Giamarellou Helen, Karaiskos Ilias
1st Department of Internal Medicine-Infectious Diseases, Hygeia General Hospital, 4, Erythrou Stavrou & Kifisias, Marousi, 15123 Athens, Greece.
Antibiotics (Basel). 2022 Jul 26;11(8):1009. doi: 10.3390/antibiotics11081009.
Carbapenem resistance in Gram-negative bacteria has come into sight as a serious global threat. Carbapenem-resistant Gram-negative pathogens and their main representatives , , and are ranked in the highest priority category for new treatments. The worrisome phenomenon of the recent years is the presence of difficult-to-treat resistance (DTR) and pandrug-resistant (PDR) Gram-negative bacteria, characterized as non-susceptible to all conventional antimicrobial agents. DTR and PDR Gram-negative infections are linked with high mortality and associated with nosocomial infections, mainly in critically ill and ICU patients. Therapeutic options for infections caused by DTR and PDR Gram-negative organisms are extremely limited and are based on case reports and series. Herein, the current available knowledge regarding treatment of DTR and PDR infections is discussed. A focal point of the review focuses on salvage treatment, synergistic combinations (double and triple combinations), as well as increased exposure regimen adapted to the MIC of the pathogen. The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented.
革兰氏阴性菌对碳青霉烯类抗生素的耐药性已成为一个严重的全球威胁。耐碳青霉烯类革兰氏阴性病原体及其主要代表菌（如肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌）被列为新治疗方法的最高优先类别。近年来令人担忧的现象是出现了难以治疗的耐药性（DTR）和泛耐药（PDR）革兰氏阴性菌，其特征是对所有传统抗菌药物均不敏感。DTR和PDR革兰氏阴性菌感染与高死亡率相关，且主要与医院感染有关，尤其是在重症和ICU患者中。由DTR和PDR革兰氏阴性菌引起的感染的治疗选择极为有限，且基于病例报告和系列研究。本文讨论了目前关于DTR和PDR感染治疗的现有知识。综述的一个重点集中在挽救治疗、协同联合用药（双联和三联联合用药）以及根据病原体的最低抑菌浓度（MIC）调整的增加暴露方案。文中全面介绍了关于新型抗菌药物的现有数据，包括新型β-内酰胺-β-内酰胺酶抑制剂联合用药、头孢地尔以及依拉环素作为重症患者中针对DTR和PDR革兰氏阴性菌株的潜在药物。
