AP-HP, Hôpital Louis Mourier, Service de Microbiologie-Hygiène, Colombes, France.
Clin Microbiol Infect. 2011 Apr;17(4):557-65. doi: 10.1111/j.1469-0691.2010.03298.x.
Escherichia coli is one of the major pathogens responsible for bactaeremia. Empirical antibiotherapy of these infections usually relies on third-generation cephalosporins (3GCs). Thus, the occurrence and epidemiology of 3GC-resistant strains have to be monitored. The French prospective multicentre study COLIBAFI collected 1081 strains of E. coli responsible for bacteraemia in 2005. In the present work, the prevalence of resistance to 3GCs was evaluated, and the implicated molecular mechanisms were characterized by specific PCR and sequencing. Phylogenetic grouping, O-typing, pulsed-field gel electrophoresis and virulence factor analysis were used to investigate the genetic background of the 3GC-resistant (3GC-R) strains. Clinical features of the patients with documented data (n = 1051) were analysed. Decreased susceptibility to 3GCs was observed in 41 strains (3.8%): 19, 18 and four had extended-spectrum β-lactamase (ESBL), AmpC cephalosporinase and OXA-type penicillinase phenotypes, respectively. Pulsed-field gel electrophoresis revealed that the 3GC-R strains constitute a diverse population. All but one of the strains with an ESBL phenotype produced a CTX-M-type enzyme, and six of them belonged to the widespread intercontinental clone O25b:H4-ST131. AmpC phenotype strains harboured various chromosomal ampC promoter and coding region mutations and/or the bla(CMY-2) plasmidic gene. 3GC-R strains carried fewer virulence factors and were more co-resistant to other antibiotics than 3GC-susceptible (3GC-S) strains. Infections with 3GC-R strains were mostly community-acquired and, as compared with those caused by their 3GC-S counterparts, were more severe. Underlying chronic disease and prior use of antibiotics were independent risk factors for development of a 3GC-R strain bacteraemia. The fact that the molecular support of 3GC resistance is mainly plasmid-mediated represents a potentially epidemic threat.
大肠埃希菌是引起菌血症的主要病原体之一。这些感染的经验性抗生素治疗通常依赖于第三代头孢菌素（3GCs）。因此，必须监测 3GC 耐药菌株的发生和流行病学。法国前瞻性多中心研究 COLIBAFI 于 2005 年收集了 1081 株大肠埃希菌引起的菌血症菌株。在本工作中，评估了对 3GCs 的耐药率，并通过特异性 PCR 和测序来描述相关的分子机制。通过谱系分组、O 型分型、脉冲场凝胶电泳和毒力因子分析，研究了 3GC 耐药（3GC-R）菌株的遗传背景。对有记录数据的患者（n=1051）的临床特征进行了分析。发现 41 株（3.8%）对 3GCs 的敏感性降低：19、18 和 4 株分别表现出广谱β-内酰胺酶（ESBL）、AmpC 头孢菌素酶和 OXA 型青霉素酶表型。脉冲场凝胶电泳显示 3GC-R 菌株构成了一个多样化的群体。具有 ESBL 表型的菌株中，除一株外均产生 CTX-M 型酶，其中 6 株属于广泛传播的洲际克隆 O25b:H4-ST131。AmpC 表型菌株携带各种染色体 ampC 启动子和编码区突变和/或 bla(CMY-2)质粒基因。3GC-R 菌株携带的毒力因子较少，对其他抗生素的协同耐药性也高于 3GC-S 菌株。3GC-R 菌株引起的感染大多为社区获得性，与 3GC-S 菌株引起的感染相比，更为严重。基础慢性疾病和抗生素的使用是发展为 3GC-R 菌株菌血症的独立危险因素。3GC 耐药的分子支持主要是质粒介导的，这代表了一种潜在的流行威胁。
