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1.
Lancet HIV ; 10(3): e195-e201, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36610439

RESUMEN

Getting to Zero is a commonly cited strategic aim to reduce mortality due to both HIV and avoidable deaths among people with HIV. However, no clear definitions are attached to these aims with regard to what constitutes HIV-related or preventable mortality, and their ambition is limited. This Position Paper presents consensus recommendations to define preventable HIV-related mortality for a pragmatic approach to public health monitoring by use of national HIV surveillance data. These recommendations were informed by a comprehensive literature review and agreed by 42 international experts, including clinicians, public health professionals, researchers, commissioners, and community representatives. By applying the recommendations to 2019 national HIV surveillance data from the UK, we show that 30% of deaths among people with HIV were HIV-related or possibly HIV-related, and at least 63% of these deaths were preventable or potentially preventable. The application of these recommendations by health authorities will ensure consistent monitoring of HIV elimination targets and allow for the identification of inequalities and areas for intervention.


Asunto(s)
Infecciones por VIH , Humanos , Consenso , Salud Pública , Personal de Salud
2.
J Vet Diagn Invest ; 26(1): 42-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24398904

RESUMEN

Staphylococcus pseudintermedius is a commensal and opportunistic pathogen of dogs. It is mainly implicated in canine pyoderma, as well as other suppurative conditions of dogs. Although bacterial culture is routinely used for clinical diagnosis, molecular methods are required to accurately identify and differentiate S. pseudintermedius from other members of the Staphylococcus intermedius group. These methods, owing largely to their cost, are not easy to implement in nonspecialized laboratories or veterinary practices. In the current study, loop-mediated isothermal amplification (LAMP), a novel isothermal nucleic acid amplification procedure, was employed to develop a rapid, specific, and sensitive S. pseudintermedius assay. Different detection strategies, including the use of a lateral flow device, were evaluated. The assay was evaluated for cross-reactivity against 30 different bacterial species and validated on a panel of 108 S. pseudintermedius isolates, originating from different dog breeds and locations within the United Kingdom. The assay was specific, showing no cross-reactivity during in silico and in vitro testing. When tested using DNA extracts prepared directly from 35 clinical surgical site swabs, the assay could detect S. pseudintermedius in less than 15 min, with a diagnostic sensitivity of 94.6%, superior to that of a polymerase chain reaction method. The LAMP assay also had an analytical sensitivity in the order of 10(1) gene copies, and the amplified products were readily detected using a lateral flow device. The LAMP assay described in the present study is simple and rapid, opening up the possibility of its use as a diagnostic tool within veterinary practices.


Asunto(s)
Enfermedades de los Perros/microbiología , Técnicas de Amplificación de Ácido Nucleico/veterinaria , Infecciones Estafilocócicas/veterinaria , Staphylococcus/aislamiento & purificación , Animales , ADN Bacteriano/química , ADN Bacteriano/genética , Enfermedades de los Perros/diagnóstico , Perros , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/normas , Polimorfismo de Longitud del Fragmento de Restricción , Sensibilidad y Especificidad , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Staphylococcus/genética
3.
J Nurs Educ ; 52(10): 567-73, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24040769

RESUMEN

Multiple challenges must be addressed when educational research is being conducted that involves a teaching innovation at multiple sites over time, including the consistent adoption and use of the intervention, attrition, response rates, and other aspects related to managing a complex study. After an 18-month nursing education study was conducted at multiple institutions across the United States, the authors' study team reflected on strategies that worked well, the challenges faced, and what could have been done differently. This article details the challenges and offers recommendations for other researchers conducting similar studies. Recommendations related to communication and engagement, innovation fidelity, survey fatigue, multiple institutional review board applications, and flexibility are provided.


Asunto(s)
Estudios Multicéntricos como Asunto , Investigación en Educación de Enfermería/organización & administración , Comunicación , Comités de Ética en Investigación , Humanos , Internet , Estudios Longitudinales , Investigadores , Sujetos de Investigación , Encuestas y Cuestionarios , Estados Unidos
4.
J Prof Nurs ; 28(5): 284-90, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23006650

RESUMEN

The purpose of this article is to present findings from a study which evaluated the effectiveness of a virtual community (an emerging pedagogical application) on student engagement and academic performance. Virtual communities mirror real-life through unfolding patient histories and relationship development over time. Students also become more engaged in learning by creating personally meaningful knowledge of a concept (Rogers & Stone, 2007). Virtual communities offer one teaching strategy to assist students in learning complex, health-related content in a contextualized manner. This quasi-experimental study involved first-semester baccalaureate nursing students enrolled in a course at two campuses of a nursing program at a large university in the Southwest. Three key strategies assessed the impact of the virtual community on student engagement and learning: third-party observational measurement, end-of-class student/faculty surveys, and use of knowledge items in student exams for the class. Significant differences between the control and experimental group were found regarding learning engagement and communication exchanges; the groups appeared similar in ratings of quality of instruction and academic performance. Use of virtual communities can help nursing educators address the recent Carnegie Foundation study's (Benner, Sutphen, Leonard & Day, 2010) counsel to implement "pedagogies of contextualization" in which theoretical and factual information about diseases and conditions are placed in the context of a patient's experience.


Asunto(s)
Instrucción por Computador/métodos , Bachillerato en Enfermería/métodos , Modelos Educacionales , Estudiantes de Enfermería , Interfaz Usuario-Computador , Adulto , Recolección de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación en Evaluación de Enfermería , Adulto Joven
5.
J Transcult Nurs ; 23(2): 198-204, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22294335

RESUMEN

PURPOSE: Cultural competence is an expectation of professional practice, yet effectively teaching this concept to nursing students is challenging. The purpose of this study was to assess the use of a virtual community as a teaching application to foster cultural awareness among nursing students. METHOD: This correlational study involved the collection of two surveys from 342 first-semester students from five baccalaureate nursing programs that used The Neighborhood virtual community during one semester. Descriptive and comparative analyses were performed. FINDINGS: Results suggest that use of the virtual community may have contributed to cultural awareness among student participants. There was a significant correlation between frequency of use and cultural awareness. Virtual communities may represent a useful teaching application for cultural competence in nursing education. Further research is needed to specifically test cultural competence education strategies using a virtual community platform.


Asunto(s)
Concienciación , Competencia Cultural , Bachillerato en Enfermería/métodos , Características de la Residencia , Estudiantes de Enfermería/psicología , Interfaz Usuario-Computador , Adulto , Análisis de Varianza , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Facultades de Enfermería , Estadística como Asunto , Adulto Joven
6.
Dent Update ; 38(5): 327-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21834313

RESUMEN

Swellings and tumours within the oral cavity are a common finding, however, benign intra-oral schwannoma or neurolemma is relatively uncommon, especially in younger patients. Involvement of the palate is a rare presentation although there have been a few reported cases relating to the lingual and other tissues. This paper reviews intra-oral schwannomas and presents a case of such a tumour of the soft palate in a paediatric patient and discusses the presenting features, differential diagnoses, along with the management of the condition.


Asunto(s)
Neurilemoma/diagnóstico , Neoplasias Palatinas/diagnóstico , Paladar Blando/patología , Biopsia , Niño , Estudios de Seguimiento , Humanos , Masculino
7.
J Antimicrob Chemother ; 65(3): 442-5, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20089543

RESUMEN

OBJECTIVES: To describe the emergence of linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) of sequence type (ST)36 lineage in two paediatric patients with cystic fibrosis, after long-term low-dose linezolid treatment. METHODS: Two paediatric males with cystic fibrosis had sputum samples quantitatively cultured during hospitalization. After the isolation of MRSA from both patients, oral treatment with 300 mg linezolid twice daily was initiated for periods of 1-2 months separated by up to 6 months. Isolates cultured 9 months after the start of treatment were tested for resistance to linezolid by agar dilution (BSAC). Resistant isolates were examined for 23S rDNA mutations, and typed by phage and macrorestriction with SmaI. Isolates from follow-up sputum samples were obtained until 44-51 months after treatment with linezolid. RESULTS: Colonization with MRSA was at a density of approximately 10(6) cfu/mL sputum for both subjects. Initial isolates were susceptible to linezolid, but, 9 months later, isolates from both patients were resistant (MICs > 16 mg/L). Both isolates were epidemic MRSA-16 variant A1 (ST36-MRSA-II), which is widespread in UK hospitals. Both isolates were heterozygous for a G2576T mutation in their 23S rDNA genes, but one was resistant to fusidic acid and tetracycline. In follow-up sampling, the younger patient yielded linezolid-resistant EMRSA-16 for a further 42 months, whilst the other lost the linezolid-resistant MRSA and had alternately Pseudomonas aeruginosa or linezolid-susceptible EMRSA-16 variant A1 isolated over 35 further months. CONCLUSIONS: Linezolid resistance emerged in two isolates of ST36 MRSA colonizing the lungs of two paediatric cystic fibrosis patients. Subtherapeutic levels of linezolid may have facilitated the selection of resistance.


Asunto(s)
Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Fibrosis Quística/complicaciones , Farmacorresistencia Bacteriana , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Oxazolidinonas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Adolescente , Técnicas de Tipificación Bacteriana , Tipificación de Bacteriófagos , Niño , Dermatoglifia del ADN , Genes de ARNr , Humanos , Linezolid , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Mutación , Polimorfismo de Longitud del Fragmento de Restricción , Pseudomonas aeruginosa/aislamiento & purificación , ARN Bacteriano/genética , ARN Ribosómico 23S/genética , Esputo/microbiología , Reino Unido
8.
J Man Manip Ther ; 17(4): 247-54, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20140156

RESUMEN

A temporomandibular disorder (TMD) is a very common problem affecting up to 33% of individuals within their lifetime. TMD is often viewed as a repetitive motion disorder of the masticatory structures and has many similarities to musculoskeletal disorders of other parts of the body. Treatment often involves similar principles as other regions as well. However, patients with TMD and concurrent cervical pain exhibit a complex symptomatic behavior that is more challenging than isolated TMD symptoms. Although routinely managed by medical and dental practitioners, TMD may be more effectively cared for when physical therapists are involved in the treatment process. Hence, a listing of situations when practitioners should consider referring TMD patients to a physical therapist can be provided to the practitioners in each physical therapist's region. This paper should assist physical therapists with evaluating, treating, insurance billing, and obtaining referrals for TMD patients.

9.
Dent Traumatol ; 24(1): 65-9, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18173669

RESUMEN

The purpose of the study was to assess the current opinions and usage of mineral trioxide aggregate (MTA) for apical barrier formation of non-vital immature permanent teeth by consultants in paediatric dentistry in the UK. A semi-structured postal questionnaire was sent to all known consultants in paediatric dentistry in the UK. The response rate was 78.6% (44 of 56). Thity-eight consultants (86.3%) agreed that the use of this material was a good idea with 68.2% having used or arranged for its use in apical barrier formation. Forty-two consultants (95.5%) agreed that reduced number of visits was an advantage to the technique, with only 34.1% agreeing that this procedure was less likely to weaken the tooth and 63.6% agreed that material and equipment costs were a drawback and 50% agreed that lack of available evidence was a disadvantage to its use. The results from this study give an indication of the extent of MTA use by consultant-led services in paediatric dentistry in the UK and highlights the need for a multi-centre randomised controlled clinical trial.


Asunto(s)
Compuestos de Aluminio/uso terapéutico , Actitud del Personal de Salud , Compuestos de Calcio/uso terapéutico , Odontólogos , Incisivo/efectos de los fármacos , Óxidos/uso terapéutico , Odontología Pediátrica , Pautas de la Práctica en Odontología , Materiales de Obturación del Conducto Radicular/uso terapéutico , Tratamiento del Conducto Radicular/métodos , Silicatos/uso terapéutico , Ápice del Diente/efectos de los fármacos , Diente no Vital/terapia , Compuestos de Aluminio/economía , Fenómenos Biomecánicos , Compuestos de Calcio/economía , Dentina Secundaria/inducido químicamente , Combinación de Medicamentos , Humanos , Incisivo/patología , Óxidos/economía , Materiales de Obturación del Conducto Radicular/economía , Tratamiento del Conducto Radicular/economía , Silicatos/economía , Estrés Mecánico , Encuestas y Cuestionarios , Ápice del Diente/patología , Reino Unido
10.
Dent Traumatol ; 23(6): 328-32, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17991231

RESUMEN

Alveolar bone resorption is an inevitable consequence of tooth loss and may be detrimental to long-term dental aesthetics and function. The aim of the present study was to quantify the degree of tissue resorption following the loss of a permanent incisor in a young population. The study group comprised 11 boys and five girls who all required the extraction of a permanent maxillary central incisor due to trauma-related sequelae. Mean age at tooth loss was 10.8 years. Upper alginate impressions were taken at regular intervals following tooth loss and were cast in yellow dental stone. Study models were sectioned longitudinally through the mid-point of both the maxillary incisor socket and the contra-lateral incisor to provide a thin plaster section. Digital photographs were acquired of the edentulous (A1) and dentate (A2) surfaces of this section and image analysis software was employed to quantify the surface area of both A1 and A2. At 3 months postextraction, mean A1 was 15.7% less than mean A2. By 6 months mean A1 had further reduced and was 25.3% less than that of the corresponding dentate alveolus. However, at subsequent time intervals following tooth extraction (>6 months), tissue loss appeared to stabilise with an overall reduction in tissue area remaining at 22%. This reduction in supporting tissue area was found to be highly statistically significant (P = 0.002, anova). Furthermore, girls appeared to have an overall greater degree of tissue loss than boys (P = 0.015). Further research is indicated to explore factors influencing the degree of tissue loss following incisor extraction and the benefit of therapeutic interventions in limiting this resorption.


Asunto(s)
Pérdida de Hueso Alveolar/etiología , Incisivo/lesiones , Enfermedades Maxilares/etiología , Pérdida de Diente/complicaciones , Niño , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Modelos Dentales , Factores Sexuales
11.
Int J Paediatr Dent ; 17(2): 105-9, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17263860

RESUMEN

OBJECTIVES: The purpose of this study was to monitor the effect of an interruption in a service for children who were scheduled to have dental extractions under general anaesthesia (GA). The reasons for offering GA and the treatment given while the service was not available, together with the history of the pain, antibiotic usage and alterations to the number of teeth extracted were recorded. METHODS: When the GA extraction service stopped, the children who were scheduled to have their teeth extracted were placed on a waiting list. When the service recommenced 6 months later, the children were invited to attend a reassessment. Relevant data were collected at this visit using a proforma. RESULTS: A total of 321 children had their extractions delayed. Only 249 of these attended for a reassessment. During the waiting period, 102 parents (41.0%) reported that their children required analgesics, 71 (28.5%) stated that their children's sleep was disturbed and 82 (32.9%) recorded problems with eating. One hundred and twenty-three children (49.4%) had received antibiotics, with 49 (19.6%) having been prescribed two or more courses. The majority of treatment plans (85.5%) remained unchanged. CONCLUSIONS: Many children who had had their extractions delayed suffered further pain and disruption to their life.


Asunto(s)
Anestesia Dental/métodos , Anestesia General/estadística & datos numéricos , Atención Dental para Niños/métodos , Extracción Dental , Odontalgia/tratamiento farmacológico , Analgésicos/administración & dosificación , Antibacterianos/administración & dosificación , Niño , Preescolar , Inglaterra , Femenino , Odontología General/legislación & jurisprudencia , Política de Salud , Humanos , Masculino , Listas de Espera
12.
Int J Paediatr Dent ; 17(2): 139-44, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17263866

RESUMEN

BACKGROUND: The Central Giant Cell Granuloma (CGCG) is an uncommon benign lesion of the jaws. It occurs predominantly in children and young adults, and may cause local destruction of bone and displacement of teeth. CASE REPORT: Two case reports are presented illustrating the joint management of children with this condition by paediatric dentistry and maxillofacial surgery teams. CONCLUSION: The role of the paediatric dental team is extensive in children with CGCG and coordination of care from both teams is essential to ensure that the highest quality of care is provided.


Asunto(s)
Granuloma de Células Gigantes/cirugía , Enfermedades Mandibulares/cirugía , Enfermedades Maxilares/cirugía , Niño , Humanos , Masculino , Grupo de Atención al Paciente
13.
Int J Paediatr Dent ; 17(2): 145-50, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17263867

RESUMEN

BACKGROUND: This report presents a case of leukaemic infiltration of the mandible in a 10-year-old female of Sudanese extraction. CASE REPORT: The patient was in remission from acute lymphoblastic leukaemia when she presented with pain localized to the alveolar ridge overlying the unerupted lower right second permanent molar. Two days later, she developed right inferior alveolar nerve paraesthesia. Radiographic imaging demonstrated cortical line absence around the developing lower right second and third permanent molars, and distal displacement of the lower right third molar. In addition, the cortical outline of the right inferior dental canal lacked clarity. Biopsy confirmed leukaemia recurrence demonstrating the Philadelphia chromosome. Tailored chemotherapy was commenced, and a bone marrow transplant was carried out 12 weeks later. At 6-month dental review, the patient remained exceptionally well with no bone pain and normal sensation in the right lower lip. CONCLUSION: The importance of regular and long-term dental examination of patients with leukaemia is discussed.


Asunto(s)
Infiltración Leucémica/patología , Mandíbula/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas , Trasplante de Médula Ósea , Niño , Dexametasona/administración & dosificación , Femenino , Humanos , Mesilato de Imatinib , Infiltración Leucémica/tratamiento farmacológico , Infiltración Leucémica/genética , Infiltración Leucémica/cirugía , Cromosoma Filadelfia , Piperazinas/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Pirimidinas/administración & dosificación
14.
15.
Methods Mol Biol ; 373: 103-14, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17185761

RESUMEN

Resistance to oxazolidinone antibiotics, including linezolid, in Gram-positive bacteria is mediated by single-nucleotide polymorphisms (SNPs) in the 23S ribosomal RNA. A G2576U change (encoded by a G2576T mutation in the rRNA genes) is found in most resistant clinical isolates of enterococci and staphylococci; a variety of changes have been found in resistant mutants selected in vitro. Pyrosequencing can be used to detect SNPs known to confer oxazolidinone resistance, including the G2576T change. Most bacteria have more than one rRNA gene copy and Pyrosequencing can also be used for allele quantification, i.e., to estimate the proportions of mutant vs wild-type alleles. The number of mutated rRNA gene copies correlates roughly with the level of oxazolidinone resistance displayed by resistant isolates. This chapter summarizes the Pyrosequencing assays that have been developed in our laboratory for analyzing oxazolidinone-resistant enterococci and staphylococci.


Asunto(s)
Farmacorresistencia Microbiana/genética , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/genética , Mutación/genética , Oxazolidinonas/farmacología , Secuencia de Bases , Biotinilación , Cartilla de ADN/metabolismo , ADN Bacteriano/análisis , ADN Bacteriano/genética , Difosfatos/metabolismo , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADN , Moldes Genéticos
16.
Dent Update ; 33(10): 608-10, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17209535

RESUMEN

Double teeth in the permanent dentition have a reported incidence of 0.1% for Caucasian groups. Common associated problems include adverse aesthetics, caries, periodontal disease, and malocclusions. Management can be challenging, often requiring a multidisciplinary approach. Three cases are presented illustrating the variety of treatments available.


Asunto(s)
Restauración Dental Permanente/métodos , Dientes Fusionados/terapia , Incisivo/anomalías , Niño , Resinas Compuestas , Cavidad Pulpar/anomalías , Femenino , Dientes Fusionados/cirugía , Humanos , Incisivo/cirugía , Masculino , Planificación de Atención al Paciente , Extracción Dental
17.
Stud Health Technol Inform ; 111: 362-4, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15718760

RESUMEN

The primary goal of this study was to establish an objective baseline for subjects who participated in a study in an immersed environment created for the virtual reality therapy (VRT) situation. Since the effects of VRT on the subjects treated for neurosis have traditionally been measured by subjective measurements, there is a need to include objective measures. This will improve and validate the effectiveness of VRT. Fifteen college students participated in this study. Specifically, the researchers measured the activity of the subjects' brainwaves in response to the VRT using EEG technology. The preliminary data indicated that, in most cases, subjects had a decline in brain wave activity between what is deemed a normal / baseline brain activity and the brainwave activity recorded when they were when they were connected to the virtual reality equipment and under influence of an immersive scene. In rare instances, there were some subjects that showed extreme increases in brain activities. In addition, the data indicated that, in most cases, subjects are more relaxed while under the immersive influence with respect to brain activities than those that are not.


Asunto(s)
Encéfalo/fisiología , Diagnóstico por Computador , Interfaz Usuario-Computador , Electroencefalografía , Humanos , Investigación
18.
Stud Health Technol Inform ; 98: 278-80, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15544289

RESUMEN

This pilot study is the first known in-depth case study of the effectiveness of virtual reality therapy (VRT) as a treatment for Test Anxiety (TA). The subject of the study was a 28-year-old male, whose anxiety and avoidance behavior was interfering with his normal academic activities. For treatment, he was placed in a virtual classroom and later in a virtual auditorium. The subject was exposed to six moderately increasing in difficulty level virtual situations. The subject rated each situation for discomfort. As a simple measure of anxiety, a modified version of the Subjective Units of Disturbance (SUD) scale was used every five minutes during exposure. This case study showed VRT to be an effective treatment method for reducing self-reported TA. Symptoms experienced by the subject during VRT sessions were just as real to the subject as actual test taking and general TA situations. They included increased heart rate, mild dizziness, and headaches. This case study of TA indicates that VRT may be used as an effective treatment method for reducing self-reported anxiety and improving the performance of subject(s) who suffer from TA.


Asunto(s)
Ansiedad/prevención & control , Interfaz Usuario-Computador , Adulto , Georgia , Humanos , Masculino
19.
Antimicrob Agents Chemother ; 47(10): 3061-6, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14506009

RESUMEN

Mutations in mutS and mutL, which encode DNA mismatch repair (MMR) proteins, can confer hypermutator phenotypes and may facilitate the emergence of mutational antibiotic resistance in bacteria. Linezolid-resistant enterococci (LRE) rarely emerge during therapy and contain mutations in 23S rRNA genes. As enterococci with defective MMR could be prone to the development of oxazolidinone resistance mutations, we investigated 13 clinical isolates of Enterococcus faecium, including 2 LRE, for mutations in mutSL. A 4,944-bp fragment spanning mutSL was sequenced from two pairs of linezolid-resistant (MICs, 64 micro g/ml) and linezolid-susceptible (MICs, 2 micro g/ml) E. faecium isolates (one pair from Austria and one pair from the United Kingdom) identical by pulsed-field gel electrophoresis. The pairs represented distinct strains in which linezolid resistance had emerged during therapy. The MutSL peptides of all four isolates had amino acid substitutions compared with the sequence of E. faecium strain DO (used for genome sequencing). These were Val352Ile (one pair of isolates only) and Met628Leu in MutS and Leu387Pro, Tyr406Phe, Thr415Ser, Phe427Leu, and Phe565Ile in MutL. The significance of these changes remains unknown; these isolates did not show a demonstrable hypermutator phenotype. The same substitutions were found in two of nine geographically diverse linezolid-susceptible enterococcal isolates; the other seven isolates had MutSL sequences identical to that of strain DO. Multilocus sequence typing revealed that all isolates with alternate MutSL peptides belonged to a distinct lineage of a prevalent E. faecium clonal complex, designated CC17. Further studies are needed to investigate the prevalence of these MutSL mutations and their possible roles in the emergence of E. faecium strains resistant to oxazolidinones and other antibiotic classes.


Asunto(s)
Adenosina Trifosfatasas/genética , Proteínas Bacterianas/genética , Proteínas de Unión al ADN/genética , Farmacorresistencia Bacteriana/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Proteínas de Escherichia coli/genética , Mutación , Oxazolidinonas/farmacología , Acetamidas/farmacología , Sustitución de Aminoácidos , Disparidad de Par Base/genética , Secuencia de Bases , Reparación del ADN/genética , Electroforesis en Gel de Campo Pulsado , Enterococcus faecium/clasificación , Frecuencia de los Genes , Variación Genética , Linezolid , Proteínas MutL , Proteína MutS de Unión a los Apareamientos Incorrectos del ADN
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