替加环素与临床常用抗菌药物对碳青霉烯类耐药肠杆菌科细菌的协同作用研究

The synergy of tigecycline with commonly used antibiotics against carbapenemresistant Enterobacteriaceae

目的评价替加环素与临床常用抗菌药物对碳青霉烯类耐药肠杆菌科细菌(CRE)的协同作用。方法收集2014—2016年临床分离的非重复CRE共235株。琼脂稀释法进行药物敏感性试验并分析替加环素和9种常用抗菌药物的耐药率。选取替加环素非敏感的35株作为研究对象,并采用棋盘稀释法检测替加环素联合其他9种抗菌药物(亚胺培南、美罗培南、头孢他啶、头孢噻肟、氨曲南、左氧氟沙星、阿米卡星、哌拉西林/三唑巴坦和头孢哌酮/舒巴坦)对CRE的协同作用。结果肺炎克雷伯菌、沙雷菌属、产气肠杆菌、阴沟肠杆菌对替加环素的耐药率较高,分别是5.1%(7/137)、5.6%(1/18)、7.7%(1/13)和8.3%(1/12)。替加环素与头孢他啶、哌拉西林/三唑巴坦联合效果最明显,协同百分比都是28.6%(10/35)。替加环素与头孢噻肟(9/35,25.7%)、左氧氟沙星(8/35,22.9%)和头孢哌酮/舒巴坦(7/35,20.0%)也显示出较好的协同作用。研究中未出现药物拮抗的作用。结论替加环素与头孢他啶、哌拉西林/三唑巴坦联合对CRE的协同作用比较明显。替加环素的联合治疗可能比单用更为有效。

Objective To investigate the synergy effects of tigecy cline combind with commonly used other antibacterial agents against the carbapenem-resistant Enterobacteriaceae （CRE）. Methods A total of 235 non- repetitive CRE collected from clinical isolates in 2014 to 2016. The antimicrobial susceptibility of tigecycline and 9 kinds of commonly used antibacterial agents were determined by the ager dilution method. The 35 strains that were not sensitive to tigecycline were studied. Synergistic effects between tigecycline and other antibacterial agents, including irnipenem, meropenem, ceftazidime, cefotaxime, levofloxacin, piperacillin/tazobactam, amikacin, aztreonam, and cefoperazone/sulbactam against 35 strains of CRE were determined by the chequerboard assay. Results The drug- resistant rates of tigecycline were 5.1% （7/137） in Klebsiella pneumonia, 5.6% （1/18） in serratia, 7.7% （1/13） in Enterobacter aerogenes, 8.3% （1/12） in Enterobacter cloacae. Tigecycline in combination with ceftazidime and piperacillin/tazobactam showed the best activity against CRE with synergy rate of 28.6% （10/35）. Tigecycline in combination with cefotaxime（9/35, 25.7%）, levofloxacin（8/35, 22.9%） and cefoperazone/sulbactam （7/35, 20.0%） also prsesnted good activity against CRE. No antagonism was demonstrated among all of combinations. Conclusion A combination of tigecycline and ceftazidime or piperacillin/tazobactam shows good activity, combined treatments may be more effective than tigecycline alone. It provides a new strategy in the campaign against serious infections caused by CRE.