Alcántar-Curiel María Dolores, García-Torres Luis Francisco, González-Chávez María Inés, Morfín-Otero Rayo, Gayosso-Vázquez Catalina, Jarillo-Quijada Ma Dolores, Fernández-Vázquez José Luis, Giono-Cerezo Silvia, Rodríguez-Noriega Eduardo, Santos-Preciado José Ignacio
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México.
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México; Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D.F., México.
Arch Med Res. 2014 Oct;45(7):553-60. doi: 10.1016/j.arcmed.2014.10.006. Epub 2014 Nov 1.
Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico.
A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis.
Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted.
Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico.
鲍曼不动杆菌是一种在全球范围内新出现的病原体,最常与医院感染及多重耐药相关。在本研究中,我们确定了墨西哥瓜达拉哈拉市民医院鲍曼不动杆菌医院分离株对碳青霉烯类耐药的机制及克隆多样性。
对2004年至2011年期间鉴定出的总共303株鲍曼不动杆菌临床分离株,使用多种微生物学和分子方法分析其对碳青霉烯类的耐药性。采用脉冲场凝胶电泳确定这些分离株的克隆相关性。
在303株分离株中,84%对美罗培南耐药,71.3%对亚胺培南耐药,通过表型分析确定,78.3%的耐药分离株金属β-内酰胺酶呈阳性。此外,49.6%的碳青霉烯类中介或耐药分离株携带blaOXA - 72基因,1.2%携带blaVIM - 1基因。在存在外排泵抑制剂羰基氰3 - 氯苯腙的情况下,外排泵表型分别导致14.5%的耐药分离株对美罗培南敏感性降低,31.6%的耐药分离株对亚胺培南敏感性降低。代表不同碳青霉烯类耐药模式的菌株表现出22 kDa、29 kDa、33 kDa和43 kDa外膜蛋白(OMPs)表达降低。在所研究的细菌群体中,鉴定出48个不同的克隆,其中两个为主导克隆且持续传播。
碳青霉烯酶的产生与外排泵表达、OMPs表达降低以及克隆的交叉传播似乎是鲍曼不动杆菌中观察到的碳青霉烯类耐药高频率的主要原因。据我们所知,这是第一项确定墨西哥鲍曼不动杆菌中与碳青霉烯类耐药相关分子机制的研究。