基于FAERS数据库对环丙沙星致过敏的风险分析
Risk Analysis of Ciprofloxacin-Associated Allergy Based on the FAERS Database
DOI: 10.12677/acm.2024.1461800, PDF, HTML, XML, 下载: 24  浏览: 42  科研立项经费支持
作者: 聂 晶, 杨 果, 乔丹丹, 张 渊*, 黎 丹*:浙江省人民医院毕节医院药学部,贵州 毕节
关键词: 环丙沙星FAERS过敏急性肾损伤Ciprofloxacin FAERS Allergy Acute Kidney Injury
摘要: 目的:基于FAERS数据库对环丙沙星(CFX)致过敏事件的信号挖掘研究,主要为探讨CFX诱导过敏反应的风险,为临床合理用药提供参考。方法:研究使用的信号生成方法为频数法,提取数据库中2018~2023年共24个季度的不良反应报告数据,运用报告比值比法(ROR)和综合标准法(MHRA)进行信号挖掘。得到有效信号后,再利用MedDRA术语集进行汉化及系统归类。结果:共检出81,725次以CFX为首的不良事件(ADE)报告,检测得到56,002个有效ADE信号,共累及23个不同系统器官(SOC),主要集中在各种肌肉骨骼及结缔组织疾病、各类神经系统疾病、全身性疾病及给药部位各种反应等。对CFX致过敏不良事件按照MedDRA SMQ狭义水平(standardized MedDRA query, SMQ)进行分类汇总,获得过敏性/类过敏性休克病症(SMQ)、速发严重过敏反应(SMQ)相关的ADE报告总计1830例报告,共34个有效信号,其中急性肾损伤的上报例数最多(n = 382),其次是荨麻疹(n = 325)。结论:对于药物过敏事件的发生人们往往关注的是常规的过敏体征,如皮疹,呼吸困难等,忽略了CFX引起急性肾损伤这一ADE的发生。因此,临床在使用CFX的过程中,除了监测患者是否有皮疹,水肿等情况发生,还应加强患者出入量的监测;合并过敏体质、肾脏系统等基础疾病的患者需加强评估,以确保临床合理用药。
Abstract: Objective: A signal mining study of ciprofloxacin (CFX)-induced anaphylactic events based on the FAERS database was conducted mainly to explore the risk of CFX-induced anaphylactic reactions and to provide a reference for the rational use of drugs in the clinic. Methods: The signal generation method used in the study was the frequency counting method, which extracted the adverse reaction report data from the database for a total of 24 quarters from 2018 to 2023, and applied the reporting ratio-ratio (ROR) and medicines and healthcare products regulatory agency (MHRA) methods for signal mining. After obtaining valid signals, the MedDRA terminology set was then used for handwriting and systematic categorisation. Results: A total of 81,725 CFX-led adverse events (ADE) were detected, and 56,002 valid ADE signals were obtained, involving 23 different system organs (SOCs), mainly focusing on a variety of musculoskeletal and connective tissue disorders, various neurological disorders, systemic disorders, and a variety of reactions at the site of drug administration. The CFX allergic adverse events were categorised and summarised according to standardised MedDRA query (SMQ), and a total of 1830 reports of anaphylactic/anaphylaxis-like conditions (SMQ), rapid-onset severe allergic reactions (SMQ)-associated ADE were obtained with a total of 34 valid signals, of which the highest number of reports (n = 1) was for acute kidney injury (AKI). highest number of reported cases (n = 382), followed by urticaria (n = 325). Conclusion: For the occurrence of drug allergic events people tend to focus on routine allergic signs, such as rash, dyspnoea, etc., ignoring the occurrence of acute kidney injury caused by CFX as an ADE. Therefore, in the process of using CFX in the clinic, in addition to monitoring whether the patients have skin rash, oedema, etc., should also strengthen the monitoring of the patient’s intake and output; combined with the allergic body, the renal system and other underlying diseases of the patients need to be strengthened to assess, in order to ensure the rational use of clinical medication.
文章引用:聂晶, 杨果, 乔丹丹, 张渊, 黎丹. 基于FAERS数据库对环丙沙星致过敏的风险分析[J]. 临床医学进展, 2024, 14(6): 490-495. https://doi.org/10.12677/acm.2024.1461800

1. 前言

细菌感染是全球健康的重大威胁,是大多数医院获得性感染的原因,导致了广泛的死亡率和全球医疗系统的负担[1]。第二代氟喹诺酮–环丙沙星(CFX)具有良好的抗菌活性和药代动力学特性,副作用少,已被引入临床实践,用于治疗各种细菌感染约30年,抗菌谱广,抗菌活性及组织穿透性较强,可用于衣原体、支原体、革兰阴性菌、革兰阳性菌、铜绿假单胞菌等感染[2] [3]。CFX主要药物不良反应主要表现为皮疹、瘙痒、恶心、呕吐等[4]。虽然国内外对CFX安全性相关报道众多[5] [6],对CFX致过敏的分析局限于个案报道和临床观察研究,缺少信号挖掘研究。因此,关注CFX的潜在的ADE信号,挖掘其可能存在的过敏相关ADE是非常重要且有意义的。

2. 资料与方法

数据来源

本研究数据来源于美国FAERS数据库,这是一个自愿的自发报告数据库,提供了全球医疗保健专业人员,消费者和制造商提交给美国FDA的不良事件和用药错误报告的信息,并按照季度进行发布,该数据以可扩展标记语言(Extensible Markup Language, XML)和逗号分隔值文件(Comma-Separated Values, CSV)形式储存[7]。将首要怀疑药物引起的ADE,根据个人信息记录(DEMO)表进行去重处理后,导入MySQL5.7进行分析,计算方法等详见图1

Figure 1. Flow chart of data extraction of CFX (ADE: adverse drug event; ROR: reporting odds ratios; MHRA: medicines and healthcare products regulatory agency)

1. CFX数据提取流程图(ADE:不良事件;ROR:报告比值法;MHRA:综合标准法)

3. 结果

3.1. 有效ADE分析

研究目标时段共计ADE报告8,010,432例次,其中CFX为首要怀疑药物的唯一报告有81,725例,去重后得到有效信号共56,002个,共累及23个SOC。

3.2. CFX致过敏分析

对CFX致过敏不良事件按照MedDRA SMQ狭义水平(standardized MedDRA query, SMQ)进行分类汇总,获得过敏性/类过敏性休克病症(SMQ)、速发严重过敏反应(SMQ)相关的ADE报告总计1830例报告,共34个有效信号。敏性/类过敏性休克病症(SMQ)主要包含急性肾损伤,无尿,共计上报例次403;速发严重过敏反应(SMQ)包括过敏性水肿、喉头水肿、速发严重过敏反应、呛噎感、发绀等32个PT,共计上报例次为1427。其中,急性肾损伤的上报例数最多(n = 382),其次是荨麻疹(n = 325),固定皮疹的信号强度最强(PRR = 15.28,卡方χ2 = 349.49)。详见表1

Table 1. Classification of allergy ADEs caused by CFX

1. CFX致过敏不良事件分类

分类

环丙沙星

PT

报告数量

χ2

过敏性/类过敏性休克病症(SMQ)

急性肾损伤

382

226.29

无尿

21

36.79

过敏性水肿

3

9.41

速发严重过敏反应(SMQ)

速发严重过敏反应

91

69.75

过敏性休克

40

29.00

呛噎感

8

4.22

循环性虚脱

56

175.59

发绀

26

29.44

眼睑水肿

31

86.30

面部水肿

35

54.11

固定皮疹

27

349.49

红斑

14

39.44

过敏性冠状动脉痉挛综合征

14

87.60

喉水肿

8

4.12

唇部水肿

18

58.38

唇部肿胀

55

41.99

肿胀

7

42.56

口肿胀

18

26.49

口水肿

3

10.78

眼眶周围水肿

21

94.57

咽部水肿

31

61.42

咽部肿胀

46

141.40

瘙痒

38

41.54

皮疹

42

47.60

呼吸窘迫

40

21.28

休克综合征

3

18.80

喘鸣

7

13.24

肿胀

187

159.66

面肿

99

59.65

肿舌

56

60.89

咽喉缩紧感

52

59.75

舌水肿

18

77.63

I型超敏反应

8

8.56

荨麻疹

325

331.50

4. 讨论

笔者通过提取FAERS数据库中2018~2023年24个季度CFX ADE信号,共得到首要怀疑药物为81,725例,产生的ADE信号与CFX药品说明书重合性较好,证明了本研究方法的可靠性。

近年来,有关CFX致过敏的报道逐渐增多[8]。在一项环丙沙星致不良反应213例文献分析得到CFX的ADE临床表现以过敏性休克(65例,30.52%)为主,严重者可致死亡(3例,1.41%),并提示首次静脉滴注的前10 min和过敏性休克发生后的30 min是预防、发现、治疗环丙沙星致过敏性休克的关键时段。此外,CFX的不良反应信号分析中,我们发现其致急性肾损伤的上报例次最多。Kr等[9]在一项个案报道中提到一例在使用CFX后出现急性肾损伤,并认为出现急性肾损伤的病因可能是多因素的,包括经口摄入量减少导致的脱水、腹泻和环丙沙星诱导的肾毒性。急性肾损伤的发生可能有多种机制,包括间质性肾炎、横纹肌溶解或肾小管内结晶导致肾内梗阻等[10] [11]

目前关于CFX致急性肾损伤的报告较少,关于其作用机制亟待研究。鉴于此,医生在使用CFX的过程中可能会忽略这一不良反应的发生,而且会将此归于CFX对肾脏系统的损害而非由于过敏引起,导致呼吸窘迫等严重不良事件的发生。因此,在使用CFX时应当加强患者尿量、肾功能以及常见过敏反应的监测,以确保CFX的安全及合理用药。

5. 结论

本研究采用ROR法和MHRA法对FAERS数据库中CFX的ADE信号进行挖掘分析,其结果与西普乐(乳酸环丙沙星氯化钠注射液,厂家:Bayer Vital GmbH)的药品说明书重合性较好。数据显示,CFX与过敏反应的发生相关性较高,尤其是急性肾损伤、荨麻疹等ADE的报告数较多,在使用CFX的过程中,如果患者是过敏体质,应加强评估。以上结果供临床参考。

基金项目

本研究主要由毕科合重大专项[2023] 2-1项目支持。

NOTES

*通讯作者。

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