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万古霉素的耳毒性和肾毒性。综述。

Vancomycin ototoxicity and nephrotoxicity. A review.

作者信息

Bailie G R, Neal D

机构信息

University of Manchester, Department of Pharmacy, Hope Hospital, Salford, England.

出版信息

Med Toxicol Adverse Drug Exp. 1988 Sep-Oct;3(5):376-86. doi: 10.1007/BF03259891.

Abstract

Vancomycin has been in clinical use as a potent antistaphylococcal antibiotic for over 30 years. Most reports of ototoxicity and nephrotoxicity have been associated with early, relatively impure, formulations of vancomycin. This paper reviews the literature concerning vancomycin ototoxocity and nephrotoxicity and the evidence for their correlation with the therapeutic serum concentration range. There have been 28 reports of vancomycin-associated ototoxicity published in the medical literature since 1958. It remains unclear whether any diminution in hearing is permanent or reversible. Few patients in the literature had follow-up audiometry and the hearing impairment tends to be at higher frequencies. Several authors reported peak serum vancomycin concentrations, but the exact time these were drawn with respect to the last dose is mostly unclear. In other reports, the 'peak' concentrations noted 3 to 6 hours after the last dose are probably indicative of much higher concentrations because of vancomycin's rapid phase of distribution. More than half the 57 cases of reported nephrotoxicity due to vancomycin occurred within the first 6 years of the drug's use. Many of these patients also had pre-existing renal dysfunction or were concomitantly receiving other nephrotoxic agents. It is unclear whether the coadministration of aminoglycosides produces a synergistic toxicity. The exact incidence of nephrotoxicity is uncertain, but is probably less with the current, relatively pure, product. The correlation of nephrotoxicity with certain serum vancomycin concentrations remains to be clarified. Other aspects also require clarification, such as when to draw samples to determine peak serum concentrations and whether or not routine measurements are necessary at all. In the absence of better guidelines, efforts should be made to tailor individual patient's regimens to produce peak and trough serum vancomycin concentrations to within the widely accepted ranges of 30 to 40 and 5 to 10 mg/L, respectively. In addition, the concomitant use of other potentially nephrotoxic and ototoxic agents should be avoided.

摘要

万古霉素作为一种强效抗葡萄球菌抗生素已在临床使用超过30年。大多数关于耳毒性和肾毒性的报告都与早期相对不纯的万古霉素制剂有关。本文综述了有关万古霉素耳毒性和肾毒性及其与治疗性血清浓度范围相关性的文献。自1958年以来,医学文献中已发表了28篇关于万古霉素相关耳毒性的报告。目前尚不清楚听力下降是否是永久性的还是可逆的。文献中很少有患者进行随访听力测定,且听力损害往往发生在较高频率。几位作者报告了血清万古霉素峰值浓度,但这些浓度相对于最后一剂的确切采血时间大多不清楚。在其他报告中,最后一剂后3至6小时记录的“峰值”浓度可能由于万古霉素快速分布阶段而指示更高的浓度。在报告的57例因万古霉素导致的肾毒性病例中,超过一半发生在该药物使用的头6年内。这些患者中的许多人还存在既往肾功能不全或同时接受其他肾毒性药物治疗。尚不清楚氨基糖苷类药物的联合使用是否会产生协同毒性。肾毒性的确切发生率尚不确定,但使用目前相对纯的产品时可能较低。肾毒性与某些血清万古霉素浓度的相关性仍有待阐明。其他方面也需要澄清,例如何时采集样本以确定血清峰值浓度以及是否根本需要常规测量。在缺乏更好指导原则的情况下,应努力调整个体患者的用药方案,以使血清万古霉素峰值和谷值浓度分别保持在30至40毫克/升和5至10毫克/升这一广泛接受的范围内。此外,应避免同时使用其他潜在的肾毒性和耳毒性药物。

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