lunes, 21 de enero de 2013

Proyecto FONDECYT Adjudicado por el Dr. Gerardo González en el concurso Regular FONDECYT 2013

Se transcribe el Resumen del Proyecto FONDECYT obtenido por el Dr. Gerardo González Rocha, luego que 9 grupos de investigación de la Facultad de Ciencias Biológicas se adjudicaron proyectos presentados al Concurso de Proyectos Regular Fondecyt  2013.
En este trabajo de investigación participan además: Universidad de Concepción:  Dras.:  Helia Bello Toledo y  Mariana Domínguez Yévenes. Instituto de Salud Pública de Chile: Dres.: Juan Carlos Hormazábal Opazo, Jorge Fernández Órdenes, Pamela Araya Rodríguez y Soledad Prat Miranda.

Título  del  Proyecto
“Microbiological and molecular characterization of carbapenemase-producing Enterobacteriaceae and geneticplatforms of this important and emerging beta-lactamase in Chileanhospitals”.

Soon after the beginning of antibiotic usage, the antimicrobial resistance (AR) has been increasing in many bacterial species, especially during last 10 years. Thus, on April 7th, 2011 the WHO established during the World Health Day celebration the lemma “Antimicrobial resistance: no action today, no cure tomorrow”,introducing a six-point policy package to combat the spread of AR. In general, costs of infections are high-priced, by increaseof length of stay and morbi-mortality. Additional problem is the loss of low-cost and old antibiotics to treat it, considering the limited development of new antibiotics. This situation reveals the importance of improving the infection control actions and developing antimicrobial surveillance programs to allow the detection of: resistant bacteria, emergence and spread of new resistance mechanisms, and identification of the population structure of resistant bacteria, especially the so-called high-risk clones. These actions and knowledge will help to diminish the emergence and dissemination of antibiotic resistant bacteria, mainly inside hospitals. Carbapenems (CBP) are the main antibiotics choice to treat multidrug-resistantenterobacteria, particularly ESBL producers. However, the vast consumption of CBP has led to the emergence of clinical isolates with resistance or reduced susceptibility, mainly among Klebsiella pneumoniae and Escherichia coli. Therefore, the emergence of these strains constitutes a worldwide serious threat, since the therapeutic options are extremely limited, forcing the clinicians to use old and discharged antibiotics, such as colistin, which has a significant toxicity, and also, to which some resistant strains have been reported. The resistance to CBP in enterobacteria is due to several mechanisms: production of CBP-hydrolysingβ-lactamases (carbapenemases, [CBPase]);alteration in porin, and up-regulation of efflux pump system, associated with ESBL or high levels AmpCenzymes production. In Chile,enterobacteria showing resistance or decreased susceptibility to CBP have increased importantly during the last years, and worse yet, the first strain of K. pneumoniae producing KPC CBPase was reported in March2012, and at time of submission this proposal had already informed other 6 cases byInstituto de SaludPública de Chile (ISP). However, this situation could be worse, due to difficulties in the phenotypic detection of these resistant isolates. There are some strains harboringblaKPC gene, but the minimal inhibitory concentration (MIC) of CBP, although elevated, is still within the susceptible category. For this reason, in 2010 CLSI published new breakpointsfor CBP for enterobacteria. According to these the strains will be categorized as susceptible to imipenem and meropenem with MIC ≤1μg/ml and ertapenem with MIC ≤0.5μg/ml, allowing an early detection of CBP-resistant enterobacteria (CBPRE). It is therefore very important to know which enzymes are responsible for CBP resistance in Chilean strains of enterobacterias, which are the genetic platforms whereblagenes are located, how these genes are mobilized among Gram-negative bacteria in hospitals and community, and to know clonalityof clinical CBPase-producer strains. Consequently, the aims of this proposal is to determine the prevalence of CBPaseamongCBPRE isolated in Chilean hospitals, the molecular clonality, and the genetic platforms where the CBPase-encoding genes are located, andtheir dissemination to other susceptible Gram-negative bacilli.The strains included in this study will be those collected by ISP in the National Surveillance Program of CBPRE, and will be evaluated for: 1) antibiotic profiles and levels of resistance following the CLSI guidelines; 2) clonality by analysis of chromosomal DNA restriction patterns by PFGE and MLST; 3) CBPaseproduction by the boronic acid- or oxacillin-based modified Hodge test for class A CBPase, and by imipenem/imipenem+EDTA disk method for metalloβ-lactamases; 4) CBPase-encoding blagenes by PCR and sequencing; 5) localization of blagenes studying plasmid content, plasmid curing, and transference capability by mating experiments, and 6) detection of blagenes coding for CBP resistance as gene cassettes in integrons by PCR and DNA sequencing of the variable regions of these structures. The results of this study will allow knowing the genetic diversity of CBPRE CBPase-producer and the epidemiological relatedness between these isolates. This knowledge will contribute to set up or reinforce epidemiologic control measures improving the control of nosocomial infections in the Chilean hospitals, and also to transfer the experience and knowledge to other professional. On the other hand, understanding the genetic surrounding of the genes encoding this resistance, will allow us to know the feasibility of dissemination of CBPase. Additionally this knowledge is a desirable pre-requisite to the design and development of intervention strategies intended to minimize the threat poses by infections produced by CBPRE.

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