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      CARACTERIZACIÓN MOLECULAR DE β-LACTAMASAS DE ESPECTRO EXTENDIDO EN CEPAS DE ESCHERICHIA COLI CAUSANTES DE INFECCIÓN URINARIA EN PACIENTES IMMUNOCROMPROMETIDOS Translated title: MOLECULAR CHARACTERIZATION OF EXTENDED-SPECTRUM β-LACTAMASES IN STRAINS OF ESCHERICHIA COLI CAUSING URINARY INFECTION IN IMMUNOCOMPROMISED PATIENTS

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          Abstract

          Introducción. La Infección del Tracto Urinario (ITU) es la infección bacteriana que más se diagnostica en el mundo y su agente causal más frecuente es Escherichia coli (E. coli), bacteria que ha adquirido importancia por su capacidad de producir betalactamasa de espectro extendido (BLEE), lo cual dificulta su tratamiento y hace más frecuentes las infecciones recurrentes y recidivantes incluyendo sus complicaciones, sobretodo en pacientes inmunocomprometidos. Objetivo. Identificar pacientes con ITU producidas por E. coli productoras de BLEE y evaluar su espectro antibacteriano y molecular. Material y métodos. Estudio longitudinal y prospectivo realizado con muestras urinarias de 53 pacientes de la Caja Nacional de Salud en La Paz-Bolivia. Se aisló como agente causal a E. coli en el 72% de las muestras, de estas, 35 presentaron fenotipo BLEE sensibles a imipenem, gentamicina y nitrofurantoina (100%) y amikacina (94%). Los ensayos de fenotipificación reportaron predominio del tipo PhP-2 y los filogenéticos (PCR y secuenciación) identificaron predominio de bla CTX-M-15 asociada a bla TEM-1. Conclusión. Los fármacos de primera línea para el tratamiento de la ITU no son adecuados, haciendo a los pacientes más susceptibles a infecciones recurrentes y recidivantes. Se deben identificar precozmente y tratar eficazmente las ITU producidas por cepas de E. coli productoras de BLEE.

          Translated abstract

          Introduction. Urinary tract infection (UTI) is the most common diagnosed bacterial infection in the world and its most frequent causal agent is the Escherichia coli (E. coli), a bacterium that has gained importance due to its ability to produce extended-spectrum beta-lactamase (ESBL), which makes treatment difficult and leads to more frequent recurrent infections including their complications, and even more in immunocompromised patients. Objective. To identify patients with UTI caused by ESBL-producing E. coli and evaluate their antibacterial and molecular spectrum. Material and methods. A longitudinal and prospective study performed with urinary samples from 53 patients of Caja Nacional de Salud in La Paz, Bolivia. In 72% of the samples, E. coli was isolated as a causative agent, of these, 35 had ESBL phenotype, sensitive to imipenem, gentamicin and nitrofurantoin (100%) and amikacin (94%). Phenotyping assays reported a predominance of PhP-2 type and phylogenetic assays (PCR and sequencing) identified a predominance of bla CTX-M-15 associated with bla TEM-1. Conclusion. Early recognition and effective treatment of UTI produced by multiresistant ESBL-producing strains of E. coli should be recognized based on the evidence obtained.

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          Extended-Spectrum β-Lactamases: a Clinical Update

          Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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            Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistant E. coli infections in the United States.

            Escherichia coli sequence type ST131 (O25:H4), associated with the CTX-M-15 extended-spectrum beta-lactamase, has emerged internationally as a multidrug-resistant pathogen but has received little attention in the United States. From the SENTRY and Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance programs, 127 E. coli clinical isolates from hospitalized patients across the United States in 2007, stratified by extended-spectrum cephalosporin and fluoroquinolone phenotype and bla(CTX-M-15) genotype, were assessed for phylogenetic group, ST131 status, susceptibility profile, virulence genotype, gyrA and parC sequence, and pulsed-field gel electrophoresis profile. The 54 identified ST131 isolates (all fluoroquinolone resistant) accounted for an estimated 17% of the source populations, including 67%-69% of isolates resistant to extended-spectrum cephalosporins or fluoroquinolones, 55% of those resistant to both fluoroquinolones and trimethoprim-sulfamethoxazole, and 52% of multidrug-resistant isolates. Their distinctive virulence profiles were more extensive compared with other antimicrobial-resistant isolates but similarly extensive compared with antimicrobial-susceptible isolates. Pulsed-field profiling suggested ongoing dissemination among locales, with concentration of bla(CTX-M-15) within specific ST131 lineages. A historical ST131 isolate lacked the 2007 ST131 isolates' conserved fluoroquinolone resistance-associated single-nucleotide polymorphisms in gyrA and parC. A single E. coli clonal group, ST131, probably caused the most significantly antimicrobial-resistant E. coli infections in the United States in 2007, thereby constituting an important new public health threat. Enhanced virulence and/or antimicrobial resistance compared with other E. coli, plus ongoing dissemination among locales, may underlie ST131's success. Urgent investigation of the sources and transmission pathways of ST131 is needed to inform mitigation efforts.
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              Insights into a Multidrug Resistant Escherichia coli Pathogen of the Globally Disseminated ST131 Lineage: Genome Analysis and Virulence Mechanisms

              Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.
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                Author and article information

                Journal
                rmcmlp
                Revista Médica La Paz
                Rev. Méd. La Paz
                Colegio Médico de La Paz (La Paz, , Bolivia )
                1726-8958
                2019
                : 25
                : 2
                : 10-18
                Affiliations
                [06] La Paz orgnameLaboratorios Ciencia y Medicina Bolivia
                [01] Antofagasta orgnameUniversidad de Antofagasta orgdiv1Departamento de Tecnología Médica Chile romarudo@ 123456yahoo.es
                [02] La Paz orgnameCaja Nacional de Salud orgdiv1Hospital Materno Infantil Bolivia
                Article
                S1726-89582019000200002 S1726-8958(19)02500200002
                140a621f-ee65-4f1f-bd25-6542c9ae4622

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 19 September 2019
                : 12 March 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 55, Pages: 9
                Product

                SciELO Bolivia

                Self URI: Texto completo solamente en formato PDF (ES)
                Categories
                ARTÍCULO ORIGINAL

                Urinary tract infection,ESBL-producing Escherichia coli,Molecular and antibacterial characterization,Infección del tracto urinario,Escherichia coli productora de BLEE,Caracterización molecular y antibacteriana

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