目的 观察并探讨分离自烧伤患者的碳青霉烯类抗生素耐药鲍氏不动杆菌(CRAB)的耐药机制及体外联合用药的抗菌活性. 方法 2011年1月-2013年7月,收集从笔者单位收治的烧伤患者创面分泌物、痰液及静脉导管表面附着物中分离鉴定的非重复鲍氏不动杆菌135株,采用K-B纸片扩散法测定鲍氏不动杆菌对12种临床常用抗生素的耐药性.针对CRAB菌株,行纸片协同试验筛选产金属β内酰胺酶(MBL)菌株,结合前述结果对比产MBL与不产MBL菌株耐药率.通过微量肉汤稀释法测定头孢哌酮/舒巴坦、亚胺培南、头孢吡肟、氨苄西林/舒巴坦和阿米卡星单用对产MBL的CRAB的MIC、对50％菌株的MIC(MIC50)、对90％菌株的MIC(MIC90).采用琼脂稀释的棋盘格法测定阿米卡星分别与头孢哌酮/舒巴坦、亚胺培南、头孢吡肟、氨苄西林/舒巴坦联用对产MBL的CRAB的MIC、MIC50、MIC90,计算联用药物的部分抑菌浓度(FIC)指数以判断抗菌效应,其中FIC小于或等于0.5为协同,大于0.5且小于或等于1.0为相加,大于1.0且小于或等于2.0为无关,大于2.0为拮抗,将协同及相加视为有效,将无关与拮抗视为无效,计算有效率.对部分数据行x2检验. 结果 135株鲍氏不动杆菌对亚胺培南、美罗培南、头孢他啶等耐药率较高,对哌拉西林/他唑巴坦、氨苄西林/舒巴坦耐药率较低.共筛选出120株CRAB占88.89％,其中94株产MBL占78.33％.产MBL的CRAB对哌拉西林/他唑巴坦、亚胺培南、美罗培南、哌拉西林和头孢吡肟的耐药率分别为59.5％、87.2％、93.5％、87.0％、86.0％,显著高于不产MBL的CRAB的43.0％、81.3％、87.5％、78.4％、64.0％(x2值为4.571 ～8.260,P＜0.05或P＜0.01).5种抗菌药物单用时对产MBL的CRAB的抑菌浓度中,氨苄西林/舒巴坦的MIC、MIC50、MIC90最低,分别为4.00、16、64μg/mL;头孢吡肟的MIC、MIC50、MIC90较高,分别为32.00、128、512 μg/mL.阿米卡星与4种药物联用时各种药物的MIC、MIC50、MIC90较单用时降低50.00％～98.44％.阿米卡星分别与氨苄西林/舒巴坦、头孢哌酮/舒巴坦、头孢吡肟、亚胺培南联用抗菌效果中协同、相加、无关、拮抗作用菌株数分别为40、33、6、15株,42、30、5、17株,38、15、19、22株,34、2、37、21株;抗菌有效率依次降低,分别为77.7％、76.6％、56.4％、38.3％,其中前两者分别显著高于后两者(x2值为8.618～29.889,P值均小于0.01). 结论 从笔者单位近3年收治烧伤患者标本中分离的CRAB,对碳青霉烯类抗生素的耐药机制以产MBL为主,阿米卡星与上述4种药物联用对CRAB的抗菌效果强于5种药物单用,以阿米卡星与含酶抑制剂复合剂联用效果尤为明显.
目的 觀察併探討分離自燒傷患者的碳青黴烯類抗生素耐藥鮑氏不動桿菌(CRAB)的耐藥機製及體外聯閤用藥的抗菌活性. 方法 2011年1月-2013年7月,收集從筆者單位收治的燒傷患者創麵分泌物、痰液及靜脈導管錶麵附著物中分離鑒定的非重複鮑氏不動桿菌135株,採用K-B紙片擴散法測定鮑氏不動桿菌對12種臨床常用抗生素的耐藥性.針對CRAB菌株,行紙片協同試驗篩選產金屬β內酰胺酶(MBL)菌株,結閤前述結果對比產MBL與不產MBL菌株耐藥率.通過微量肉湯稀釋法測定頭孢哌酮/舒巴坦、亞胺培南、頭孢吡肟、氨芐西林/舒巴坦和阿米卡星單用對產MBL的CRAB的MIC、對50％菌株的MIC(MIC50)、對90％菌株的MIC(MIC90).採用瓊脂稀釋的棋盤格法測定阿米卡星分彆與頭孢哌酮/舒巴坦、亞胺培南、頭孢吡肟、氨芐西林/舒巴坦聯用對產MBL的CRAB的MIC、MIC50、MIC90,計算聯用藥物的部分抑菌濃度(FIC)指數以判斷抗菌效應,其中FIC小于或等于0.5為協同,大于0.5且小于或等于1.0為相加,大于1.0且小于或等于2.0為無關,大于2.0為拮抗,將協同及相加視為有效,將無關與拮抗視為無效,計算有效率.對部分數據行x2檢驗. 結果 135株鮑氏不動桿菌對亞胺培南、美囉培南、頭孢他啶等耐藥率較高,對哌拉西林/他唑巴坦、氨芐西林/舒巴坦耐藥率較低.共篩選齣120株CRAB佔88.89％,其中94株產MBL佔78.33％.產MBL的CRAB對哌拉西林/他唑巴坦、亞胺培南、美囉培南、哌拉西林和頭孢吡肟的耐藥率分彆為59.5％、87.2％、93.5％、87.0％、86.0％,顯著高于不產MBL的CRAB的43.0％、81.3％、87.5％、78.4％、64.0％(x2值為4.571 ～8.260,P＜0.05或P＜0.01).5種抗菌藥物單用時對產MBL的CRAB的抑菌濃度中,氨芐西林/舒巴坦的MIC、MIC50、MIC90最低,分彆為4.00、16、64μg/mL;頭孢吡肟的MIC、MIC50、MIC90較高,分彆為32.00、128、512 μg/mL.阿米卡星與4種藥物聯用時各種藥物的MIC、MIC50、MIC90較單用時降低50.00％～98.44％.阿米卡星分彆與氨芐西林/舒巴坦、頭孢哌酮/舒巴坦、頭孢吡肟、亞胺培南聯用抗菌效果中協同、相加、無關、拮抗作用菌株數分彆為40、33、6、15株,42、30、5、17株,38、15、19、22株,34、2、37、21株;抗菌有效率依次降低,分彆為77.7％、76.6％、56.4％、38.3％,其中前兩者分彆顯著高于後兩者(x2值為8.618～29.889,P值均小于0.01). 結論 從筆者單位近3年收治燒傷患者標本中分離的CRAB,對碳青黴烯類抗生素的耐藥機製以產MBL為主,阿米卡星與上述4種藥物聯用對CRAB的抗菌效果彊于5種藥物單用,以阿米卡星與含酶抑製劑複閤劑聯用效果尤為明顯.
목적 관찰병탐토분리자소상환자적탄청매희류항생소내약포씨불동간균(CRAB)적내약궤제급체외연합용약적항균활성. 방법 2011년1월-2013년7월,수집종필자단위수치적소상환자창면분비물、담액급정맥도관표면부착물중분리감정적비중복포씨불동간균135주,채용K-B지편확산법측정포씨불동간균대12충림상상용항생소적내약성.침대CRAB균주,행지편협동시험사선산금속β내선알매(MBL)균주,결합전술결과대비산MBL여불산MBL균주내약솔.통과미량육탕희석법측정두포고동/서파탄、아알배남、두포필우、안변서림/서파탄화아미잡성단용대산MBL적CRAB적MIC、대50％균주적MIC(MIC50)、대90％균주적MIC(MIC90).채용경지희석적기반격법측정아미잡성분별여두포고동/서파탄、아알배남、두포필우、안변서림/서파탄련용대산MBL적CRAB적MIC、MIC50、MIC90,계산련용약물적부분억균농도(FIC)지수이판단항균효응,기중FIC소우혹등우0.5위협동,대우0.5차소우혹등우1.0위상가,대우1.0차소우혹등우2.0위무관,대우2.0위길항,장협동급상가시위유효,장무관여길항시위무효,계산유효솔.대부분수거행x2검험. 결과 135주포씨불동간균대아알배남、미라배남、두포타정등내약솔교고,대고랍서림/타서파탄、안변서림/서파탄내약솔교저.공사선출120주CRAB점88.89％,기중94주산MBL점78.33％.산MBL적CRAB대고랍서림/타서파탄、아알배남、미라배남、고랍서림화두포필우적내약솔분별위59.5％、87.2％、93.5％、87.0％、86.0％,현저고우불산MBL적CRAB적43.0％、81.3％、87.5％、78.4％、64.0％(x2치위4.571 ～8.260,P＜0.05혹P＜0.01).5충항균약물단용시대산MBL적CRAB적억균농도중,안변서림/서파탄적MIC、MIC50、MIC90최저,분별위4.00、16、64μg/mL;두포필우적MIC、MIC50、MIC90교고,분별위32.00、128、512 μg/mL.아미잡성여4충약물련용시각충약물적MIC、MIC50、MIC90교단용시강저50.00％～98.44％.아미잡성분별여안변서림/서파탄、두포고동/서파탄、두포필우、아알배남련용항균효과중협동、상가、무관、길항작용균주수분별위40、33、6、15주,42、30、5、17주,38、15、19、22주,34、2、37、21주;항균유효솔의차강저,분별위77.7％、76.6％、56.4％、38.3％,기중전량자분별현저고우후량자(x2치위8.618～29.889,P치균소우0.01). 결론 종필자단위근3년수치소상환자표본중분리적CRAB,대탄청매희류항생소적내약궤제이산MBL위주,아미잡성여상술4충약물련용대CRAB적항균효과강우5충약물단용,이아미잡성여함매억제제복합제련용효과우위명현.
Objective To investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.Methods A total of 135 strains ofAcinetobacter baumannii (AB) from wound excretion,sputum,and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually.Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method.Among the CRAB strains,double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains,and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared.Minimal inhibitory concentration (MIC),50％ MIC (MIC50),and 90％ MIC (MIC90) of cefoperazone/sulbactam,imipenem,cefepime,ampicillin/sulbactam,and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method.MIC,MIC50,and MIC90 of amikacin respectively combined with imipenem,cefoperazone/sulbactam,cefepime,or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar.Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics.Synergy with FIC lower than or equal to 0.5,or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective,and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective.The effective rate was calculated.Data were processed with Chi-square test.Results The resistant rates of the 135 strains of AB to imipenem,meropenem,and ceftazidime were high,and those of piperacillin/tazobactam and ampicillin/sulbactam were low.A total of 120 strains of CRAB was screened,accounting for 88.89％,among which the MBL-producing strains accounted for 78.33％(94/120).The resistant rates of MBL-producing strains to piperacillin/tazobactam,imipenem,meropenem,piperacillin,and cefepime were respectively 59.5％,87.2％,93.5％,87.0％,86.0％,and they were significantly higher than those of non-MBL-producing strains (respectively 43.0％,81.3％,87.5％,78.4％,64.0％,withx 2 values from 4.571 to 8.260,P ＜ 0.05 or P ＜ 0.01).Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains,MIC,MIC50,and MIC90 of ampicillin/sulbactam were the lowest,respectively 4.00,16,64 μg/mL,while thosc of cefepime were high,respectively 32.00,128,512 μg/mL.MIC,MIC50,and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00％ to 98.44％ as compared with that of single administration of each antibiotic.Among the 94 strains of MBL-producing CRAB,the synergic,additive,indifferent,and antagonistic effects were respectively observed in 40,33,6,and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42,30,5,17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38,15,19,22 strains applied with combination of amikacin and cefepime; 34,2,37,21 strains applied with combination of amikacin and imipenem,among which the antibacterial effective rates decreased successively,respectively 77.7％,76.6％,56.4％,and 38.3％.The former two rates were respectively significantly higher than the latter two rates (withx 2 values from 8.618 to 29.889,P values below 0.01).Conclusions Production of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years.The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly,and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.
