碳青霉烯类抗生素耐药肠杆菌科细菌感染的治疗策略
Antimicrobial treatment of carbapenem-resistant Enterobacteriaceae infections
摘要碳青霉烯类抗生素耐药肠杆菌科细菌(CRE)已成为临床感染的重要威胁,主要引起院内获得性感染,抗菌治疗可选择药物少。目前国际上对CRE治疗的主要药物为多黏菌素、替加环素、头孢他啶-阿维巴坦、磷霉素及氨基糖苷类抗生素等。多黏菌素和替加环素对CRE体外敏感性高,不受细菌产生碳青霉烯酶类型的影响。多黏菌素因为存在异质性耐药,并且剂量与肾毒性呈正相关,临床常选择合适剂量,同时联合其他抗菌药物使用。常规剂量替加环素在包括血流、肺泡衬液等部位难以达到足够浓度,常需加大剂量并联合其他药物使用。头孢他啶-阿维巴坦对产金属酶的CRE缺乏有效抗菌活性,可作为非产金属酶CRE感染治疗的重要选择。CRE最常见的定植部位是患者的胃肠道。若患者合并肠道黏膜破坏及免疫功能下降,CRE可由肠道入血引起持续性菌血症。
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abstractsCarbapenem-resistant Enterobacteriaceae (CRE) mainly cause hospital-acquired infections, which have become an major threat in clinical practice and there are few antibacterial drugs available for CRE infection. At present, the main drugs for CRE treatment are polymyxin, tigecycline, ceftazidime-avibactam, fosfomycin and aminoglycoside antibiotics. Polymyxin and tigecycline are highly sensitive to CRE in vitro and are not affected by the type of carbapenemase produced by bacteria. Due to heterogeneous resistance and dose-related nephrotoxicity, polymyxin is often used in combination with other antibiotics. Tigecycline is difficult to reach sufficient concentrations in blood and alveolar lining fluid when using conventional dose. Therefore, it is necessary to increase the dose or to be used in combination with other drugs. Ceftazidime-avibactam lacks effective antibacterial activity against metalloenzyme-producing CRE, which can be used for the treatment of non metalloenzyme-producing CRE infection. The most common site of CRE colonization is the gastrointestinal tract. If the patient have intestinal mucosal destruction and decreased immune function, CRE can cause persistent bacteremia from intestinal blood.
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