5年间鲍曼不动杆菌产碳青霉烯酶特性与耐药相关性研究

Characterization of carbapenemases and its dependability in drug resistance of Acinetobacter baumannii： a 5-year analysis

目的研究2002-2006年每年3-5月临床分离鲍曼不动杆菌中碳青霉烯酶的分布与变迁情况及其与碳青霉烯类抗生素耐药的相关性。方法琼脂稀释法检测亚胺培南（IPM）和美罗培南（MEN）对174株鲍曼不动杆菌的最低抑菌浓度（MIC）；2-巯基丙酸（2-MPA）和乙二胺四乙酸（EDTA）协同试验进行金属β-内酰胺酶表型检测；PCR扩增金属β-内酰胺酶（MBL）VIM、IMP和苯唑西林酶OXA-23、OXA-24、OXA-51、OXA-58相关基因。结果2002-2006年每年3-5月临床分离的鲍曼不动杆菌对IPM的耐药率分别为0（0／20）、2．6％（1／38）、0（0／36）、34．9％（15／43）和59．5％（22／37），对MEN的耐药率分别为0（0／20）、5．3％（2／38）、0（0／36）、20．9％（9／43）和51．4％（19／37）；15．5％（27／174）的菌株OXA-23阳性，72．4％（126／174）的菌株OXA-51阳性，其中15．5％（27／174）菌株同时产OXA-51和OXA-23酶，OXA-23的阳性率从2002年的0上升到2006年的48．6％，OXA-51的阳性率从2002年的35．0％上升到2006年的89．2％；所有菌株均未检出OXA-24、OXA-58、IMP及VIM基因。结论5年间鲍曼不动杆菌中OXA-23、OXA-51的检出率及其对碳青霉烯类抗生素的耐药性均呈上升趋势；产OXA-23型β-内酰胺酶是本组鲍曼不动杆菌对碳青霉烯类抗生素产生耐药的重要原因，OXA-51可能与鲍曼不动杆菌对碳青霉烯类抗生素的低水平耐药有关。

Objective To study the distribution and diversity of carbapenemases in Acinetobacter baumannii and its depen-dability in drug resistance from March until May annually between 2002-2006. Methods The minimum inhibitory concentration （MIC） values for meropenem （MEN） and imipenem （IPM） against 174 A. baumannii were determined with an agar dilution method. Phenotypic detection of metallo-β-1actamase was performed by 2-MPA （ mercaptopropionic acid） and EDTA （ ethylenediaminetet-raacetic acid） inhibitor synergy test. Metallo-β-1actamase （VIM, IMP） genes and oxacillin-β-1actamase （OXA-23, OXA-24, OXA-51, OXA-58） genes were determined by PCR. Results IPM resistance in A. baumannii from 2002 to 2006 were 0（0/20）, 2.6% （ 1/38）, 0（0/36）, 34.9% （ 15/43 ） and 59.5% （22/37）, respectively, MEN resistance were 0（0/20） , 5.3% （2/38）, 0（0/36） , 20.9% （9/43） and 51.4% （19/37）, respectively. OXA-23 gene was amplified from 15.5% （27/174） isolates, and OXA-51 from 72.4% （126/174）. There were 15.5% （27/174） isolates producing OXA-51 and OXA-23 simultaneously. OXA-23 positive strains increased from 0 in 2002 to 48.6% in 2006 and OXA-51 positive strains increased from 35.0% in 2002 to 89.2% in 2006. All 174 isolates were negative by PCR for genes OXA-24, OXA-58, IMP and VIM. Conclusion The incidence of OXA-23, OXA-51 and the resistance of carbapenems in A. baumannii were increasing in the 5 years. OXA-23 production is the important mechanism of carbapenems resistance. There may be dependability between OXA-51 and low-level carbapenems resistance in A. baumannii.