碳青霉烯类耐药肠杆菌目细菌基因型及联合药敏试验

Genotypes of carbapenem-resistant Enterobacterales and comined antimicrobial sensitivity testing

    摘要
  • 摘要:
    目的 分析碳青霉烯类耐药肠杆菌目细菌(CRE)的碳青霉烯酶基因型分布特征，评价7组联合药敏方案对CRE的体外抗菌效果，为临床抗感染治疗提供实验依据。
    方法 收集2021年1月-2025年6月新疆四七四医院临床分离的88株成人非重复CRE菌株，采用胶体金免疫层析法检测碳青霉烯酶基因型；通过肉汤微量稀释棋盘法测定多黏菌素B(PB)单药及PB联合亚胺培南(IPM)、美罗培南(MEM)、磷霉素(FOS)、阿米卡星(AK)、环丙沙星(CIP)、替加环素(TGC)6种药物，以及氨曲南联合头孢他啶/阿维巴坦(ATM+CZA)的最低抑菌浓度(MIC)，计算部分抑菌浓度指数(FIC)评价联合效应。
    结果 88株CRE中，KPC型占68.18%(60/88)，NDM型占30.68%(27/88)，1株未检出。碳青霉烯类耐药肺炎克雷伯菌(CRKP)以KPC型为主(96.55%)，碳青霉烯类耐药大肠埃希菌(CREC)、阴沟肠杆菌(CRECL)以NDM型为主(90.00%、80.00%)。联合用药MIC值较单药降低(P <0.05)，ATM+CZA协同效应最优，PB+CIP效应最弱。KPC型菌株中PB+FOS协同累积效应最高，NDM型菌株中ATM+CZA协同累积效应最高；PB+IPM、PB+MEM在两类基因型中均呈良好相加作用。
    结论 CRE主要携带KPC、NDM型碳青霉烯酶，不同菌种基因型差异显著。联合用药可有效降低MIC值及耐药率，建议根据CRE基因型选择个体化联合治疗方案。

     

    Abstract:
    OBJECTIVE To analyze the distribution characteristics of carbapenemase genotypes in carbapenem-resistant Enterobacterales (CRE) and evaluate the in vitro antibacterial effects of seven combined antimicrobial susceptibility testing regimens against CRE, providing experimental evidence for clinical anti-infection treatment.
    METHODS A total of 88 non-repetitive adult CRE strains isolated clinically from Xinjiang 474 Hospital from Jan. 2021 to Jun. 2025 were collected. The carbapenemase genotypes were detected with a colloidal gold immunochromatographic assay. The minimum inhibitory concentration (MIC) of polymyxin B (PB) alone and PB combined with six drugs, namely imipenem (IPM), meropenem (MEM), fosfomycin (FOS), amikacin (AK), ciprofloxacin (CIP) and tigecycline (TGC), as well as aztreonam combined with ceftazidime/avibactam (ATM+CZA), were determined with the broth microdilution checkerboard method. The fractional inhibitory concentration index (FIC) was calculated to evaluate the combined effects.
    RESULTS Among the 88 CRE strains, 68.18% (60/88) were KPC-type, 30.68% (27/88) were NDM-type, and one strain was undetected. Carbapenem-resistant Klebsiella pneumoniae (CRKP) was predominantly KPC-type (96.55%), while carbapenem-resistant Escherichia coli (CREC) and Enterobacter cloacae (CRECL) were predominantly NDM-type (90.00%, 80.00%, respectively). The MIC values of combined drug therapy were lower than those of single drug therapy (P < 0.05). ATM+CZA exhibited the best synergistic effect, while PB+CIP had the weakest effect. Among KPC-type strains, PB+FOS showed the highest cumulative synergistic effect, while among NDM-type strains, ATM+CZA had the highest cumulative synergistic effect. PB+IPM and PB+MEM demonstrated good additive effects in both genotypes.
    CONCLUSIONS CRE mainly carries KPC and NDM-type carbapenemases, with significant differences in genotypes among different bacterial species. Combined drug therapy can effectively reduce MIC values and resistance rates. It is recommended to select individualized combined treatment regimens based on the CRE genotype.

     

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