阿维巴坦联合头孢他啶、氨曲南或美罗培南对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性

In vitro antimicrobial activity of avibactam in combination with ceftazidime,aztreonam or meropenem against carbapenem-resistant Klebsiella pneumoniae

目的研究阿维巴坦(固定浓度为4μg/mL)联合β-内酰胺类抗生素对耐碳青霉烯类肺炎克雷伯菌(CRKP)的体外抗菌活性。方法收集某院临床分离的非重复CRKP,采用微量肉汤稀释法测定头孢他啶/阿维巴坦、氨曲南/阿维巴坦、美罗培南/阿维巴坦对CRKP的最低抑菌浓度(MIC)和最低杀菌浓度(MBC),采用聚合酶链反应(PCR)方法测定碳青霉烯酶等耐药基因。结果63株CRKP菌株,57株携带blaKPC基因,5株携带金属酶基因,1株未检出常见碳青霉烯酶耐药基因。57株blaKPC基因阳性的CRKP菌株,头孢他啶/阿维巴坦、氨曲南/阿维巴坦、美罗培南/阿维巴坦对其MIC均分别≤8/4、4/4、0.5/4μg/mL,阿维巴坦使头孢他啶、氨曲南及美罗培南对其MIC50及MIC90值明显下降。5株金属酶基因阳性的CRKP菌株,阿维巴坦未使头孢他啶、美罗培南MIC90值有所下降,但阿维巴坦可使氨曲南MIC90下降达99.8%。三种阿维巴坦的复方制剂对63株CRKP的MBC50值与MIC50值相同,其MBC90值与MIC90值相同。结论阿维巴坦与三种常见β-内酰胺类抗生素(头孢他啶、氨曲南、美罗培南)联合对表达KPC-2型碳青霉烯酶的CRKP菌株具有较好的抗菌效果,与头孢他啶或美罗培南联合对携带金属酶的CRKP菌株无抑制作用,但联合氨曲南对携带金属酶的CRKP菌株具有较好的抗菌效果。

Objective To study in vitro antimicrobial activity of combination of avibatam(fixed concentration of 4μg/mL)andβ-lactam antibiotics against carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods Non-repetitive CRKP strains isolated from a hospital were collected,minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of ceftazidime/avibatam,aztreonam/avibatam,and meropenem/avibatam against CRKP was detected with broth microdilution method,carbapenemase resistance genes were determined by polymerase chain reaction(PCR).Results Among 63 CRKP strains,57 strains harbored blaKPC gene,5 strains harbored metalloenzyme gene,and 1 strain did not found common carbapenem-resistant gene.Among 57 CRKP strains with positive blaKPC gene,MICs of ceftazidime/avibatam,aztreonam/avibatam,and meropenem/avibatam were≤8/4,4/4,and 0.5/4μg/mL respectively,avibatam significantly decreased the MIC50 and MIC90 values of ceftazidime,aztreonam and meropenem.Among 5 CRKP strains with positive metalloenzyme gene,avibatam did not decrese MIC90 of ceftazidime and meropenem,but decreased MIC90 of aztreonam by 99.8%,MBC50 and MIC50 of three compound of avibatam against 63 strains of CRKP were identical,their MBC90 and MIC90 were identical.Conclusion Combination of avibatam with three commonβ-lactam antibiotics(ceftazidime,aztreonam and meropenem)has a good antimicrobial effect on CRKP strains expressing KPC-2 carbapenemase,combination with ceftazidime or meropenem has no inhibitory effect on metalloenzyme-harboring CRKP strains,but combination with aztreonam has a good antimicrobial effect on metalloenzyme-harboring CRKP strains.