Hyatt J M, McKinnon P S, Zimmer G S, Schentag J J
Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York, USA.
Clin Pharmacokinet. 1995 Feb;28(2):143-60. doi: 10.2165/00003088-199528020-00005.
Pharmacokinetic/pharmacodynamic surrogate relationships have been used to describe the antibacterial activity of various classes of antimicrobial agents. Studies that have evaluated these relationships were reviewed to determine which of these surrogate markers were further dependent on antimicrobial class. The fluoroquinolone and aminoglycoside agents exhibit concentration-dependent killing. Studies have demonstrated that peak serum concentration: minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC): MIC ratios are important predictors of outcome for these antimicrobial agents. Area under the inhibitory concentration-time curve (AUIC24) [i.e. AUC24/MIC] is a useful parameter for describing efficacy for these agents, while an adequate peak concentration: MIC ratio seems necessary to prevent selection of resistant organisms. For beta-lactam antibiotics, the duration of time that the serum concentration exceeds the MIC (T > MIC) was the significant pharmacokinetic/pharmacodynamic surrogate in cases where the bacterial inoculum was low, or where very sensitive organisms were tested. However, in studies using more resistant organisms or larger inoculum sizes there is some concentration-dependence to the observed effect. Studies using reasonable dosage intervals have demonstrated covariance between T > MIC and AUC/MIC ratio for beta-lactam antibiotics. Since glycopeptide antibiotics display relatively slow but concentration-independent killing, and are cell wall active agents similar to beta-lactams, it has been presumed that T > MIC is the important pharmacokinetic surrogate related to efficacy for these agents. Some studies have shown that a concentration multiple of the MIC may be necessary for successful outcome with vancomycin. AUIC24 may prove to be an important pharmacokinetic surrogate if both time and concentration are indeed important parameters. To select an appropriate antimicrobial agent, the clinician must consider many patient-specific as well as organism-specific factors. Utilisation of known pharmacokinetic/pharmacodynamic surrogate relationships should help to optimise treatment outcome.
药代动力学/药效学替代关系已被用于描述各类抗菌药物的抗菌活性。对评估这些关系的研究进行了综述，以确定哪些替代标志物进一步依赖于抗菌药物类别。氟喹诺酮类和氨基糖苷类药物表现出浓度依赖性杀菌作用。研究表明，血清峰值浓度与最低抑菌浓度（MIC）之比以及血清浓度-时间曲线下面积（AUC）与MIC之比是这些抗菌药物治疗效果的重要预测指标。抑菌浓度-时间曲线下面积（AUIC24）[即AUC24/MIC]是描述这些药物疗效的一个有用参数，而适当的峰值浓度与MIC之比似乎是防止耐药菌产生的必要条件。对于β-内酰胺类抗生素，在细菌接种量低或测试非常敏感的微生物的情况下，血清浓度超过MIC的持续时间（T＞MIC）是重要的药代动力学/药效学替代指标。然而，在使用耐药性更强的微生物或更大接种量的研究中，观察到的效应存在一定的浓度依赖性。使用合理给药间隔的研究表明，β-内酰胺类抗生素的T＞MIC与AUC/MIC之比之间存在协方差。由于糖肽类抗生素表现出相对缓慢但浓度无关的杀菌作用，并且是与β-内酰胺类类似的细胞壁活性剂，因此推测T＞MIC是与这些药物疗效相关的重要药代动力学替代指标。一些研究表明，使用万古霉素成功治疗可能需要MIC的一定浓度倍数。如果时间和浓度确实都是重要参数，AUIC24可能被证明是一个重要的药代动力学替代指标。为了选择合适的抗菌药物，临床医生必须考虑许多患者特异性以及微生物特异性因素。利用已知的药代动力学/药效学替代关系应有助于优化治疗效果。
