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中华肾病研究电子杂志 ›› 2023, Vol. 12 ›› Issue (01) : 1 -7. doi: 10.3877/cma.j.issn.2095-3216.2023.01.001

论著

慢性肾衰竭患者发生抗生素脑病的预测模型的建立和评价
余建峰1, 金劲松2,(), 龙利1, 徐敏1, 金晟1, 张继波1, 刘浩1   
  1. 1. 430030 武汉,江汉大学附属湖北省第三人民医院肾病科
    2. 430070 武汉,湖北省中医院肾病科
  • 收稿日期:2022-05-31 出版日期:2023-02-28
  • 通信作者: 金劲松
  • 基金资助:
    2021年湖北省卫生健康委员会科研项目(ZY2021M071)

Establishment and evaluation of prediction model for antibiotic-associated encephalopathy in patients with chronic renal failure

Jianfeng Yu1, Jinsong Jin2,(), Li Long1, Min Xu1, Sheng Jin1, Jibo Zhang1, Hao Liu1   

  1. 1. Department of Nephrology, Hubei No.3 People′s Hospital Affiliated to Jianghan University, Wuhan 430030
    2. Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430070; Hubei Province, China
  • Received:2022-05-31 Published:2023-02-28
  • Corresponding author: Jinsong Jin
引用本文:

余建峰, 金劲松, 龙利, 徐敏, 金晟, 张继波, 刘浩. 慢性肾衰竭患者发生抗生素脑病的预测模型的建立和评价[J/OL]. 中华肾病研究电子杂志, 2023, 12(01): 1-7.

Jianfeng Yu, Jinsong Jin, Li Long, Min Xu, Sheng Jin, Jibo Zhang, Hao Liu. Establishment and evaluation of prediction model for antibiotic-associated encephalopathy in patients with chronic renal failure[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(01): 1-7.

目的

探讨慢性肾衰竭(CRF)患者发生抗生素相关性脑病(AAE)的危险因素,并建立预测模型。

方法

回顾性分析784例CRF患者的临床资料,所有患者均使用了抗生素治疗,根据患者有无发生AAE,分为AAE组(103例)和非AAE组(681例),将两组患者有统计学意义的临床指标纳入Logistic回归分析,得出AAE发生的独立危险因素并建立预测模型,并使用列线图展示模型。采用ROC曲线、校准曲线判定该模型的区分度及校准度,使用Bootstrap法对模型进行内部验证。

结果

多变量Logistic回归分析显示,年龄大(OR 1.033, 95%CI: 1.012~1.054)、低血浆白蛋白(OR 0.852, 95%CI:0.802~0.905)、低GFR(OR 0.963, 95%CI:0.940~0.988)、单用β-内酰胺酶抑制剂复方制剂类抗生素(OR 3.827, 95%CI:1.528~9.584)、两种或两种以上抗生素联用(OR 2.913, 95%CI:1.187~7.149)以及抗生素未减量使用(OR 0.343, 95%CI: 0.212~0.553)均为CRF患者发生AAE的独立影响因素。列线图模型的ROC曲线下面积为0.808(95%CI:0.770~0.846),内部验证C-统计量0.808。

结论

本研究建立的预测模型可对临床上早期识别CRF患者的AAE风险及实施预防性措施提供一定参考价值。

Objective

To explore the risk factors of the occurrence of antibiotic-associated encephalopathy (AAE) in patients with chronic renal failure (CRF) and establish a prediction model.

Methods

The clinical data of 784 patients with CRF were retrospectively analyzed. All the patients had received treatment of antibiotics. According to whether the patients had AAE or not, they were divided into AAE group (n=103) and non-AAE group (n=681). The clinical indicators with statistical differences between the two groups were included in logistic regression analysis to obtain the independent risk factors of AAE and establish a prediction model which was shown by the nomogram. Receiver operating characteristic (ROC) curve and calibration curve were used to assess the discrimination and calibration of the model, and Bootstrap method was used for internal validation.

Results

The multivariate logistic regression analysis showed that aging(OR 1.033, 95%CI: 1.012-1.054), low plasma albumin(OR 0.852, 95%CI: 0.802-0.905), low GFR(OR 0.963, 95%CI: 0.940-0.988), separate use of β-lactamase inhibitor compound preparation antibiotic (OR 3.827, 95%CI: 1.528-9.584), combination of two or more antibiotics(OR 2.913, 95%CI: 1.187-7.149), and use of antibiotics without dose reduction (OR 343, 95%CI: 0.212-0.553) were all independent influencing factors for the occurrence of AAE in CRF patients. The area under the ROC curve (AUC) of the nomogram model was 0.808(95%CI: 0.770-0.846)with an internal verification C-index of 0.808.

Conclusion

The prediction model established in this study may provide some reference value for the early identification of AAE risk and the implementation of preventive measures in CRF.

表1 两组患者一般资料及实验室检测指标比较
临床变量 非抗生素脑病组(n=681) 抗生素脑病组(n=103) t/χ2 P
年龄(岁) 53.06±13.25 60.63±12.48 -5.445 <0.001
男[例(%)] 392(57.6) 58(56.3) 0.057 0.811
BMI(kg/m2) 23.36±2.56 23.19±3.01 0.612 0.540
维持性透析[例(%)] 251(36.9) 37(35.9) 0.034 0.854
感染类型[例(%)]     2.788 0.425
肺部感染 289(42.4) 47(45.6)    
泌尿系感染 232(34.1) 27(26.2)    
皮肤及皮下组织感染 120(17.6) 21(20.4)    
其他 40(5.9) 8(7.8)    
合并高血压[例(%)] 312(45.8) 40(46.2) 1.762 0.184
合并2型糖尿病[例(%)] 301(44.2) 54(52.4) 2.444 0.118
合并脑血管疾病[例(%)] 229(33.6) 47(45.6) 5.652 0.017
血红蛋白(g/L) 97.08±13.19 95.94±10.48 0.836 0.403
血浆白蛋白(g/L) 33.83±5.35 29.80±3.34 10.395 <0.001
GFR[ml/(min·1.73 m2)] 25.07±14.42 17.73±6.72 8.504 <0.001
血钾(mmol/L) 4.46±0.90 4.54±1.17 -0.637 0.525
血钙(mmol/L) 2.04±0.34 2.07±0.30 -1.009 0.313
PCT(ng/ml) 2.66±1.33 2.86±1.13 -1.639 0.103
CO2-CP(mmol/L) 20.35±3.89 20.99±2.96 -1.954 0.052
抗生素使用时间≥7 d[例(%)] 408(59.9) 69(67.0) 1.882 0.170
抗生素使用类别[例(%)]     14.760 0.011
单用头孢菌素类 118(17.3) 17(16.5)    
单用青霉素类 86(12.6) 4(3.9)    
单用喹诺酮类 84(12.3) 13(12.6)    
单用β-内酰胺酶抑制剂复方制剂类 120(17.6) 29(28.2)    
两种或以上抗生素联用 185(27.2) 33(32.0)    
其他 88(12.9) 7(6.8)    
抗生素减量使用[例(%)] 381(55.9) 32(31.1) 22.215 <0.001
表2 自变量赋值
表3 Logistic回归分析结果
图1 慢性肾衰竭患者发生抗生素相关性脑病预测模型的列线图注:Points:得分;Total Points:总得分
图2 慢性肾衰竭患者发生抗生素相关性脑病预测模型的受试者工作特征曲线
图3 慢性肾衰竭患者发生抗生素相关性脑病预测模型的校准曲线注:AAE:抗生素相关性脑病;Apparent:参考线;Bias-corrected:校正曲线;Ideal:理想曲线
[1]
Primavera A, Cocito L, Audenino D. Nonconvulsive status epilepticus during cephalosporin therapy [J]. Neuropsychobiology, 2004, 49(4): 218-222.
[2]
Chang YM. Cefepime-induced nonconvulsive status epilepticus as a cause of confusion in an elderly patient [J]. J Formos Med Assoc, 2015, 114(3): 290-291.
[3]
Martin TCS, Chow S, Johns ST, et al. Ceftaroline-associated encephalopathy in patients with severe renal impair ment [J]. Clin Infect Dis, 2020, 70(9): 2002-2004.
[4]
Fugate JE, Kalimullah EA, Hocker SE, et al. Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy [J]. Crit Care, 2013, 17(6): R264.
[5]
Sonck J, Laureys G, Verbeelen D. The neurotoxicity and safety of treatment with cefepime in patients with renal failure [J]. Nephrol Dial Transplant, 2008, 23(3): 966-970.
[6]
张佩殷,黄新忠,范亚平,等. 慢性肾脏病并发抗生素脑病的危险因素及防治[J]. 中国现代医学杂志2014, 24(15): 90-93.
[7]
龚昌华,叶树位. 终末期肾脏病患者应用头孢他啶后并发抗生素脑病的相关性分析[J]. 中国药房2015, 26(36): 5083-5084.
[8]
郭爱莉. 头孢菌素致慢性肾衰竭患者抗生素脑病25例回顾性分析[J]. 药物流行病学杂志2015(4): 228-230.
[9]
Nakagawa R, Sato K, Uesaka Y, et al. Cefepime-induced encephalopathy in end-stage renal disease patients [J]. J Neurol Sci, 2017, 376: 123-128.
[10]
Chow KM, Hui AC, Szeto CC. Neurotoxicity induced by beta-lactam antibiotics: from bench to bedside [J]. Eur J Clin Microbiol Infect Dis, 2005, 24(10): 649-653.
[11]
Garces EO, Andrade de Anzambuja MF, da Silva D, et al. Renal failure is a risk factor for cefepime-induced encephalopathy [J]. J Nephrol, 2008, 21(4): 526-534.
[12]
Zhang J, Huang C, Li H, et al. Antibiotic-induced neurotoxicity in dialysis patients: a retrospective study [J]. Ren Fail, 2013, 35(6): 901-905.
[13]
Kim KB, Kim SM, Park W, et al. Ceftiaxone-induced neurotoxicity: case report, pharmacokinetic considerations, and literature review [J]. J Korean Med Sci, 2012, 27(9): 1120-1123.
[14]
Sato Y, Morita H, Wakasugi H, et al. Reversible choreoathetosis after the administration of ceftriaxone sodium in patients with end-stage renal disease [J]. Am J Med Sci, 2010, 340(5): 382-384.
[15]
Tan ML, Tun WWW. Reversible choreoathetosis in a patient with end-stage renal disease from administration of ceftriaxone [J]. Cureus, 2019, 11(9): e5764.
[16]
Suzuki S, Naito S, Numasawa Y, et al. Encephalopathy induced by high plasma and cerebrospinal fluid ceftriaxone concentrations in a hemodialysis patient [J]. Intern Med, 2019, 58(12): 1775-1779.
[17]
Jallon P, Fankhauser L, Du Pasquier R, et al. Severe but reversible encephalopathy associated with cefepime [J]. Neurophysiol Clin, 2000, 30(6): 383-386.
[18]
Guo Y, Shao X, Zhang L, et al. A case of suspected antibiotic-associated encephalopathy in a patient undergoing long-term peritoneal dialysis [J]. J Int Med Res, 2020, 48(5): 300060520924507.
[19]
Lattanzio F, Landi F, Bustacchini S, et al. Geriatric conditions and the risk of adverse drug reactions in older adults: a review [J]. Drug Saf, 2012, 35(Suppl 1): 55-61.
[20]
黄玉斌,李赞东. 国内外头孢吡肟不良反应综述[J]. 中国执业药师201613(5): 32-35.
[21]
Mattappalil A, Mergenhagen KA. Neurotoxicity with antimicrobials in the elderly: a review [J]. Clin Ther, 2014, 36(11): 1489-1511.
[22]
贺瑞萍,郭永英. 抗生素类药物对神经系统的毒性反应[J]. 中国药事2004, 18(12): 774-775.
[23]
Alkharfy KM, Kellum JA, Frye RF, et al. Effect of ceftazidime on systemic cytokine concentrations in rats [J]. Antimicrob Agents Chemother, 2000, 44(11): 3217-3219.
[24]
Sunagawa M, Matsumura H, Sumita Y, et al. Structural features resulting in convulsive activity of carbapenem compounds: effect of C-2 side chain [J]. J Antibiot (Tokyo), 1995, 48(5): 408-416.
[25]
De Sarro A, Imperatore C, Mastroeni P, et al. Comparative convulsant potencies of two carbapenem derivatives in C57 and DBA/2 mice [J]. J Pharm Pharmacol, 1995, 47(4): 292-296.
[26]
Weihrauch TR, Köhler H, Höffler D. Cerebral toxicity of penicillins in relation to their hydrophobic character [J]. Naunyn Schmiedebergs Arch Pharmacol, 1975, 289(1): 55-64.
[27]
唐学文,贾运涛,田晓江,等. 左氧氟沙星、莫西沙星和环丙沙星上市后安全警戒信号的挖掘与评价——基于真实世界不良反应研究[J]. 中国新药杂志2018, 27(5): 596-602.
[28]
Calandra G, Lydick E, Carrigan J, et al. Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin [J]. Am J Med, 1988, 84(5): 911-918.
[29]
Chow KM, Szeto CC, Hui AC, et al. Mechanisms of antibiotic neurotoxicity in renal failure [J]. Int J Antimicrob Agents, 2004, 23(3): 213-217.
[30]
Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections [J]. Clin Microbiol Rev, 2010, 23(4): 858-883.
[31]
Grill MF, Maganti R. Cephalosporin-induced neurotoxicity: clinical manifestations, potential pathogenic mechanisms, and the role of electroencephalographic monitoring [J]. Ann Pharmacother, 2008, 42(12): 1843-1850.
[32]
Huang WT, Hsu YJ, Chu PL, et al. Neurotoxicity associated with standard doses of piperacillin in an elderly patient with renal failure [J]. Infection, 2009, 37(4): 374-376.
[33]
Schliamser SE, Cars O, Norrby SR. Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis [J]. J Antimicrob Chemother, 1991, 27(4): 405-425.
[34]
Brouns R, De Deyn PP. Neurological complications in renal failure: a review [J]. Clin Neurol Neurosurg, 2004, 107(1): 1-16.
[35]
马雁,沈皓. 头孢吡肟致尿毒症维持性血液透析患者抗生素脑病的临床分析[J]. 临床内科杂志2012, 29(9): 612-613.
[36]
彭梅,汪贤聪,罗凯,等. 尿毒症患者抗生素脑病23例临床分析[J]. 实用医院临床杂志2012, 9(5): 202-203.
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