Sheu Chau-Chyun, Chang Ya-Ting, Lin Shang-Yi, Chen Yen-Hsu, Hsueh Po-Ren
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
School of Medicine, Sepsis Research Institute, Graduate Institute of Medicine, Graduate Institute of Clinical Medicine, Center of Dengue Fever Control and Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Front Microbiol. 2019 Jan 30;10:80. doi: 10.3389/fmicb.2019.00080. eCollection 2019.
Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with activity against CRE; and eravacycline, which is a tetracycline class antibacterial with activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new β-lactam/β-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE.
碳青霉烯类抗生素被视为治疗多重耐药革兰氏阴性菌感染的最后一道防线。随着碳青霉烯类抗生素在临床实践中的使用日益增加，耐碳青霉烯病原体的出现如今对人类健康构成了巨大威胁。目前，治疗耐碳青霉烯肠杆菌科细菌（CRE）感染的抗生素选择非常有限，主要治疗药物为多粘菌素、替加环素、磷霉素和氨基糖苷类。迫切需要新的有效抗CRE治疗方法。在此，我们描述了目前对与CRE相关问题的认识，并综述了CRE感染的联合治疗策略，包括高剂量替加环素、高剂量延长输注碳青霉烯类以及双联碳青霉烯治疗。我们还综述了未来可能用于治疗CRE感染的新型抗生素：对产KPC酶和OXA-48酶的菌株有效的头孢他啶/阿维巴坦；对产KPC酶的菌株有效的美罗培南/法硼巴坦；对CRE有活性的新一代氨基糖苷类药物普拉唑米星；以及对CRE有活性的四环素类抗菌药物依拉环素。尽管仍缺乏针对CRE治疗的直接证据，且耐药性的产生令人担忧，但这些新型抗生素为CRE感染提供了更多治疗选择。最后，我们综述了其他正在研发的潜在抗CRE抗生素：亚胺培南/瑞来巴坦和头孢地尔。目前，对于严重的CRE感染，应考虑采用高剂量及可能包括新型β-内酰胺/β-内酰胺酶抑制剂的联合策略，以最大限度提高治疗成功率。未来，当有更多治疗选择时，CRE感染的治疗应个体化，并基于耐药分子表型、药敏谱、疾病严重程度和患者特征。需要更多高质量研究来指导CRE感染的有效治疗。
