Bertino J S, Rodvold K A, Destache C J
Department of Pharmacy Services, Mary Imogene Bassett Hospital, Cooperstown, New York.
Clin Pharmacokinet. 1994 Jan;26(1):71-81. doi: 10.2165/00003088-199426010-00006.
Aminoglycoside antibiotics are very important in the treatment of Gram-negative infections and as synergistic agents for the treatment of staphylococcal and streptococcal (group B streptococci and enterococci) infections. However, these agents have a narrow therapeutic index. Thus, a number of new antibiotics have been introduced in an attempt to reduce the number of patients treated with aminoglycosides. Unfortunately, these new antibiotics tend to be costly, and are often associated with development of resistance and treatment failure. Data suggest that a pharmacokinetic/pharmacodynamic relationship exists for some aspects of efficacy and toxicity of aminoglycosides. Serum drug concentrations and/or tissue accumulation are related to the development of nephrotoxicity, and individualised pharmacokinetic monitoring may decrease rates of nephrotoxicity. Peak serum drug concentrations and the ratio of peak serum drug concentration to minimum inhibitory concentration appear to correlate with clinical efficacy in the treatment of patients with bacteraemia or pneumonia. Therapeutic drug monitoring (TDM) has been used to optimise aminoglycoside therapy and reduce toxicity. Cost-effective approaches to drug selection and TDM are important considerations in the proper use of aminoglycosides.
氨基糖苷类抗生素在治疗革兰氏阴性菌感染以及作为治疗葡萄球菌和链球菌(B组链球菌和肠球菌)感染的协同剂方面非常重要。然而,这些药物的治疗指数较窄。因此,人们引入了一些新抗生素,试图减少使用氨基糖苷类药物治疗的患者数量。不幸的是,这些新抗生素往往价格昂贵,并且常常与耐药性的产生和治疗失败有关。数据表明,氨基糖苷类药物的疗效和毒性的某些方面存在药代动力学/药效学关系。血清药物浓度和/或组织蓄积与肾毒性的发生有关,个体化的药代动力学监测可能会降低肾毒性发生率。血清药物峰浓度以及血清药物峰浓度与最低抑菌浓度的比值似乎与菌血症或肺炎患者治疗中的临床疗效相关。治疗药物监测(TDM)已被用于优化氨基糖苷类药物治疗并降低毒性。在合理使用氨基糖苷类药物时,具有成本效益的药物选择和TDM方法是重要的考虑因素。