Service of Infectious Diseases, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
Spanish Network for Research in Infectious Diseases (REIPI), Madrid, Spain.
Clin Microbiol Rev. 2019 Aug 28;32(4). doi: 10.1128/CMR.00031-19. Print 2019 Sep 18.
In recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR) has become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options. and treatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDR infections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other "old" antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDR strains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDR , especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.
近年来，所谓的耐多药或广泛耐药（MDR/XDR）高风险克隆在全球范围内的传播已成为公共卫生威胁。本文综述了其耐药机制、流行病学和临床影响以及目前和即将出现的治疗选择。还讨论了治疗研究和药代动力学和药效学（PK/PD）模型。多粘菌素被视为一种重要的治疗选择，概述了剂量、药代动力学和药效学以及它们对 MDR/XDR 感染的临床疗效。还讨论了它们的治疗窗口狭窄和联合治疗的潜力。本文还回顾了其他“老”抗菌药物，如某些β-内酰胺类、氨基糖苷类和磷霉素。新的抗假单胞菌药物以及正在研发中的药物也进行了综述。头孢洛扎他唑巴坦对很大一部分 MDR/XDR 菌株具有临床活性，描述了其微生物学和临床数据，以及关于如何改进其对这些细菌的使用的建议，以及头孢他啶-阿维巴坦的建议，它对 MDR/XDR 具有更好的活性，尤其是具有某些特定耐药机制的菌株。专门有一节用于回顾新的活性药物，如亚胺培南-雷巴他定、头孢吡肟-齐多夫坦、头孢地尔夫、美罗培南-法硼巴坦。最后，还描述了其他治疗策略，如疫苗、抗体、细菌素、抗群体感应和噬菌体的使用，作为未来的选择。
