头孢他啶/阿维巴坦与氨曲南联合对临床分离碳青霉烯耐药肺炎克雷伯菌的协同作用

Synergistic effect of ceftazidime/avicarbam combined with aztreonam against carbapenem-resistant Klebsiella pneumoniae isolates

目的探讨头孢他啶/阿维巴坦与氨曲南联合对碳青霉烯耐药肺炎克雷伯菌的协同作用。方法采用琼脂平板倍比稀释法测定细菌的最低抑菌浓度,PCR扩增碳青霉烯酶基因和超广谱β-内酰胺酶基因,RT-PCR检测碳青霉烯酶基因的表达量,多位点序列分型分析菌株的基因型,棋盘法测定头孢他啶/阿维巴坦与氨曲南的协同作用。结果10株碳青霉烯高耐药菌株除对替加环素敏感性较高外,对其他实验药物均具有较高的耐药性。β-内酰胺酶基因NDM、CTX-M和SHV在菌株中分布广泛,且对碳青霉烯耐药高的菌株其碳青霉烯酶基因表达也较高(r=0.805,P=0.029)。菌株共有4个ST型,ST11是最流行的基因型,NDM基因存在于3种不同的基因型菌株中。头孢他啶/阿维巴坦与氨曲南联合对7株碳青霉烯耐药肺炎克雷伯菌具有协同作用,3株为无关作用。结论碳青霉烯耐药肺炎克雷伯菌的高耐药与其携带的耐药基因相关,头孢他啶/阿维巴坦与氨曲南有较高的协同作用。

Objective To explore the synergistic effect of ceftazidime/avicarbam combined with aztreonam against carbapenem-resistant isolates of Klebsiella pneumoniae(CRKP).Methods We collected 10 clinical isolates of CRKP from our hospital and determined the minimal inhibitory concentrations of the commonly used antibiotics in these isolates using agar plate double-dilution method.The carbapenemase genes and extended-spectrumβ-lactamase genes of the bacteria were amplified by PCR,and the expression of carbapenemase genes was detected by RT-PCR.The bacterial genotypes were analyzed with multilocus sequence typing.The synergistic effect of ceftazidime/avicarbam combined with aztreonam against these CRKP isolates was determined using the checkerboard method.Results The 10 CRKP isolates were all sensitive to tigecycline but highly resistant to all the other antibiotics tested.Theβ-lactamase genes(NDM,CTX-M and SHV)were widely distributed in these isolates,and the strains with a high resistance to carbapenem also had high expression levels of carbapenemase genes(r=0.805,P=0.029).Four distinct ST genotypes were identified among the CRKP strains,and the genotype ST11 had the highest epidemic potential;NDM gene was present in the strains of 3 different ST genotypes.Ceftazidime/avicarbam combined with aztreonam showed a synergistic inhibitory effect in 7 CRKP strains and produced irrelevant effects in the other 3 strains.Conclusion The high resistance of CRKP strains can be attributed to the resistance genes they carry,and the combination of ceftazidime/avicarbam and aztreonam can produce a strong synergistic inhibitory effect in these strains.