抗微生物药物耐药时代中枢神经系统感染的创新突围

doi:10.3969/j.issn.1672-6731.2026.07.001

摘要/Abstract

摘要：

抗微生物药物耐药性的日益加剧使中枢神经系统抗感染治疗面临严峻挑战。血脑屏障和血-脑脊液屏障的存在限制了多数抗菌药物的脑脊液穿透性，而传统经验性治疗模式难以应对日趋复杂的耐药机制。本文拟从快速诊断、耐药机制指导的靶向治疗、新型抗菌药物临床证据及药代动力学/药效学导向的个体化治疗等方面系统综述中枢神经系统耐药菌感染领域的最新进展。

关键词: 医原性疾病, 中枢神经系统感染, 抗药性，微生物, 血脑屏障, 综述

Abstract:

The escalating burden of antimicrobial resistance poses formidable challenges to anti-infective therapy for central nervous system infections. The presence of the blood-brain barrier and blood-cerebrospinal fluid barrier restricts the cerebrospinal fluid penetration of most antimicrobial agents, while conventional empirical treatment regimens are increasingly inadequate to contend with evolving and complex resistance mechanisms. This article provides a systematic review of recent advances in the management of drug-resistant central nervous system infections, encompassing rapid diagnostic approaches, resistance mechanism-guided targeted therapy, emerging clinical evidence on novel antimicrobial agents, and pharmacokinetic/pharmacodynamic (PK/PD)-oriented individualized treatment strategies.

Key words: Iatrogenic disease, Central nervous system infections, Drug resistance, microbial, Blood-brain barrier, Review

中图分类号:

R741

李宁, 刘其会, 王璇, 张文宏. 抗微生物药物耐药时代中枢神经系统感染的创新突围[J]. 中国现代神经疾病杂志, 2026, 26(7): 679-685.

Ning LI, Qi-hui LIU, Xuan WANG, Wen-hong ZHANG. Innovative breakthroughs in the treatment of central nervous system infections in the era of antimicrobial resistance[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2026, 26(7): 679-685.

https://journal11.magtechjournal.com/cjcnn/CN/Y2026/V26/I7/679

图/表 1

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药物	摩尔质量	化学性质	蛋白结合率	脑脊液穿透率	常用剂量	细菌(例数)	治愈
头孢他啶-阿维巴坦^[4-11]	头孢他啶546.6 g/mol, 阿维巴坦287.23 g/mol	亲水性	头孢他啶 < 10%, 阿维巴坦6%~8%	头孢他啶3%~59%, 阿维巴坦10%~57%	2500 mg/次(包括头孢他啶2000 mg/次+阿维巴坦500 mg/次)静脉给药, 3次/d	CRKP(72例)、CRE(4例)、产ESBL的大肠埃希菌(1例)、CRPA(7例)、伯克霍尔德菌(1例)	总治愈率84.71%(72/85)
氨曲南联合头孢他啶-阿维巴坦^{[3-4, 12-14]}	氨曲南435.43 g/mol	中等亲脂性	氨曲南56%	氨曲南18%~27%	氨曲南2000 mg/次(3次/d)静脉给药, 建议与头孢他啶-阿维巴坦2500 mg/次(3次/d)同时给药	CRKP(2例)、嗜麦芽窄食单胞菌(1例)	均临床治愈
美罗培南-韦博巴坦^{[3-4, 15-16]}	美罗培南383.46 g/mol, 韦博巴坦297.14 g/mol	亲水性	美罗培南2%, 韦博巴坦33%	美罗培南5%~40%, 韦博巴坦4%~6%	数据有限	CRKP(9例)	6例临床治愈
头孢洛生-他唑巴坦^{[3-4, 17-19]}	头孢洛生666.69 g/mol	亲水性	头孢洛生16%~21%	头孢洛生7%~83%	3000 mg/次(包括头孢洛生2000 mg/次+他唑巴坦1000 mg/次)静脉给药, 3次/d	CRPA(6例)	5例临床治愈
舒巴坦-度洛巴坦^{[3-4, 20-23]}	舒巴坦233.24 g/mol, 度洛巴坦277.26 g/mol	亲水性	舒巴坦38%, 度洛巴坦10%	舒巴坦10%~37%, 度洛巴坦9%~26%	2000 mg/次(包括舒巴坦1000 mg/次+度洛巴坦1000 mg/次)静脉给药, 4次/d	CRAB(4例)	均临床治愈
亚胺培南-瑞来巴坦^[4]	亚胺培南299.35 g/mol, 瑞来巴坦366.39 g/mol	亲水性	亚胺培南20%, 瑞来巴坦22%	亚胺培南15%~27%, 瑞来巴坦(一)	不建议使用	—	—
头孢德罗^{[4, 21, 23-28]}	752.22 g/mol	中等亲脂性	40%~60%	3%~70%	2000 mg/次(4次/d)静脉给药	CRPA(8例)、CRAB10例)、CRKP(1例)	总治愈率15/19
头孢比罗^[29-31]	534.57 g/mol	亲水性	约16%	11.9%~36.5%	500 mg/次(3~4次/d)静脉给药	中间链球菌(1例)、金黄色葡萄球菌(3例)	均临床治愈
依拉环素^[32-34]	558.56 g/mol	亲水性	80%	< 5%	数据有限	CRAB(2例)	均临床治愈
特地唑胺^[35-37]	370.34 g/mol	中等亲脂性	70%~90%	5%	数据有限	诺卡菌(3例)、VRE(1例)	均临床治愈
康替唑胺^[38]	408.33 g/mol	中等亲脂性	90%	10%	数据有限	—	—

药物	摩尔质量	化学性质	蛋白结合率	脑脊液穿透率	常用剂量	细菌(例数)	治愈
头孢他啶-阿维巴坦^[4-11]	头孢他啶546.6 g/mol, 阿维巴坦287.23 g/mol	亲水性	头孢他啶 < 10%, 阿维巴坦6%~8%	头孢他啶3%~59%, 阿维巴坦10%~57%	2500 mg/次(包括头孢他啶2000 mg/次+阿维巴坦500 mg/次)静脉给药, 3次/d	CRKP(72例)、CRE(4例)、产ESBL的大肠埃希菌(1例)、CRPA(7例)、伯克霍尔德菌(1例)	总治愈率84.71%(72/85)
氨曲南联合头孢他啶-阿维巴坦^{[3-4, 12-14]}	氨曲南435.43 g/mol	中等亲脂性	氨曲南56%	氨曲南18%~27%	氨曲南2000 mg/次(3次/d)静脉给药, 建议与头孢他啶-阿维巴坦2500 mg/次(3次/d)同时给药	CRKP(2例)、嗜麦芽窄食单胞菌(1例)	均临床治愈
美罗培南-韦博巴坦^{[3-4, 15-16]}	美罗培南383.46 g/mol, 韦博巴坦297.14 g/mol	亲水性	美罗培南2%, 韦博巴坦33%	美罗培南5%~40%, 韦博巴坦4%~6%	数据有限	CRKP(9例)	6例临床治愈
头孢洛生-他唑巴坦^{[3-4, 17-19]}	头孢洛生666.69 g/mol	亲水性	头孢洛生16%~21%	头孢洛生7%~83%	3000 mg/次(包括头孢洛生2000 mg/次+他唑巴坦1000 mg/次)静脉给药, 3次/d	CRPA(6例)	5例临床治愈
舒巴坦-度洛巴坦^{[3-4, 20-23]}	舒巴坦233.24 g/mol, 度洛巴坦277.26 g/mol	亲水性	舒巴坦38%, 度洛巴坦10%	舒巴坦10%~37%, 度洛巴坦9%~26%	2000 mg/次(包括舒巴坦1000 mg/次+度洛巴坦1000 mg/次)静脉给药, 4次/d	CRAB(4例)	均临床治愈
亚胺培南-瑞来巴坦^[4]	亚胺培南299.35 g/mol, 瑞来巴坦366.39 g/mol	亲水性	亚胺培南20%, 瑞来巴坦22%	亚胺培南15%~27%, 瑞来巴坦(一)	不建议使用	—	—
头孢德罗^{[4, 21, 23-28]}	752.22 g/mol	中等亲脂性	40%~60%	3%~70%	2000 mg/次(4次/d)静脉给药	CRPA(8例)、CRAB10例)、CRKP(1例)	总治愈率15/19
头孢比罗^[29-31]	534.57 g/mol	亲水性	约16%	11.9%~36.5%	500 mg/次(3~4次/d)静脉给药	中间链球菌(1例)、金黄色葡萄球菌(3例)	均临床治愈
依拉环素^[32-34]	558.56 g/mol	亲水性	80%	< 5%	数据有限	CRAB(2例)	均临床治愈
特地唑胺^[35-37]	370.34 g/mol	中等亲脂性	70%~90%	5%	数据有限	诺卡菌(3例)、VRE(1例)	均临床治愈
康替唑胺^[38]	408.33 g/mol	中等亲脂性	90%	10%	数据有限	—	—

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Innovative breakthroughs in the treatment of central nervous system infections in the era of antimicrobial resistance

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