Colistin联合其它抗菌药物对碳青霉烯耐药肺炎克雷伯的体外抗菌活性研究
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- 英文论文题名：In vitro Activities of Colistin in Combination with other antimicrobials against Carbapenem-Resistant Klebsiella Pneumoniae
- 论文作者：白艳 ; 柴栋 ; 王瑾 ; 王睿
- 年：2016
- 作者机构：中国人民解放军总医院药物保障中心;中国人民解放军总医院药物临床研究中心;
- 论文关键词：多粘菌素E ; 联合 ; 抗菌药物 ; 耐碳青霉烯肺炎克雷伯 ; 体外抗菌活性
- 英文论文关键词：Colistin ; Combination ; Antibacterial ; Carbapenem-resistant Klebaiella-pneumoniae ; Synergistic antibacterial activity
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：中文
- 分类号：R96
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：10
- 文件大小：838k
- 原文格式：O
- 会议级别：全国
摘要
目的:测定17种不同抗菌药物对135株碳青霉烯耐药肺炎克雷伯菌(Carbapenem resistant Klebaiella pneumoniae,CRKP)的最低抑菌浓度,评价CRKP菌株药物敏感性。评价以Colistin为基础联合比阿培南、头孢他啶-阿维巴坦2种联合用药方案对CRKP的协同抗菌活性,为临床用药选择提供理论依据。方法:(1)采用琼脂平板法测定135株CRKP对17种抗菌药物的MIC。(2)应用棋盘法设计,采用微量肉汤稀释法,测定135株CRKP对Colistin联合比阿培南和头孢他啶/阿维巴坦的联合MIC,再计算联合抑菌指数(Fraction Inhibitory Concentration Index,FICI),判定任一两药的联合体外抗菌活性。结果:(1)135株CRKP对17种抗菌药物中的氨曲南、他唑巴坦、头孢噻肟和舒巴坦已全部耐药(135株,100.0%),而对头孢哌酮/舒巴坦、头孢他啶、比阿培南、亚胺培南、美罗培南、左氧氟沙星的耐药率也达90%以上,仅有米诺环素、替加环素、头孢他啶/阿维巴坦和Colistin的敏感率达40%以上,根据MDR定义,共有130株为MDR-KP,达到了96.3%(130/135)。(2)多黏菌素E分别与比阿培南、头孢他啶/阿维巴坦联合应用时,135株CRKP的FICI分布分别为:FICI≤0.5占15.56%和4.45%;0.54的菌株。结论:(1)135株CRKP菌株的耐药形式严峻,95%以上为MDR-KP,几乎没有一种抗菌药物可以对所有菌株100%,应加强医院感控防治措施,严格抗菌药物管理和使用原则。(2)Colistin分别与比阿培南和头孢他啶/阿维巴坦的2种联合用药方案对CRKP的体外抗菌活性均以协同和部分协同作用为主,未发现拮抗作用。
Objective:To determine the minimum inhibitory concentration of 17 different antimicrobial agents against 135 strains of carbapenem resistant Klebsiella pneumoniae(CRKP),and to evaluate the susceptibility and the relationship between the synergistic antibacterial activity.To evaluate synergistic antimicrobial activity about polymyxin combined with biapenem、ceftazidime-Avibatam,so as to provide a theoretical basis for clinical treatment.Method:(1) The standard agar dilution method was used to determined MIC of 17 antimicrobial agents against 135 strains of CRKP.(2) The board design and micro broth dilution method was used to detected combination MIC of colistin combined with biapenenu ceftazidime / Avibatan,then calculate FIC,to determine combination antibacterial activity in vitro.Result:(1)135 strains of CRKP were all resistant to aztreonam,tazobactam,cefotaxime and sulbactam in 17 kinds of antibiotics,and resistant rate cefoperazone / shubatan,ceftazidime,biapenem,imipenem,meropenem,and levofloxacin was more than 90%,only sensitive rates of minocyline and tigecycline,ceftazidime / Avi Batan and polymyxin were more than 40%.According to the definition of MDR,a total of 130 strains were MDR-KP,reaching 96.3%(130/135).(2)When colistin was combined with biapenem and ceftazidime/Avi Batan respectively,the FICI results were as followed:FICI<0.5 accounted for 15.56%and 4.45%;0.54 was found.Conclusion:(1)135 CRKP strains were resistant to severe form,more than 95%of MDR-KP,almost no one kind of antibacterial drugs can be 100%of all strains,the hospital should strengthen the prevention and control measures,stricter management and the usage of antimicrobial drugs.(2) Colistin respectively combined with biapenem and ceftazidime/Avibatam,the in vitro antibacterial activity of CRKP are mainly synergy or partial synergy,and no antagonism is found.
Objective:To determine the minimum inhibitory concentration of 17 different antimicrobial agents against 135 strains of carbapenem resistant Klebsiella pneumoniae(CRKP),and to evaluate the susceptibility and the relationship between the synergistic antibacterial activity.To evaluate synergistic antimicrobial activity about polymyxin combined with biapenem、ceftazidime-Avibatam,so as to provide a theoretical basis for clinical treatment.Method:(1) The standard agar dilution method was used to determined MIC of 17 antimicrobial agents against 135 strains of CRKP.(2) The board design and micro broth dilution method was used to detected combination MIC of colistin combined with biapenenu ceftazidime / Avibatan,then calculate FIC,to determine combination antibacterial activity in vitro.Result:(1)135 strains of CRKP were all resistant to aztreonam,tazobactam,cefotaxime and sulbactam in 17 kinds of antibiotics,and resistant rate cefoperazone / shubatan,ceftazidime,biapenem,imipenem,meropenem,and levofloxacin was more than 90%,only sensitive rates of minocyline and tigecycline,ceftazidime / Avi Batan and polymyxin were more than 40%.According to the definition of MDR,a total of 130 strains were MDR-KP,reaching 96.3%(130/135).(2)When colistin was combined with biapenem and ceftazidime/Avi Batan respectively,the FICI results were as followed:FICI<0.5 accounted for 15.56%and 4.45%;0.5
引文
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13.朱亚萍,刘荣玉.肺炎克雷伯杆菌耐碳青霉烯类的机制及其防治[J].国际呼吸杂志2011,31(2):125-128.
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19.Li J,Learoyd M,Qiu F,et al A Randomized,Phase I Study to Assess the Safety,Tolerability and Pharmacokinetics of Ceftazidime-Avibactam in Healthy Chinese Subjects[J].Clin Drug Investig.2016,36(2):119-26
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21.Helio S.Sader,Mariana Castanheira,Mariana Castanheira Tigecycline activity tested against carbapenem-resistant Enterobacteriaceae from 18 European nations:results from the SENTRY surveillance program(2010-2013)2015,83(2)::183-186
22.Rafailidis PI,Falagas ME.Options for treating carbapenem-resistant Enterobacteriaceae.Curr Opin Infect Dis.2014 Dec;27(6):479-83.
23.史煜波,胡丽庆,翁幸鐾,等磷霉素、米诺环素等抗生素对bla KPC-2肺炎克雷伯杆菌的体外药敏研究[J].2015,27(5):574
24.Zasowski E J.Theβ-Lactams Strike Back:Ceftazidime-Avibactam[J].Pharmacotherapy.2015,35(8):755-70
25.Hirsh E B,Tan V H.Detection and treatment options for K.pneumoniae Carbapenemases(KPCS):anemerging cause of multidrug-resistant infection[J].J Antimicrob Chemother,2010,65(6):11 19-1125.
26.Rao GG,Ly NS,Haas CE,et al.New dosing strategies for an old antibiotic:pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease[J].Antimicrobial agents and chemotherapy,2014,58(3):1381-1388.
27.Livermore DM,Mushtaq S.Activity of biapenem(RPX2003)combined with the boronateβ-lactamase inhibitor RPX7009 against carbapenem-resistant Enterobacteriaceae[J].J Antimicrob Chemother.2013,68(8):1825-1831
2.MacKenzie F M,Forbes K J,Dorai-John T,et al.Emergenceof a carbapenem-resistant Klebsiella pneumonian[J].Lancet Infect Dis,1997,350(9080):783-785
3.Pfaller M A,Jones RN,Doern GV,et al.Bacterial pathogens isolated from patients with bloodstream infection:frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program(United States and Canada,1997)[J].Antimicrob Agents Chemother,1998,42(7):1762-1770
4.Hoban D J,Biedenbach DJ,Mutnick AH,et al.Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America:results of the SENTRY Antimicrobial Surveillance Study(2000)[J].Diagn Microbiol Infect Dis,2003,45(4):279-285
5.Vital signs:carbapenem-resistant Enterobacteriaceae[R].Centers for Disease Control and Prevention.2013,62(9):165-170
6.Centers for Disease Control and Prevention,2013 http://www.cdc.gov/drugresistance/threat-report-2013
7.胡付品,朱德妹,汪复,等.2013年中国CHINET细菌耐药性监测[J].中国感染与化疗杂志,2014,14(5):365
8.2015年全国细菌耐药监测报告http://www.carss.cn/Download/Details/282
9.Cai JC,Zhou H,Zhang R,et al.Emergence of Serratia marcescens,Klebsiellapneumoniae,and Escherichia coli Isolates possessing the plasmid—mediated carbapenem—hydrolyzing beta-lactamase KPC-2 in intensive care units of a Chinese hospital[J].Antimicrob Agents Chemother,2008,52(6):2014—2018
10.Schwaber MJ,Carmeli Y.Carbapenem-resistant Enterobacteriaceae:a potential threat[J].JAMA,2008,300(24):2911-2913.
11.ZubairAQ,David LP,Brian AP,etal.Treatment Outcome of Bacteremia Due to KPC—Producing Klebsiella pneumoniae:Superiority of Combination Antimicrobial Regimens[J].Antimicrobial Agents and Chemotherapy,2012,56(4):2108-2113.
12.Grace C,David S.Treatment of Klebsiellapneumoniae Carbapenemase(KPC)infections:a review of published case series and case reports[J].Lee and BurgessAnnals of Clinical Microbiology and Antimicrobials,2012,64(3):253
13.朱亚萍,刘荣玉.肺炎克雷伯杆菌耐碳青霉烯类的机制及其防治[J].国际呼吸杂志2011,31(2):125-128.
14.桑福德,抗微生物治疗指南(新译第43版)[M],北京:中国协和医科大学出版社,2014
15.The Johns Hopkins Hospital Antimicrobial Stewardship Program.JHH Antibiotic Management Guidelines(2013-2014)[M].2013,http://www.hopkinsmedicine.org/amp/guidelines/Antibiotic_guidelines.pdf
16.National Committee for Clinical Laboratory Standards(NCCLS).Performance standards for antimicrobial susceptibility testing[J].Information Supplement,M100(S23(2015)).
17.Shujuan Ji,Fangfang Lv,Xiaoxing Du,et al.Cefepime combined with amoxicillin/clavulanic acid:a new choice for the KPC-producing K.pneumoniae infection[J].2015,38(10):108-114
18.Garonzik SM,Li J,Thamlikitkul V,et al.Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients[J].Antimicrobial agents and chemotherapy,2011,55(7):3284-3294.
19.Li J,Learoyd M,Qiu F,et al A Randomized,Phase I Study to Assess the Safety,Tolerability and Pharmacokinetics of Ceftazidime-Avibactam in Healthy Chinese Subjects[J].Clin Drug Investig.2016,36(2):119-26
20.Dong J,Chen YC,Xiong W,et al.Efficacy and safety of biapenem against lower respiratory ractinfectionin elderly Chinese patients and optimaldosing regimen based on pharmacokmetic/pharmacodynamic analysis.J Chemother.2015,2:78.
21.Helio S.Sader,Mariana Castanheira,Mariana Castanheira Tigecycline activity tested against carbapenem-resistant Enterobacteriaceae from 18 European nations:results from the SENTRY surveillance program(2010-2013)2015,83(2)::183-186
22.Rafailidis PI,Falagas ME.Options for treating carbapenem-resistant Enterobacteriaceae.Curr Opin Infect Dis.2014 Dec;27(6):479-83.
23.史煜波,胡丽庆,翁幸鐾,等磷霉素、米诺环素等抗生素对bla KPC-2肺炎克雷伯杆菌的体外药敏研究[J].2015,27(5):574
24.Zasowski E J.Theβ-Lactams Strike Back:Ceftazidime-Avibactam[J].Pharmacotherapy.2015,35(8):755-70
25.Hirsh E B,Tan V H.Detection and treatment options for K.pneumoniae Carbapenemases(KPCS):anemerging cause of multidrug-resistant infection[J].J Antimicrob Chemother,2010,65(6):11 19-1125.
26.Rao GG,Ly NS,Haas CE,et al.New dosing strategies for an old antibiotic:pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease[J].Antimicrobial agents and chemotherapy,2014,58(3):1381-1388.
27.Livermore DM,Mushtaq S.Activity of biapenem(RPX2003)combined with the boronateβ-lactamase inhibitor RPX7009 against carbapenem-resistant Enterobacteriaceae[J].J Antimicrob Chemother.2013,68(8):1825-1831