庆大霉素雾化吸入,临床用途和不良反应知多少?

2018-06-02 张药师 药评中心

庆大霉素是临床常用的氨基糖苷类抗生素。动物实验和大量临床报道已证明庆大霉素注射液有较强的耳毒性和肾毒性。目前,临床肌肉注射和静脉滴注主要用于严重感染,而且日趋合理,但滥用庆大霉素注射液进行雾化吸入的问题比较严重。


庆大霉素是临床常用的氨基糖苷类抗生素。动物实验和大量临床报道已证明庆大霉素注射液有较强的耳毒性和肾毒性。目前,临床肌肉注射和静脉滴注主要用于严重感染,而且日趋合理,但滥用庆大霉素注射液进行雾化吸入的问题比较严重。

一、国外和国内雾化吸入的适应症

氨基糖苷类主要给药途径是肌肉注射和静脉滴注,常与其它抗菌药(β-内酰胺类,万古霉素,甲硝唑)联用以扩大其抗菌谱或增强抗菌活性,用于严重感染的治疗。氨基糖苷类也可口服治疗肠道感染,但胃肠疾病(溃疡、肠炎)时,氨基糖苷类吸收增加,可达到毒性血药浓度。

1、国外雾化吸入的适应症

国外雾化吸入主要用于慢性铜绿假单胞菌肺部感染的囊性纤维化(CF)患者和非CF性慢性支气管扩张患者。常用的药物有妥布霉素吸入溶液(国外已批准上市)、阿米卡星注射液和庆大霉素注射液。

氨基糖苷类雾化吸入主要原因是氨基糖苷类药物很难进入炎症组织,雾化吸入可以确保其在感染部位的高浓度,并减少全身毒性。对已上市的妥布霉素吸入溶液的研究表明,雾化吸入后痰中药物浓度高,而血液中的药物浓度很低。

目前FDA只批准妥布霉素吸入液用于囊性纤维化患者,国外正在研发的雾化吸入制剂有庆大霉素亮氨酸干粉吸入剂。

2、国内雾化吸入的适应症

国内无批准上市的氨基糖苷类雾化吸入制剂,临床常用庆大霉素注射液治疗咽炎、支气管炎、扁桃体炎、肺炎等呼吸道感染。但目前为止,尚不能充分证实庆大霉素注射液雾化吸入治疗上述感染的有效性和安全性。

氨基糖苷类抗生素对需氧G-菌有较强的抗菌活性,但对多数G+菌的活性很弱,对厌氧菌几乎没有活性。急性支气管炎、扁桃体炎和社区获得性肺炎的常见致病菌是溶血性链球菌、肺炎链球菌(G+菌)、厌氧菌,β-内酰胺类抗生素是首选药物,通常不使用氨基糖苷类抗生素。

二、雾化吸入导致的严重不良反应

国内庆大霉素注射液雾化吸入的适应证非常广泛,不良反应的报道也较多。

1、雾化吸入可引起过敏性休克

氨基糖苷类可引起过敏反应,特别是局部用药时。某些过敏反应可归因于庆大霉素注射液中的附加剂亚硫酸氢钠。

2、雾化吸入可引起听力减退

高音耳鸣是听力减退的先兆,如果继续用药,几天后可发展为听力损害。常人之间谈话属于低音频,此时患者并未感觉到听力困难,因此很容易被忽视。氨基糖苷类引起的耳毒性几乎不可逆,而且存在遗传相关性,某些家族中部分人仅接触单剂量就会出现耳聋。

3、雾化吸入可引起婴儿蛋白尿

使用氨基糖苷类药物几日后有8~26%的患者可出现轻度肾损害,大多数是可逆的。氨基糖苷类在近曲肾小管细胞中的积蓄和滞留是造成肾毒性的原因。由于近曲肾小管细胞有重建的能力,肾功能损害几乎都是可逆的。

4、雾化吸入可诱发老年人黑毛舌

黑毛舌病因与口腔菌群失调及全身抵抗力下降有关。庆大霉素雾化吸入引起口腔菌丛失去平衡,舌背丝状乳头过度增生,霉菌和产色微生物过度繁殖,因而出现色素沉着。

特别提醒:庆大霉素注射液雾化吸入,可诱导耐药菌的产生;雾化吸入属于超说明书用药,极易导致医患纠纷。

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  2. [GetPortalCommentsPageByObjectIdResponse(id=1840560, encodeId=ed07184056086, content=<a href='/topic/show?id=9401204912f' target=_blank style='color:#2F92EE;'>#不良反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20491, encryptionId=9401204912f, topicName=不良反应)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Sun Jul 15 00:00:00 CST 2018, time=2018-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322806, encodeId=cc5e322806c3, content=很好的文献.对临床工作很有帮助, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/PiajxSqBRaELCAs1uRBgDoWqJaBltta2Y7fTibyM6wYf94osSMg5CCm9oy7JrdcXPqh1DrCdn5IxO4BE8ZLEiaQXQ/0, createdBy=978a1675334, createdName=xiaogan8479, createdTime=Sat Jun 09 13:08:05 CST 2018, time=2018-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1404878, encodeId=008e14048e81e, content=<a href='/topic/show?id=7f234920369' target=_blank style='color:#2F92EE;'>#庆大霉素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49203, encryptionId=7f234920369, topicName=庆大霉素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74f82496953, createdName=shizhenshan, createdTime=Mon Jun 04 13:00:00 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1457734, encodeId=ad68145e734fa, content=<a href='/topic/show?id=e2d1988611e' target=_blank style='color:#2F92EE;'>#雾化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98861, encryptionId=e2d1988611e, topicName=雾化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Mon Jun 04 13:00:00 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321078, encodeId=08fb3210e811, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 03 08:17:29 CST 2018, time=2018-06-03, status=1, ipAttribution=)]
    2018-06-09 xiaogan8479

    很好的文献.对临床工作很有帮助

    0

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  4. [GetPortalCommentsPageByObjectIdResponse(id=1840560, encodeId=ed07184056086, content=<a href='/topic/show?id=9401204912f' target=_blank style='color:#2F92EE;'>#不良反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20491, encryptionId=9401204912f, topicName=不良反应)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Sun Jul 15 00:00:00 CST 2018, time=2018-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322806, encodeId=cc5e322806c3, content=很好的文献.对临床工作很有帮助, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/PiajxSqBRaELCAs1uRBgDoWqJaBltta2Y7fTibyM6wYf94osSMg5CCm9oy7JrdcXPqh1DrCdn5IxO4BE8ZLEiaQXQ/0, createdBy=978a1675334, createdName=xiaogan8479, createdTime=Sat Jun 09 13:08:05 CST 2018, time=2018-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1404878, encodeId=008e14048e81e, content=<a href='/topic/show?id=7f234920369' target=_blank style='color:#2F92EE;'>#庆大霉素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49203, encryptionId=7f234920369, topicName=庆大霉素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74f82496953, createdName=shizhenshan, createdTime=Mon Jun 04 13:00:00 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1457734, encodeId=ad68145e734fa, content=<a href='/topic/show?id=e2d1988611e' target=_blank style='color:#2F92EE;'>#雾化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98861, encryptionId=e2d1988611e, topicName=雾化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Mon Jun 04 13:00:00 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321078, encodeId=08fb3210e811, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 03 08:17:29 CST 2018, time=2018-06-03, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1840560, encodeId=ed07184056086, content=<a href='/topic/show?id=9401204912f' target=_blank style='color:#2F92EE;'>#不良反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20491, encryptionId=9401204912f, topicName=不良反应)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Sun Jul 15 00:00:00 CST 2018, time=2018-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322806, encodeId=cc5e322806c3, content=很好的文献.对临床工作很有帮助, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/PiajxSqBRaELCAs1uRBgDoWqJaBltta2Y7fTibyM6wYf94osSMg5CCm9oy7JrdcXPqh1DrCdn5IxO4BE8ZLEiaQXQ/0, createdBy=978a1675334, createdName=xiaogan8479, createdTime=Sat Jun 09 13:08:05 CST 2018, time=2018-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1404878, encodeId=008e14048e81e, content=<a href='/topic/show?id=7f234920369' target=_blank style='color:#2F92EE;'>#庆大霉素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49203, encryptionId=7f234920369, topicName=庆大霉素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74f82496953, createdName=shizhenshan, createdTime=Mon Jun 04 13:00:00 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1457734, encodeId=ad68145e734fa, content=<a href='/topic/show?id=e2d1988611e' target=_blank style='color:#2F92EE;'>#雾化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98861, encryptionId=e2d1988611e, topicName=雾化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Mon Jun 04 13:00:00 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321078, encodeId=08fb3210e811, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun Jun 03 08:17:29 CST 2018, time=2018-06-03, status=1, ipAttribution=)]
    2018-06-03 张新亮1853311252142e2fm

    好文献学习了

    0

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耳鼓室内庆大霉素疗法已经被广泛地应用到美尼尔氏综合征的衰弱症状的临床治疗。但是,这种疗法的潜在副作用是产生耳蜗毒性,并且听力损失程度与庆大霉素在耳蜗中的浓度大小成正比。最近研究人员发现,庆大霉素能够容易地通过豚鼠卵圆窗结构被吸收。另外,研究人员利用前庭和耳蜗功能量化测量方法检测了小量庆大霉素处理的豚鼠镫骨底板后对前庭的作用效应。分别在一周和两周处理后,通过记录头部线性加速反应的短潜伏前庭诱发电位,

Lancet:鼓室内注射甲基强的松龙治疗梅尼埃尔氏病,疗效如何?

梅尼埃尔氏病以严重的眩晕发作和听力损失为特点。对于难治性梅尼埃尔氏病的标准治疗方法鼓室内注射庆大霉素,可以改善眩晕,但是会损害前庭功能,以及导致听力恶化。 研究目的是,比较鼓室内注射糖皮质激素甲基强的松龙与庆大霉素,对梅尼埃尔氏病的疗效。 研究纳入18-70岁难治性梅尼埃尔氏病患者,共计60名,按1:1随机分为鼓室内注射糖皮质激素甲基强的松龙(62·5 mg/mL,n=30)或庆大霉素

PLos One:庆大霉素在感染性心内膜炎治疗中的药代动力学模型

庆大霉素在个体之间的半衰期和分布体积(Vd)都有很大变化。因此,需要监测和准确预测其血清水平以优化药物的有效性并尽量减少其毒性。目前,有两种药代动力学模型用于预测成年人的庆大霉素剂量。但是,对于心内膜炎患者,最佳模型尚未可知。近期,一项发表在杂志PLos One上的研究旨在:1)为心内膜炎患者评估最佳模型;和2)评估心内膜炎和现有的模型是否可以准确预测出血清水平。此项研究进行了回顾性观察性两队列研

Microb Drug Resist:精油的协同抗菌作用或可用于多重耐药菌的治疗

本研究旨在探究几种选定的市售精油和庆大霉素在对抗产超广谱β-内酰胺酶(ESBL)和产新德里金属-β-内酰胺酶-1(NDM-1)肺炎克雷伯菌分离株之间可能产生的协同效应。 通过双盘协同试验证实了产ESBLs。在所测试的菌株中发现了blaNDM-1基因阳性的菌株。使用肺炎克雷伯菌ATCC BAA-1705 TM菌株作为对照。使用方格棋法评估9种精油的协同作用和添加剂作用:香菜,茴香,薄荷,天竺葵