碳青霉烯类耐药革兰阴性菌感染的药物治疗进展

Progress in pharmacological treatment of carbapenem-resistant gram-negative bacteria infections

  • 摘要: 针对碳青霉烯类耐药革兰阴性菌(CR-GNB)的严峻挑战,本文基于近年来高等级循证证据与药代动力学/药效学(PK/PD)研究,从临床药学视角系统综述新型抗菌药物的个体化应用策略。新型酶抑制剂复方制剂(如头孢他啶-阿维巴坦、氨曲南-阿维巴坦、头孢洛生-他唑巴坦、亚胺培南西司他丁-瑞来巴坦、舒巴坦-度洛巴坦)与头孢德罗等,分别精准填补了产肺炎克雷伯菌碳青霉烯酶(KPC)或金属酶的碳青霉烯类耐药肠杆菌目细菌(CRE)、鲍曼不动杆菌(CRAB)及难治性耐药性铜绿假单胞菌(DTR-PA)的治疗空白; 多黏菌素、四环素类等传统药物亦在优化后保留特定地位。最大化临床价值需践行"精准诊断-靶向选药-剂量优化"一体化策略。依托酶型匹配与治疗药物监测(TDM),实施基于PK/PD的个体化给药,是改善患者预后并遏制耐药发展的关键。

     

    Abstract: Addressing the severe challenge posed by carbapenem-resistant gram-negative bacteria (CR-GNB), this review systematically evaluates individualized application strategies for novel antimicrobial agents from a clinical pharmacy perspective based on the high-level evidence and pharmacokinetic/pharmacodynamic (PK/PD) studies in recent years.Novel enzyme inhibitor preparations(such as ceftazidime-avibactam,aztreonam-avibactam,ceftolozane-tazobactam,imipenem/cilastatin-relebactam,and sulbactam-durlobactam)and cefiderocol have precisely filled the gaps of treatment of carbapenem-resistant Enterobacterales (CRE) producing Klebsiella pneumoniae carbapenemase (KPC) or metallo-"β" -lactamases, carbapenem-resistant Acinetobacter baumannii (CRAB),and difficult to treat resistance-Pseudomonas aeruginosa(DTR-AB).Furthermore,traditional drugs such as polymyxins and tetracyclines also retain certain clinical niches after the optimization of regimen. It is necessary to pursue the integrated strategy of"precise diagnosis,targeted drug selection, and dosage optimization" so as to maximize the clinical value. It is the key to implement the individualized drug administration based on PK/PD principles that is supported by enzyme profile matching and therapeutic drug monitoring (TDM) so as to improve the prognosis and curb the development of drug resistance.

     

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