碳青霉烯类抗菌药物对大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌的防突变浓度研究

Mutant preventing concentrations of carbapenem antibiotics against Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Acinetobacter Bauman

目的：探索碳青霉烯类抗菌药物对临床分离的100株大肠埃希菌、肺炎克雷伯菌β-内酰胺酶表型和铜绿假单胞菌、鲍曼不动杆菌的防突变浓度（MPC）。方法：采用琼脂稀释法测定碳青霉烯类（亚胺培南、美洛培南、厄他培南和多利培南）对临床分离的革兰阴性耐药菌株的最低抑菌浓度（MIC）及MPC并计算MPC/MIC比值。采用WHONET5.6及SPASS13.0进行分析。结果：肠杆菌科细菌和鲍曼不动杆菌的MPC/MIC比值为2~4,铜绿假单胞菌为4-≥16。β-内酰胺酶阳性的肺炎克雷伯菌、大肠埃希菌MPC/MIC比值高于β-内酰胺酶阴性菌株（4至〉16μg·mL-1）。结论：基于MPC的碳青霉烯类抗菌药物可以通过MPC/MIC比值调整给药剂量,降低耐药菌株的总体数量和感染负荷,抑制耐药菌突变体的选择性富集扩增。

OBJECTIVE To explore mutant preventing concentrations （MPC） of carbapenem antibiotics against clinical iso- lates of 100 strains of Escherichia coli, Klebsiella pneumoniae ESBLs phenotype, Pseudomonas aeruginosa and Acinetohacter Bauman. METItODS Minimal inhibitory concentration （MIC） and MPC of carhapenems （imipenem, meropenem and ertapen- em, doripenem） were determined using agar dilution method for gram negative strains of clinical isolates to calculate the ratio of MPC/MIC. WHONET 5.6 and SPASS 13.0 were used for analysis. RESULTS Real ratios of MPC/MIC were 2 - 4 for Enter- ohacteriaceae coli and Acinetohacter Bauman, and 4 - ≥ 16 for Pseudomonas aeruginosa. Beta lactamase positive Klebsiella pneumoniae and Escheriehia coli had higher MPC/MIC ratios than those for beta lactamase negative strains （4 to 〉16 g·mL-1 ）. CONCLUSION Carhapenem antibiotics based on MPC can adjust dose according to MPC/MIC ratios, reduce total quantity and burden of infection resistant strains, inhibit selective enrichment and amplification of mutant resistant bacteria.