Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections
Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections
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DOI：
10.1016/j.cll.2004.03.009
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发表时间：
2004-06-01
影响因子：
1.7
通讯作者：
Craig, WA
中科院分区：
文献类型：
--
作者：
Andes, D;Anon, J;Craig, WA
研究抗菌药物药代动力学和药效学（PK/PD）的药理学领域对许多抗生素的选择和给药方案产生了重大影响，特别是那些用于治疗呼吸道感染的抗生素。鉴于抗菌素耐药性的增加，PK/PD参数尤其重要。药物药代动力学特征，如随时间变化的血清浓度和浓度-时间曲线下面积，当与抗生素对病原体的最小抑菌浓度（MIC）值相结合时，可以预测细菌根除和临床成功的概率。这些药代动力学和药效学关系在防止耐药菌株的选择和传播方面也很重要，并导致了突变预防浓度的描述，这是防止从高细菌接种物中选择耐药细菌的最低抗菌剂浓度。β-内酰胺类药物是时间依赖性药物，没有显著的抗生素后效应，当未结合的血清浓度超过这些药物对感染病原体的MIC>40%至50%的给药间隔时，导致细菌根除。大环内酯类、氮杂内酯类和林可酰胺类药物是时间依赖性药物，具有延长的抗生素后效应，氟喹诺酮类药物是浓度依赖性药物，当未结合血清曲线下面积与MIC比值超过25至30时，这两种药物均可根除细菌。这些观察结果导致针对呼吸道病原体的推荐抗菌剂剂量发生变化，并用于评估当前药物的作用，开发新制剂，并评估新抗菌剂的效力。
The pharmacologic field that studies antimicrobial pharmacokinetics and pharmacodynamics (PK/PD) has had a major impact on the choice and dosing regimens used for many antibiotics especially those used in the treatment of respiratory tract infections. PK/PD parameters are particularly important in light of increasing antimicrobial resistance. Drug pharmacokinetic features, such as serum concentrations over time and area under the concentration-time curve, when integrated with minimum inhibitory concentration (MIC) values of antibiotics against pathogens, can predict the probability of bacterial eradication and clinical success. These pharmacokinetic and pharmacodynamic relationships also are important in preventing the selection and spread of resistant strains and have led to the description of the mutation prevention concentration, which is the lowest concentration of antimicrobial that prevents selection of resistant bacteria from high bacterial inocula. beta-lactams are time-dependent agents without significant post-anti-biotic effects, resulting in bacterial eradication when unbound serum concentrations exceed MICs of these agents against infecting pathogens for >40% to 50% of the dosing interval. Macrolides, azaolides, and lincosamides are time-dependent agents with prolonged post-antibiotic effects, and fluoroquinolones are concentration-dependent agents, resulting in both cases in bacterial eradication when unbound serum area-under-the-curve to MIC ratios exceed 25 to 30. These observations have led to changes in recommended antimicrobial dosing against respiratory pathogens and are used to assess the role of current agents, develop new formulations, and assess potency of new antimicrobials.