耐碳青霉烯鲍曼不动杆菌的临床分布及基因组流行病学分析

Analysis on the clinical distribution and genomic epidemiological characteristics of carbapenem-resistant Acinetobacter baumannii

摘要:

[背景] 鲍曼不动杆菌是造成临床感染的重要病原菌之一，其对碳青霉烯类抗生素的耐药形势日益严重，利用基因组测序技术解析其临床分布特征和流行病学规律有助于临床感染的有效防治。[目的] 研究沧州市中心医院2018年检出的200株耐碳青霉烯鲍曼不动杆菌（carbapenem-resistant Acinetobacter baumannii，CRAB）的临床分布和基因组流行病学特征，以期为预防院内感染及抗感染治疗提供理论依据。[方法] 选取2018年各临床科室的耐碳青霉烯鲍曼不动杆菌，采用细菌鉴定及药敏分析仪对16种抗生素进行药敏试验；PCR扩增检测碳青霉烯酶基因；多位点序列分型技术（multilocus sequence typing，MLST）检测菌株序列型；基因组流行病学分析揭示菌株传播关系。[结果] 本院CRAB主要分布在急诊重症加强护理病房（intensive care unit，ICU） （47.0%）、呼吸内科（19.5%）和重症医学科（12.0%），它们对亚胺培南、美罗培南、氨苄西林/舒巴坦、环丙沙星、庆大霉素、左旋氧氟沙星、哌拉西林/他唑巴坦、替卡西林/棒酸、阿米卡星及第三四代头孢类抗生素头孢他定、头孢曲松、头孢吡肟等12种抗生素高度耐药，对复方新诺明呈现出中度耐药趋势，仅对多粘菌素B、美满霉素及头孢哌酮/舒巴坦等3种抗生素敏感。耐药基因聚合酶链式反应（polymerase chain reaction，PCR）结果显示，CRAB菌株中180株（90.0%）携带苯唑西林酶（oxacillinase，OXA）-23基因，19株（9.5%）携带OXA-24基因，只有1株携带OXA-58基因。MLST结果显示，除一株OXA-58阳性株为一个新ST型STnew外，其余均为国际克隆群CC2型。基因组流行病学显示本院菌株共可划分为A、B、C、D这4个类群，以D类群为主要流行群且不同病区均有分布。[结论] 本院CRAB菌株多重耐药严峻，以携带OXA-23基因的CC2克隆群菌株为主，可能存在不同病区间的感染传播，应加强重点科室环境的清洁工作，严格规范医务人员的技术操作规程，慎用碳青霉烯类药物，尽量减少感染并防止耐药率进一步升高。

Abstract:

[Background] Acinetobacter baumannii is one of the most important pathogens causing clinical infection. Its resistance level to carbapenem antibiotics is inceasing year by year. Using genome sequencing technology to analyze the distribution and epidemiological characteristics of A. baumannii can promote the effective prevention and treatment of clinical infection.[Objective] To study the clinical distribution and genomic epidemiological characteristics of 200 carbapenem-resistant Acinetobacter baumannii (CRAB) strains detected in Cangzhou Central Hospital in 2018, aiming to provide a theoretical basis for the prevention of nosocomial infections and anti-infective treatment. [Methods] The susceptibility of 200 CRAB strains isolated from different clinical department to 16 antimicrobial agents was detected by bacterial identification and drug sensitivity analyzer; PCR amplification was used to detect the carbapenemase gene; multi-locus sequence typing (MLST) was performed to detect strains' sequence type; genomic epidemiological analysis revealed transmission relationships among strains from different department. [Results] CRAB strains was mainly distributed in emergency ICU (47.0%), respiratory department (19.5%) and critical medicine department (12.0%). The CRAB strains showed high resistant level to imipenem, meropenem, ampicillin/sulbactam, ticacillin/clavulanic acid, gentamicin, piperacillin/tazobactam, levofloxacin, ciprofloxacin, amikacin and the third and fourth generation cephalosporins (cephalosporin, ceftriaxone and cefepime) and moderate resistance to sulfamethoxazole. Most strains were still sensitive to polymyxin B, minocycline and cefoperazone/sulbactam. The PCR results of antibiotic resistance genes showed that 180 strains (90.0%) of CRAB strains carried OXA-23 gene, 19 strains (9.5%) carried OXA-24 gene, and only 1 strain carried OXA-58 gene. The results of MLST showed that except for the OXA-58 positive strain, the others were all belonged to international clonal group CC2. Genomic epidemiology analysis showed that the strains in this hospital could be divided into four groups A, B, C and D. Group D was the main epidemic group, and it was distributed in different disease areas. [Conclusions] The multidrug resistance of CRAB strain in our hospital is severe, mainly were CC2 strains carrying OXA-23 gene, and there may be infection transmission among different ward areas. The environmental cleaning work of key departments should be strengthened, the technical operation rules of medical staff should be strictly standardized, and carbapenem antibiotics should be used cautiously to reduce infection and prevent further increase of drug resistance rate.