量。美罗培南适用于治疗复杂性皮肤和皮肤结构感染、复杂性腹腔内感染及细菌性脑膜炎。美罗培南具有时间依赖性杀菌活性；因此，游离药物浓度高于MIC的时间百分比（%T>MIC）最能表征该药的药效学特征（杀菌目标约为40%T>MIC）。药效学建模可以识别最有可能达到该目标的给药方案，并且可以将概率与患者的临床和微生物学反应进行比较。
