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11种联合方案对耐碳青霉烯类肠杆菌的体外联合药敏试验
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作者单位:

1.安徽医科大学第一附属医院 安徽省公共卫生临床中心检验科, 安徽 合肥 230000;2.安徽医科大学附属阜阳医院检验科, 安徽 阜阳 236000;3.安徽医科大学第二附属医院检验科, 安徽 合肥 230601

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通讯作者:

沈继录  E-mail: shenjilu@ahmu.edu.cn

中图分类号:

+2 R378]]>

基金项目:

安徽省教育厅2020年安徽省高校合作攻关和公共卫生协同创新项目（GXXT-2020-016）；阜阳市卫生健康委科研课题（FY2021-130）；安徽医科大学校基金资助项目（2022xkj215）


In vitro combined antimicrobial susceptibility test of 11 combined regimens against carbapenem-resistant Enterobacterales
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Affiliation:

1.Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University, Anhui Public Health Clinical Center, Hefei 230000, China;2.Department of Laboratory Medicine, Fuyang Hospital of Anhui Medical University, Fuyang 236000, China;3.Department of Laboratory Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China

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    摘要:

    目的 观察头孢他啶/阿维巴坦（CZA）联合氨曲南（ATM），亚胺培南（IPM）、美罗培南（MEM）分别联合头孢他啶（CAZ）、头孢哌酮/舒巴坦（SCF）、阿米卡星（AK）、左氧氟沙星（LEV）和磷霉素（FOS）对产KPC、NDM和IMP的耐碳青霉烯类肠杆菌（CRE）的体外联合药物敏感性。 方法 选取从临床标本中分离的38株非重复CRE，采用微量肉汤稀释法测定抗菌药物对菌株的最低抑菌浓度（MIC），棋盘稀释法进行联合药敏试验，计算部分抑菌浓度指数（FIC）判定联合效果。 结果 CZA对22株产KPC菌株的MIC均≤4 μg/mL，对16株产B类金属酶NDM、IMP菌株的MIC均>128 μg/mL，联合ATM后协同率为100%；IPM与MEM分别联合SCF协同率最强，分别为63.2%、68.4%，协同率与相加率之和为100%，IPM联合FOS的协同率与相加率之和最低，为40.5%。在肺炎克雷伯菌（KP）中，IPM与MEM联合SCF协同率均为68%，协同率与相加率之和均为100%，IPM联合FOS的协同率与相加率之和最低，为24%；大肠埃希菌（ECO）中，IPM与MEM联合SCF协同率分别为44.4%、77.8%，协同率与相加率之和为100%，IPM联合FOS的协同率与相加率之和最低，为66.7%。基因型KPC菌株中，IPM与MEM联合SCF协同率分别为72.7%、63.6%，协同率与相加率之和均为100%，IPM联合FOS的协同率与相加率之和最低，为22.7%；基因型NDM菌株中，IPM与MEM联合SCF协同率分别为46.7%、80.0%，协同率与相加率之和为100%，IPM联合FOS的协同率与相加率之和最低，为64.3%。所有联合方案均无拮抗作用。 结论 CZA单独或联合ATM对CRE菌株有效。IPM与MEM分别联合其他抗菌药物中，IPM与MEM联合SCF的协同率与相加率之和最高，IPM联合FOS的协同率与相加率之和最低。不是所有联合方案都有效，同一菌株不同联合方案的效果不同，同一联合方案对不同菌株效果也不同，两药间的剂量配比也很重要。

    Abstract:

    Objective To observe the in vitro susceptibility test result of ceftazidime/avibactam (CZA) combined with aztreonam (ATM), as well as imipenem (IPM) and meropenem (MEM) respectively combined with ceftazidime (CAZ), cefoperazone/sulbactam (SCF), amikacin (AK), levofloxacin (LEV) and fosfomycin (FOS) to KPC-, NDM- and IMP-producing carbapenem-resistant Enterobacterales (CRE). Methods 38 non-repetitive CRE strains were isolated from clinical specimens. The minimal inhibitory concentration (MIC) of antimicrobial agents against CRE strains was determined by micro-broth dilution method. Combined antimicrobial susceptibility test was performed by the chessboard dilution method. Fractional inhibitory concentration (FIC) index was calculated to determine the combined effect. Results The MICs of CZA to 22 KPC-producing strains were ≤ 4 μg/mL, to 16 class B metallo-enzyme(NDM and IMP)-producing strains were >128 μg/mL. The synergy rate of CZA was 100% after combined with ATM. The synergy rate of IPM or MEM combined with SCF was the highest, which were 63.2% and 68.4% respectively, and the sum of synergy rate and addition rate was 100%, while the sum of synergy rate and addition rate of IPM combined with FOS was the lowest (40.5%). Among Klebsiella pneumoniae (KP) strains, the synergy rates of IPM or MEM combined with SCF were both 68%, the sum of synergy rate and addition rate was 100%, the sum of synergy rate and addition rate of IPM combined with FOS was the lowest (24%). Among Escherichia coli (ECO), the synergy rates of IPM or MEM combined with SCF were 44.4% and 77.8% respectively, the sum of synergy rate and addition rate was 100%, the sum of synergy rate and addition rate of IPM combined with FOS was the lowest (66.7%). Among genotype KPC strains, the synergy rates of IPM or MEM combined with SCF were 72.7% and 63.6% respectively, the sum of synergy rate and addition rate was 100%, the sum of synergy rate and addition rate of IPM combined with FOS was the lowest (22.7%). Among genotype NDM strains, the synergy rates of IPM or MEM combined with SCF were 46.7% and 80.0% respectively, the sum of synergy rate and addition rate was 100%, the sum of synergy rate and addition rate of IPM combined with FOS was the lowest (64.3%). All combined schemes had no antagonistic effect. Conclusion CZA alone or in combination with ATM is effective for CRE strains. Among all the combinations of IPM and MEM respectively with other antimicrobial agents, the sum of synergy rate and addition rate of IPM and MEM combined with SCF is the highest, and the sum of synergy rate and addition rate of IPM combined with FOS is the lowest. Not all combination schemes are effective. The effect of different combination schemes on the same strain is different, and the effect of the same combination scheme on different strains is also different. The dose ratio between two agents is also important.

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陆国平,唐浩,夏兆新,等.11种联合方案对耐碳青霉烯类肠杆菌的体外联合药敏试验[J]. 中国感染控制杂志,2023,(3):287-294. DOI:10.12138/j. issn.1671-9638.20233384.
Guo-ping LU, Hao TANG, Zhao-xin XIA, et al.In vitro combined antimicrobial susceptibility test of 11 combined regimens against carbapenem-resistant Enterobacterales[J]. Chin J Infect Control, 2023,(3):287-294. DOI:10.12138/j. issn.1671-9638.20233384.

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  • 收稿日期:2022-09-19
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  • 在线发布日期: 2024-04-28
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