蚌埠地区鲍曼不动杆菌医院感染流行病学调查及耐β-内酰胺类药物机制研究
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摘要
目的:了解鲍曼不动杆菌医院感染现状,研究鲍曼不动杆菌产β-内酰胺酶的特性,分析耐亚胺培南菌株的碳青霉烯酶基因型、同源性,为医院感染的预防、控制以及治疗提供实验室依据。方法:对鲍曼不动杆菌引发的医院感染98例患者的感染情况进行回顾性调查,并用WHONET5.4软件进行药敏分析,明确其感染现状、耐药情况。用头孢硝噻吩(Nitrocefin)纸片显色法筛查鲍曼不动杆菌产β-内酰胺酶的情况,再用三维试验和双纸片协同实验进行AmpC酶、超广谱β-内酰胺酶(ESBLs)及金属β-内酰胺酶(MBLs)的检测。聚合酶链反应(PCR)技术检测耐亚胺培南菌株的碳青霉烯酶基因型。用脉冲场电泳技术(PFGE)对耐亚胺培南的鲍曼不动杆菌分型,聚类分析显示亲缘关系。结果:鲍曼不动杆菌医院感染率较高,其中以ICU病房、骨科、脑外科最常见,分别占感染数的62.24%、12.24%、6.12%;感染部位以呼吸道和手术切口为主,分别占70.41%和18.37%。药敏结果显示亚胺培南耐药率为:64.29%,其它抗生素的耐药率均在65%-90%。98株鲍曼不动杆菌共检出β-内酰胺酶阳性94株,阳性率为95.92%;AmpC酶阳性58株,阳性率为59.18%;ESBLs阳性9株,阳性率为9.18%;未检测出MBL。PCR分析结果显示亚胺培南耐药菌株碳青霉烯酶基因型:blaOXA-23基因型24株、blaOXA-58基因型3株、blaOXA-64-like基因型48株, blaOXA-20、blaOXA-24、blaOXA-48、blaOXA-50、blaOXA-55、blaOXA-60基因型检测结果均为阴性,未检测到金属酶IMP、VIM基因。PFGE结果显示:63株耐亚胺培南的鲍曼不动杆菌通过PFGE分为A,B,C,D,E五型,来自蚌埠医学院第一附属医院的46株菌株分为A、B、C三个基因型,A型为主41株,其中A1亚型有32株,A2亚型8株,A3亚型1株,B型3株,C型2株。蚌埠市中心医院17株中4株和蚌埠医学院第一附属医院A1条带一致,其余:11株为D型包括D1亚型9株,D2亚型2株,2株为E型。结论:本地区鲍曼不动杆菌医院感染率较高,并呈现多重耐药。其产β-内酰胺酶情况严重,是耐β-内酰胺类抗生素的主要原因。对碳青酶烯类的抗生素的主要耐药机制:产OXA-23、OXA-51型碳青霉烯酶。PFGE技术分型结果显示本地区病房、科室及医院之间存在交叉感染现象。
Objective: To survey on the epidemiology, the drug-resistance and producing ofβ-lactamses of Acinetobacter baummanii in nosocomial infections and study on the resistant mechanisms and homology of carbapenem-resistant Acinetobacter baummani in order to provide the strategies of control of the prevalence and therapy in nosocomial infections of Acinetobacter baummanii.
Methods: We retrospectively analysed the data of 98 Acinetobacter baumannii isolates from the inpatients of two hospitals in Bengbu. Drug sensitivity analysis was conducted by WHONET 5.4 software to clarify its infection status and the rates of antibiotic resistance. 98 Acinetobacter baummanii strains were screened forβ-lactamases by Nitrocefin. A modified three-dimensional extract test and the double-disc diffusion test were used to detect phenotypically isolates which produced AmpCβ-lactamases, extended-spectrumβ-lactamases and metal-beta-lactamase. Gene fragments encoding carbapenemase including blaOXA, IMP and VIM were detected by PCR, for definite genotypes, their full length genes were further amplifed and sequenced. The homology of the isolates was determined by pulsed field gelel ectrophoresis (PFGE).
Results: The Acinetobacter baummanii infections associated morbidity was high in our district, particularly in ICU wards, orthopedics wards then was neurosurgery wards. Except imipenem was 64.29%, the resistance rates of Acinetobacter baummanii various of antibiotics were 65%-90%. Among 98 strains of Acinetobacter baumanii producing beta-lactamase bacteria accounted for 94(95.92%); producing AmpC enzyme bacteria accounted for 58(59.18%); producing ESBLs bacteria accounted for 9(9.18%).Genetype analysis of the carbapenemase showed that 48 strains blaOXA-64-liuke、24 strains blaOXA23 and 3 strains blaOXA58 were found, whereas other genes were negative in 63 strains of Immpeinem-resistant Acinetobacter baumanii. Forty-six strains isolated from the first affiliated hospital of Bengbu medical college were classified into type A, B and C based on PFGE pattern. Of these, 41 strains of type A were the dominant strains including subtypes A1(32/41),A2(8/41) and A3(1/41), the remaining isolates belonged to two additional types: 3 to type B and 2 to type C. 4 strains out of 17 from Bengbu Central Hospital were consistent with A1 lane from the first affiliated hospital of Bengbu Medical College. The remaining 13 strains belonged to type D and type E: 11 type D strains including subtypes D1(9/11),D2(2/11) and 2 type E strains.
Conclusions: There is a high morbidity of Acinetobacter baummanii nosocomial infections in our district. The resistance toβ-lactam antibiotics is mainly due to highβ-lactamase produced by Acinetobacter baumannii. Production of OXA-51 and OXA-23 carbapenemase in Acinetobacter baumanii is one of the main mechanisms of imipenem-resistance in Bengbu district. Results of PFGE show there are cross infections among wards, departments and hospitals.
Objective: To survey on the epidemiology, the drug-resistance and producing ofβ-lactamses of Acinetobacter baummanii in nosocomial infections and study on the resistant mechanisms and homology of carbapenem-resistant Acinetobacter baummani in order to provide the strategies of control of the prevalence and therapy in nosocomial infections of Acinetobacter baummanii.
Methods: We retrospectively analysed the data of 98 Acinetobacter baumannii isolates from the inpatients of two hospitals in Bengbu. Drug sensitivity analysis was conducted by WHONET 5.4 software to clarify its infection status and the rates of antibiotic resistance. 98 Acinetobacter baummanii strains were screened forβ-lactamases by Nitrocefin. A modified three-dimensional extract test and the double-disc diffusion test were used to detect phenotypically isolates which produced AmpCβ-lactamases, extended-spectrumβ-lactamases and metal-beta-lactamase. Gene fragments encoding carbapenemase including blaOXA, IMP and VIM were detected by PCR, for definite genotypes, their full length genes were further amplifed and sequenced. The homology of the isolates was determined by pulsed field gelel ectrophoresis (PFGE).
Results: The Acinetobacter baummanii infections associated morbidity was high in our district, particularly in ICU wards, orthopedics wards then was neurosurgery wards. Except imipenem was 64.29%, the resistance rates of Acinetobacter baummanii various of antibiotics were 65%-90%. Among 98 strains of Acinetobacter baumanii producing beta-lactamase bacteria accounted for 94(95.92%); producing AmpC enzyme bacteria accounted for 58(59.18%); producing ESBLs bacteria accounted for 9(9.18%).Genetype analysis of the carbapenemase showed that 48 strains blaOXA-64-liuke、24 strains blaOXA23 and 3 strains blaOXA58 were found, whereas other genes were negative in 63 strains of Immpeinem-resistant Acinetobacter baumanii. Forty-six strains isolated from the first affiliated hospital of Bengbu medical college were classified into type A, B and C based on PFGE pattern. Of these, 41 strains of type A were the dominant strains including subtypes A1(32/41),A2(8/41) and A3(1/41), the remaining isolates belonged to two additional types: 3 to type B and 2 to type C. 4 strains out of 17 from Bengbu Central Hospital were consistent with A1 lane from the first affiliated hospital of Bengbu Medical College. The remaining 13 strains belonged to type D and type E: 11 type D strains including subtypes D1(9/11),D2(2/11) and 2 type E strains.
Conclusions: There is a high morbidity of Acinetobacter baummanii nosocomial infections in our district. The resistance toβ-lactam antibiotics is mainly due to highβ-lactamase produced by Acinetobacter baumannii. Production of OXA-51 and OXA-23 carbapenemase in Acinetobacter baumanii is one of the main mechanisms of imipenem-resistance in Bengbu district. Results of PFGE show there are cross infections among wards, departments and hospitals.
引文
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