替加环素联合9种抗菌药物对碳青霉烯耐药细菌的抗菌作用

Synergy activity of tigecycline combined with other nine antimicrobials against carbapenem-resistant pathogens

目的评价替加环素与9种抗生素联合对替加环素耐药的耐碳青霉烯酶细菌的抗菌效果。方法收集2016年住院患者的碳青霉烯类耐药菌株,采用飞行时间质谱仪进行菌株鉴定,PCR扩增及序列分析耐药基因,微量棋盘稀释法测定替加环素与9种抗生素的联合药敏试验。结果对于耐碳青霉烯酶肠杆菌科细菌,替加环素与哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、左氧氟沙星、莫西沙星、阿米卡星和头孢他啶等药物联合显示较好的协同或者相加作用;对于耐碳青霉烯酶鲍曼不动杆菌,替加环素与亚胺培南、美罗培南、阿莫西林/克拉维酸和头孢他啶等药物联合显示较好的协同或者相加作用;尚未发现存在拮抗作用。结论替加环素与临床常见抗生素联合均呈现较好效果,可为临床治疗由替加环素耐药的耐碳青霉烯酶细菌引起的严重感染提供新思路。

Objective To evaluate the synergy effect of tigecycline with other 9 antibacterials against clinical isolates of carbapenem-resistant Enterobacteriaceae（ CRE） and carbapenem-resistant A. baumannii（ CRAB） which was resistant to tigecycline. Methods The carbapenem-resistant bacteria collected in 2016 were identified by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry（ MALDI-TOFMS）. The carbapenemase genes were determined by Polymerase chain reaction（ PCR）. Nine antibiotics in combination with tigecycline were examined by chequerboard assay. Results Synergy or additive activity was demonstrated for piperacillin-tazobactam,cefoperazone-sulbactam,levofloxacin,moxifloxacin,amikacin and ceftazidime in combination with tigecycline against CRE isolates. Moreover,synergy or additive activity was demonstrated for imipenem,meropenem,amoxicillin-clavulanic acid and ceftazidime in combination with tigecycline against CRAB strains. Antagonism was not observed. Conclusion The findings from this study indicate that there is great potential of antibiotic combinations against carbapenem-resistant Gram-negative pathogens which were resistant to tigecycline,opening the way to a more rationale clinical assessment of novel combination therapies to combat infections caused by CRE and CRAB.