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长期使用万古霉素发生耳毒性的风险较低。

Long-term vancomycin use had low risk of ototoxicity.

机构信息

University of Tennessee Graduate School of Medicine, Knoxville, Tennessee, United States of America.

University of Tennessee Health Sciences Center, Knoxville, Tennessee, United States of America.

出版信息

PLoS One. 2019 Nov 6;14(11):e0224561. doi: 10.1371/journal.pone.0224561. eCollection 2019.

Abstract

BACKGROUND

Vancomycin is a commonly used antibiotic with potent activity against Gram-positive organisms, but prolonged use and high doses can lead to toxicity. While vancomycin-associated nephrotoxicity is widely reported, few cases of ototoxicity have been described. The objective of this study was to determine the prevalence of negative changes in audiograms in patients receiving long-term intravenous (IV) vancomycin and to identify high-risk patients who need audiogram monitoring.

METHODS

This was an IRB approved, cross-sectional study performed at an academic medical center from 1/2012-3/2019. Patients who were prescribed IV vancomycin for ≥ 14 days and had baseline and follow-up weekly audiometry were included. All data was extracted from the electronic medical record. The primary endpoint was worsening audiogram while on vancomycin. Descriptive and bivariate statistics were used to describe the patient population.

RESULTS

424 patients were screened for inclusion; 92 received at least two audiograms while on vancomycin. Fifty-three percent of patients were men, the median (IQR) patient age was 44 (34-58) years, and 8% of patients had an estimated Cockcroft-Gault creatinine clearance ≤ 30 mL/min or received hemodialysis. The median (IQR) vancomycin exposure up until the last recorded audiogram was 30 (17-42) days. Vancomycin indications were: 53 (58%) bone and joint infections, 17 (18%) infective endocarditis, 10 (11%) bacteremia, 12 (13%) other infections. Seven (8%) patients experienced a worsening change in hearing from baseline, two (2%) of them suffered mild loss, two (2%) had mild to moderate loss, and three (3%) developed moderate-to-severe hearing loss. In bivariate analyses, no variables were found to be associated with a worsening change in audiogram, including baseline abnormal audiogram, age ≥ 40 years, elevated serum vancomycin levels, or vancomycin doses ≥ 4 grams/day.

CONCLUSIONS

The prevalence of negative changes in audiograms among patients receiving long-term intravenous vancomycin was low. The utility of routine audiogram testing in this population remains questionable except in high-risk patients; however, larger prospective studies with controls may be warranted to further explore the risk of ototoxicity.

摘要

背景

万古霉素是一种常用于治疗革兰氏阳性菌感染的抗生素,具有很强的抗菌活性,但长期使用和高剂量使用可能会导致毒性。虽然万古霉素相关性肾毒性已被广泛报道,但耳毒性的病例却很少见。本研究的目的是确定长期接受静脉注射(IV)万古霉素治疗的患者听力图出现阴性变化的发生率,并确定需要进行听力图监测的高危患者。

方法

这是一项在学术医疗中心进行的经机构审查委员会批准的横断面研究,时间为 2012 年 1 月至 2019 年 3 月。纳入接受 IV 万古霉素治疗≥14 天且有基线和每周随访听力图的患者。所有数据均从电子病历中提取。主要终点是在使用万古霉素期间听力图恶化。使用描述性和双变量统计方法描述患者人群。

结果

筛选出 424 名患者进行纳入研究,92 名患者在使用万古霉素期间至少进行了两次听力图检查。53%的患者为男性,中位(IQR)年龄为 44(34-58)岁,8%的患者估计 Cockcroft-Gault 肌酐清除率≤30ml/min或接受血液透析。直到最后一次记录听力图为止,中位(IQR)万古霉素暴露时间为 30(17-42)天。万古霉素的适应证为:53(58%)骨骼和关节感染、17(18%)感染性心内膜炎、10(11%)菌血症、12(13%)其他感染。7(8%)名患者的听力从基线开始出现恶化,其中 2(2%)名患者出现轻度听力损失,2(2%)名患者出现轻度至中度听力损失,3(3%)名患者出现中度至重度听力损失。在双变量分析中,未发现任何变量与听力图恶化相关,包括基线异常听力图、年龄≥40 岁、血清万古霉素水平升高或万古霉素剂量≥4g/天。

结论

长期接受静脉注射万古霉素治疗的患者听力图出现阴性变化的发生率较低。除高危患者外,常规听力图检查在该人群中的应用仍存在疑问;然而,可能需要更大规模的前瞻性研究来进一步探讨耳毒性的风险。

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