摘要
目的评价18组抗菌药物组合对临床分离的多重耐药鲍曼不动杆菌(MDRAB)的体外抗菌效应。方法收集2009年10月-2010年5月首都医科大学附属北京友谊医院临床检验中心细菌室分离的非重复鲍曼不动杆菌,肉汤微量稀释法测定抗菌药物单药MIC,棋盘肉汤微量稀释法测定联合用药的部分抑菌浓度(FIC)值。根据FIC值判别药物组合的作用类型。对实验菌株,同一药物组合表现矛盾作用的,用PCR扩增其外排泵基因。结果体外联合作用中利福平+多黏菌素B、亚胺培南+庆大霉素、头孢吡肟+左氧氟沙星协同作用比例大,分别达到68.1%、45.5%、40.9%,米诺环素+利福平、氨苄西林/舒巴坦+妥布霉素、头孢他啶+环丙沙星具有较高的相加作用,分别为81.8%、68.2%、68.2%。有些组合对实验菌株出现协同和拮抗的矛盾作用。选择协同作用的No.19和拮抗作用的No.21、No.26进行耐药基因扩增,基因型表现不同,其中N0.19扩增adeS(一),No.21和No.26扩增adeS(+)。结论18种药物组合里利福平+多黏菌素B存在较高的协同作用,在严重MDRAB感染情况下可以考虑应用该组合。亚胺培南+庆大霉素、头孢吡肟+左氧氟沙星也具有较高的体外协同作用,但是在部分菌株的试验中存在拮抗作用,可能是由于菌株存在adeS基因,某些抗菌药物的应用会激活adeS,使外排泵表达或者过量表达,反而使进人细菌细胞内的药物被泵出,表现为拮抗作用。应用这两类组合时要考虑菌株的个体差异。
Objective To evaluate the activities of 18 pairs of antimicrobials combinations against non - duplicate clinical isolates of multidrug resistant Acinetobacter baumanrrii (MDRAB) in vitro . Methods Collect isolates of Acinetobacter baumannii from different patients from October 2009 to May 2010, which were isolated in Clinical Laboratory Center of Beijing Friendship Hospital, Capital Medical University. Use broth microdilution method to detect MIC of mono-antimicrobial, and checkerboard broth microdilution method to detect combinatied MIC, and calculate fractional inhibitory concentration (FIC) index to determine drug combinations effects. When the performance of the same drug combinations conflicted, appropriate strains were selected for screening of drug-resistant mechanisms by polymerase chain reaction(PCR) , including effiux pump genes. Results In tests in vitro, rifampicin and polymyxin B, imipenem and gentamicin, cefepime and levofloxacin showed synergy at high proportion, 68.1% , 45.5% , 40.9% , respectively. Minocycline and rifampicin, ampicillin/sulbactam and tobramycin. Ceftazidime and ciprofloxacin showed additive effect at high proportion, 81.8% , 68.2% , 68.2% , respectively. There were several combinations which appeared the opposite effects to tested strains. Strains No. 19 corresponding reaction was synergy and No. 21, No. 26 corresponding reactions were antagonism. The three strains above were selected for screening resistant mechanisms. The difference is that genotypes of adeS were negative in No. 19 and positive in No. 21 and No. 26. Conclusion Rifampicin and polymyxin B combination showed synergy against the MDRAB in vitro, which can be considered as the treatment choice for critical infections caused by MDRAB. Imipenem and gentamicin, cefepime and levofloxacin also showed synergy in vitro, but in some isolates showed antagonism. This phenomenon may be due to the gene adeS activated by certain antibiotics, and the activated adeSdrived efflux pump express or overexpress, which made the drugs in bacterial ceils pumped out,causing antagonistic effect. The individual differences in strains should be considered when clinic strain apply these two combinations above.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2011年第10期898-902,共5页
Chinese Journal of Microbiology and Immunology
基金
首都医学发展科研基金(2009-1031)
关键词
多重耐药鲍曼不动杆菌
联合用药
Multi-drug resistant Acinetobacter baumannii
Antimicrobial combination