Subdirección Académica de Químico Farmacéutico Biólogo, Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.
Instituto de Patología Infecciosa y Experimental "Dr. Francisco Ruiz Sánchez", Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.
Front Cell Infect Microbiol. 2022 May 20;12:884365. doi: 10.3389/fcimb.2022.884365. eCollection 2022.
Infections by Gram-negative multi-drug resistant (MDR) bacterial species are difficult to treat using available antibiotics. Overuse of carbapenems has contributed to widespread resistance to these antibiotics; as a result, carbapenem-resistant Enterobacterales (CRE), (CRAB), and (CRPA) have become common causes of healthcare-associated infections. Carbapenems, tigecycline, and colistin are the last resource antibiotics currently used; however, multiple reports of resistance to these antimicrobial agents have been documented worldwide. Recently, new antibiotics have been evaluated against Gram-negatives, including plazomicin (a new aminoglycoside) to treat CRE infection, eravacycline (a novel tetracycline) with activity against CRAB, and cefiderocol (a synthetic conjugate) for the treatment of nosocomial pneumonia by carbapenem-non-susceptible Gram-negative isolates. Furthermore, combinations of known β-lactams with recently developed β-lactam inhibitors, such as ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime-tazobactam, and meropenem-vaborbactam, has been suggested for the treatment of infections by extended-spectrum β-lactamases, carbapenemases, and AmpC producer bacteria. Nonetheless, they are not active against all carbapenemases, and there are reports of resistance to these combinations in clinical isolates.This review summarizes and discusses the and clinical evidence of the recently approved antibiotics, β-lactam inhibitors, and those in advanced phases of development for treating MDR infections caused by Gram-negative multi-drug resistant (MDR) bacterial species.
革兰氏阴性多重耐药（MDR）细菌感染用现有抗生素治疗较为困难。碳青霉烯类抗生素的过度使用导致了这些抗生素的广泛耐药；因此，耐碳青霉烯肠杆菌科（CRE）、耐碳青霉烯鲍曼不动杆菌（CRAB）和耐碳青霉烯铜绿假单胞菌（CRPA）已成为常见的医疗保健相关感染的原因。碳青霉烯类、替加环素和黏菌素是目前使用的最后一类抗生素；然而，世界各地已记录到多份这些抗菌药物耐药的报告。最近，已评估了一些针对革兰氏阴性菌的新抗生素，包括治疗 CRE 感染的新型氨基糖苷类药物-plazomicin、对 CRAB 具有活性的新型四环素类药物-eravacycline 以及治疗耐碳青霉烯类革兰氏阴性菌引起的医院获得性肺炎的合成偶联物-cefiderocol。此外，还提出了使用已知β-内酰胺类药物与最近开发的β-内酰胺抑制剂的组合，如头孢他啶-阿维巴坦、头孢洛扎-他唑巴坦、头孢他啶-他唑巴坦和美罗培南-沃巴坦，用于治疗产超广谱β-内酰胺酶、碳青霉烯酶和 AmpC 产酶菌引起的感染。然而，它们对所有碳青霉烯酶都没有活性，并且在临床分离株中已有这些组合耐药的报道。本综述总结并讨论了最近批准的抗生素、β-内酰胺抑制剂以及处于开发后期阶段的治疗革兰氏阴性多重耐药（MDR）细菌感染的抗生素的作用机制和临床证据。
