亚胺培南/瑞来巴坦与阿米卡星联合对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性  

In vitro antibacterial activity of imipenem-relebactam combined with amikacin against carbapenem-resistant Klebsiella pneumoniae

作　　者：赵慧珺 马琳[2] 刘长鑫 张侃 郭桦 丁俊谕 刘琪琦[3] 管希周[2] ZHAO Hui-jun;MA Lin;LIU Chang-xin;ZHANG Kan;GUO Hua;DING Jun-yu;LIU Qi-qi;GUAN Xi-zhou(Chinese PLA Medical School,Beijing 100853,China;不详)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第八医学中心呼吸与危重症医学部,北京100091 [3]军事医学科学院军事医学研究院生物信息中心,北京100850

出　　处：《中华医院感染学杂志》2023年第12期1788-1794,共7页Chinese Journal of Nosocomiology

基　　金：工业和信息化部科技司基金资助项目(2020-0103-3-1-5)。

摘　　要：目的 本研究旨在探讨新型β-内酰胺酶抑制剂亚胺培南/瑞来巴坦(IMR)单独和与阿米卡星(AMK)联合对耐碳青霉烯类肺炎克雷伯菌(CRKP)的体外抗菌活性。方法 收集中国人民解放军总医院2017-2018年间,临床分离的30株非重复CRKP菌株,使用Illumina高通量测序仪Hiseq 2500型进行二代测序,之后将其序列进行拼接、组装并加以注释,最后通过多位点序列分型(MLST)分析,确定菌株的分子分型。采用微量肉汤稀释法测定IMR和AMK的最小抑菌浓度(MIC),棋盘法测定IMR和AMK的联合抑菌效应,并利用部分抑菌浓度指数(FICI)和Loewe加性指数评估联合抑菌效果。结果 基因测序结果显示CRKP菌株均携带碳青霉烯酶,其中携带KPC-1 21株,携带OXA-48 5株,携带NDM-1 2株,携带NDM-5和OXA-10各1株。另外,β-内酰胺酶中SHV-134(19/30,63.33%),TEM-181(17/30,56.67%)和CTX-M-65(15/30,50.00%)分布广泛。MLST将30株CRKP菌株分为9个不同的ST型,以ST11和ST383为主。30株CRKP菌株对IMR的耐药率为56.67%(17/30),对21株CRKP菌株联合AMK后测得IMR的MIC_(50)和MIC_(90)由联合之前的128μg/ml均下降至0.5μg/ml,对产金属酶(MBLs)和非产MBLs的CRKP菌株的MIC值最高均降低1/256(P<0.05);FICI评估作用显示,14株(14/21,66.67%)为协同作用,7株(7/21,33.33%)为无关作用;Loewe加性指数评估显示19株(19/21,90.48%)为协同作用,2株(2/21,9.52%)为相加作用,两种评估方法均未出现拮抗作用。结论 IMR联合AMK对CRKP菌株有较好的体外协同抗菌作用,可成为治疗IMR耐药及MBLs细菌的潜在药物组合。OBJECTIVE To investigate the in vitro antibacterial activity of a novel β-lactam/β-lactamase inhibitor imipenem/relebactam(IMR) alone and combined with amikacin(AMK) against carbapenem-resistant Klebsiella pneumoniae(CRKP).METHODS Totally 30 strains of non-repeating CRKP clinically isolated from Chinese PLA general hospital during 2017-2018 were collected and sequenced by Illumina high-throughput sequencer,Hiseq 2500,after which,the sequences were stitched,assembled and annotated,and finally the molecular typing of these strains was determined by multi-locus sequence typing(MLST) analysis.The micro broth dilution method was used to determine the minimum inhibitory concentration(MIC) of IMR and AMK.The checkerboard method was used to determine the synergistic effect of IMR and AMK.The paractional inhibitory concentration index(FICI) and Loewe additivity index were used to evaluate the inhibitory effect of the combination.RESULTS Gene sequencing showed that all CRKP strains carried carbapenemase,including 21 strains carrying the KPC-1,5 strains carrying the OXA-48,2 strains carrying the NDM-1,and 1 strain each carrying NDM-5 and OXA-10.In addition,SHV-134(19/30,63.33%),TEM-181(17/30,56.67%) and CTX-M-65(15/30,50.00%) were widely distributed among β-lactamases.30 CRKP strains were divided into 9 different ST types by MLST,mainly ST11 and ST383.The drug resistance rate of 30 CRKP strains to IMR was 56.67%(17/30).The MIC50 and MIC90 of IMR decreased from 128 μg/mL before combination to 0.5 μg/ml for 21 CRKP strains in combination with AMK.A maximum reduction in MIC values of 1/256(P<0.05) for both MBLs-producing CRKP stains and non-MBLs-producing strains of CRKP.FICI assessment showed 14 strains(14/21,66.67%) were synergistic and 7 strains(7/21,33.33%) were not.Loewe additivity index assessment showed that 19 strains(19/21,90.48%) were synergistic,and 2 strains(2/21,9.52%) were additive,with no antagonistic effects in either assessment method.CONCLUSION IMR combined with AMK had an excellent synergistic antibacte

关 键 词：耐碳青霉烯类肺炎克雷伯菌 亚胺培南/瑞来巴坦 阿米卡星 协同作用 多位点序列分型 

分 类 号：R378[医药卫生—病原生物学]