Individual variation is the key to the development of a vaccine against Staphylococcus aureus: a comparative study between mice lineages

Bacterial infections occur worldwide and are a major public health problem. Among pathogens, Staphylococcus aureus is the main causative agent of bacterial diseases in the world. This study aimed to evaluate which components of the immune system could act protectively against a S. aureus infection in intradermally immunized mice. C57BL/6 and A/j mice were immunized intradermally with S. aureus inactivated by heat and then challenged with viable strains in an air pouch model. At 6, 12, and 24 h after the challenge, euthanasia was performed, and the cellular profile of the inflammatory infiltrate, cytokines, and the bacterial load were evaluated in the air pouch lavages. Immunized mice demonstrated that the intradermal immunization with S. aureus promoted protection in C57BL/6 mice by reducing the bacterial, which was correlated with increased serum concentration of IgG antibodies (IgG1 and IgG2a) against S. aureus. The increase in IgG2a antibody levels was correlated with a decrease of bacterial load in intradermally immunized C57BL/6 mice, along with production of IL-17A at the inflammation site, as well as IgG1consumption. Similar results were not found in the A/j lineage. In conclusion, a vaccine against S. aureus should focus more on the individual characteristics of the host because it is a determinant factor for the success of the immunization.

Elementos de interés clínico en la microbiología molecular de Staphylococcus aureus / Elements of clinical interest in the molecular microbiology of Staphylococcus aureus

El Staphylococcus aureus es uno de los microorganismos de mayor importancia en la asistencia médica, emergente en la comunidad y en el medio hospitalario. El objetivo de este trabajo es presentar una actualización sobre los elementos de interés clínico de la microbiología molecular del Staphylococcus aureus. Para confeccionar esta revisión se utilizaron las bases de datos de Scielo, HINARI, Pubmed-Medline y bibliografías disponibles sobre el tema y los descriptores empleados fueron: Staphylococcus aureus, resistencia a la meticilina, genes, epidemiología molecular, virulencia y la combinación entre ellos. Se revisaron los elementos que determinan sus factores de virulencia, la resistencia antimicrobiana, la versatilidad de estrategias patogénicas, la capacidad de sobrevivir en diferentes condiciones, la evolución y virulencia de los procesos que produce. Igualmente se abordó el diagnóstico de la resistencia, las técnicas de diagnóstico molecular, con sus utilidades, limitaciones, ventajas y desventajas y los estudios de estos temas en los últimos años en Cuba, pues circulan cepas de Staphylococcus aureus resistentes a la meticilina, pero no se conoce la situación real. Se recomienda la conveniencia y necesidad de organizar y armonizar estudios clínicos, epidemiológicos y microbiológicos, que puedan mostrar cuál es la situación actual de este microorganismo y sus infecciones, que aporten datos de su evolución molecular, para evaluar la tendencia de la situación encontrada, que permitan decisiones para el desarrollo de programas de vigilancia y control y revitalicen los medios y métodos de diagnóstico. Resulta importante el conocimiento actualizado del tema, la interpretación de nuevos resultados y el intercambio científico(AU)

Staphylococcus aureus is one of the most important microorganisms in medical care, emerging in the community and in the hospital environment. The objective of this work is to present an update on the elements of clinical interest of the molecular microbiology of Staphylococcus aureus. To make this review, the databases of Scielo, HINARI, Pubmed-Medline and bibliographies available on the subject were used and the descriptors used were: Staphylococcus aureus, methicillin resistance, genes, molecular epidemiology, virulence and the combination between them. We reviewed the elements that determine its virulence factors, antimicrobial resistance, the versatility of pathogenic strategies, the ability to survive in different conditions, the evolution and virulence of the processes it produces. Likewise, the diagnosis of resistance, molecular diagnostic techniques, with their utilities, limitations, advantages and disadvantages, and the studies of these subjects in recent years in Cuba were addressed, since methicillin-resistant strains of Staphylococcus aureus circulate, but not the real situation is known. It is recommended the convenience and need to organize and harmonize clinical, epidemiological and microbiological studies, which can show what is the current situation of this microorganism and its infections, that provide data of its molecular evolution, to evaluate the tendency of the situation found, that allow decisions for the development of surveillance and control programs and revitalize the means and methods of diagnosis. Current knowledge of the subject, interpretation of new results and scientific exchange is important(AU)

Factores de riesgo asociados a infecciones por Staphylococcus aureus meticilino resistente en pacientes con neumonía adquirida en la comunidad asistidos en terapia intensiva / RISK FACTORS ASSOCIATED WITH METHICILLIN STAPHYLOCOCCUS AUREUS RESISTANT IN PATIENTS WITH ACQUIRED PNEUMONIA IN THE COMMUNITY, ASSISTED AT INTENSIVE CARE UNITS

Introducción: La incidencia creciente de infecciones invasivas por Staphylococcus aureus meticilino-resistente adquirido en la comunidad (SAMR-AC) obliga a considerar a este patógeno como posible agente etiológico de la neumonía adquirida en la comunidad (NAC). Es importante reconocer variables específicas que se asocien con un mayor riesgo de padecer esta enfermedad, a fin de mejorar la terapia antibiótica empírica y limitar el tratamiento anti-SAMR. Objetivos: Identificar factores de riesgo asociados a SARM-AC en pacientes con NAC hospitalizados en Unidades de Cuidados Intensivos (UCI). Materiales y métodos: Se analizaron de manera retrospectiva todos los episodios de NAC ingresados en la UCI de un hospital público entre los años 2006 y 2014 en los que se logró identificar el agente etiológico. Se dividió a la población en dos grupos según el agente causal: SAMR-AC (NAC-S) o no SAMR-AC (NAC- no S). Se compararon diferentes variables demográficas, epidemiológicas y clínicas entre ambos grupos (análisis univariado). Para identificar factores de riesgo asociados con NAC por SAMR-AC se realizó análisis de regresión logística de las variables que resultaron significativamente diferentes en el análisis univariado. Para valorar diferencias entre ambos grupos se utilizó estadística descriptiva, test de Fisher y análisis de regresión logística. Se utilizó el software EPIcalc-2000. Se consideró significativo un valor de p<0.05. Resultados: Se incluyeron 239 episodios de NAC, de las cuales 39 fueron causadas por SAMR-AC, y 200 por otros agentes, con la siguiente distribución:niae 6 (3%), H1N1 5 (2,5%), Mycoplasma pneunoniae 4 (2%), Moraxella catharralis 3 (1,5%), SAMS 3 (1,5%), otros 6 (3%). Los pacientes del grupo NAC-S fueron significativamente más jóvenes (edad promedio 35.7 años ± 13.0 vs 43.2 ±12.4, p<0.0001), tuvieron en menor proporción infección por virus de la inmunodeficiencia humana (VIH) (23.1% vs 56.0%, p<0.0001) y presentaron con mayor frecuencia requerimiento de ventilación mecánica (VM) en las primeras 24 horas (38.5% vs 18.0%, p=0.008). Los pacientes del grupo NAC-S mostraron un promedio de score de APACHE II significativamente mayor al ingreso (17.0 ±5.3 vs 13.3 ±4.4, p<0.0001). La mortalidad fue significativamente más elevada en el grupo de NAC-S (35.9% vs 11.0%, p=0.0002). En el resto de las variables analizadas no se observaron diferencias significativas. El análisis de regresión logística mostró que las variables que se asociaron con NAC-S fueron edad ≤35 años (OR 3.60, IC 95% 1.77-7.29), score de APACHE II ≥ 15 (OR 4.37, IC 95% 2.08-9.16) y requerimiento de VM (OR 2.85, IC 95% 1.36-5.86). En cambio, la infección por VIH fue una variable que se asoció con menor probabilidad de desarrollar NAC-S (OR 0.24, IC 95% 0.11-0.52). Conclusión: En los pacientes con NAC que ingresan en una UCI, la edad ≤35 años, el score de APACHE II ≥ 15 y la necesidad de VM se asociaron significativamente con mayor probabilidad de infección por SAMR-AC Streptococcus pneumoniae 113 (56,5%); Haemophillus influenzae 39 (19,5%), Chlamydia psitacii 13 (6,5%), Pseudomonas aeruginosa 8 (4%), Klebsiella pneumo

Risk factors associated with methicillin resistant Staphylococcus aureus community acquired pneumonia in patients assisted at Intensive Care Units Introduction: The increasing incidence of invasive infections by Community Acquired methicilin-resistant Staphylococcus aureus (CA-MRSA) makes it necessary to consider this pathogen as a possible etiological agent in Community Acquired Pneumonia (CAP). It is important to recognize specific variables that are associated with an increased risk of this disease, in order to improve empirical antibiotic therapy and to limit anti-MRSA treatment. Objectives: To identify risk factors associated with CA-MRSA in patients with CAP hospitalized in Intensive Care Units (ICUs). Material and methods: We analyse retrospectively all CAP episodes admitted to the ICU of a public hospital between 2006 and 2014 in which the etiologic agent was identified. The population was divided in two groups, according the etiological agent: CA-MRSA (CAP-MRSA) o not CA-MRSA (CAP-no MRSA). Different demographic, epidemiological and clinical variables were compared between both groups (univariate analysis). Logistic regression analysis of variables that were significantly different in the univariate analysis was performed to identify risk factors associated with CAP by CA-MRSA. Descriptive statistic was used, Fisher´s test was performed to assess differences between both groups and logistic regression test was made to know risks factors associated. EPIcalc-2000 software was used. A value of p <0.05 was considered significant. Results: 239 CAP episodes were includes; 39 were caused by CA-MRSA and 200 by others agents. The etiological distribution was: Streptococcus pneumoniae 113 (56,5%); Haemophillus influenzae 39 (19,5%), Chlamydia psitacii 13 (6,5%), Pseudomona aeruginosa 8 (4%), Klebsiella pneumoniae 6 (3%), H1N1 5 (2,5%), Mycoplasma pneunoniae 4 (2%), Moraxella catharralis 3 (1,5%), MSSA 3 (1,5%), others 6 (3%). Patients in the CAP-MRSA group were significant younger (mean age 35.7 years old ± 13.0 vs 43.2 ±12.4, p<0.0001), had a lower proportion of HIV infections (23.1% vs 56.0%, p<0.0001) and needed of mechanical ventilation (MV) in the first 24 hours with higher frequency (38.5% vs 18.0%, p=0.008). Patients in the CAP-MRSA showed a significantly higher APACHE II score on admission (17.0 ±5.3 vs 13.3 ±4.4, p<0.0001). Mortality rate was significantly higher in CAP-MRSA group (35.9% vs 11.0%, p=0.0002). In the other analysed variables, no significant range differences were observed. Logistic regression analysis showed that the variables that were associated with CAP by MRSA were age ≤35 years (OR 3.60, 95% CI 1.77-7.29), APACHE II score ≥ 15 (OR 4.37, CI 95% 2.08-9.16) and MV requirement (OR 2.85, 95% CI 1.36-5.86). HIV infection was associated with lower probability to have CAP-MSA (OR 0.24, CI 95% 0.11-0.52). Conclusion: In patients with CAP who entered an ICU, age ≤35 years, APACHE II score ≥15 and the need for MV were significantly associated with a greater likelihood of CAP-MRSA infection.

Tratamiento de las infecciones invasivas por Staphylococcus aureus meticilino resistente adquirido en la comunidad / Treatment of invasive infections due to community acquired methicillin resistant Staphylococcus aureus

Las infecciones por Staphylococcus aureus meticilino re-sistente adquirido en la comunidad (SAMR-AC) constituyen un pro-blema emergente debido a su elevada virulencia y gran capacidad de diseminación. Para las infecciones invasivas, las recomendaciones publicadas sugieren vancomicina como droga de elección. Sin em-bargo, no está claro si otras alternativas pudieran ser mejores en de-terminadas situaciones, o si el uso de combinaciones de antibióticos sería beneficioso. No se han realizado trabajos que sugieran que al-guna alternativa terapéutica sea preferible a otra para el tratamiento de pacientes con infecciones invasivas por SAMR-AC, por lo que las decisiones a tomar se basan en la extrapolación de datos de estudios realizados en otros contextos o en la opinión de expertos. Por tal mo-tivo, se presenta esta revisión, con el objeto de poner en manos de los infectólogos y otros especialistas la evidencia disponible, a fin de intentar encontrar las mejores alternativas de tratamiento para estas infecciones

Infections caused to community-acquired methicillin-resistant Staphylococcus aureus ( CA-MRSA ) is an emerging problem due to its high virulence and large capacity of spread. For invasive infections, published recommendations suggest vancomycin as the drug of choice. However, it is unclear whether other alternatives might be better in certain situations, or if the use of combinations of antibiotics would be beneficial. No studies has been done to suggest that any therapeutic alternative is better than another for the treatment of patients with invasive CA-MRSA infections, so the decisions you make are based on extrapolation of data from studies in other contexts or expert opinion. Therefore, this review is presented, in order to put in the hands of infectologist and others specialists the available evidence, in order to find the best treatment options for these infections

Nasal carriage of Panton Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus in healthy preschool children / Colonización nasal de Staphylococcus aureus Meticilino Resistente portador de la Leucocidina Panton-Valentine en preescolares

Objective Determining the prevalence of nasal carriage of S. aureus, both sensitive to methicillin and resistant to it, in preschool children and evaluating the presence of Panton-Valentine leukocidin genes in the isolates. Methods This was a cross-sectional study in which cultures from anterior nares were obtained from healthy preschool children. Isolates were identified as S. aureus based on morphological and biochemical tests. Antibiotic susceptibility profiles were determined by the disk diffusion method. All the isolates were further analyzed by multiplex PCR to determine the presence of mecA and PVL genes; methicillin-resistant isolates were also SCCmec typed by multiplex PCR. Results Overall S. aureus nasal colonization prevalence was 38.5 % and 4.8 % for methicillin-resistant strains. All the methicillin-resistant isolates carried the genes for PVL; two isolates possessed the SCCmec type IV, two were SCCmec type I and one was SCCmec type II. Conclusion This study revealed high PVL-positive, methicillin-resistant S. aureus colonization prevalence in healthy preschool children from Cartagena, which may play a key role in the epidemiology of community-associated infection by methicillin-resistant S. aureus in healthy children from this particular geographical area.

Objetivo Determinar la prevalencia de colonización nasal de S. aureus, tanto sensible como resistente a meticilina, en niños preescolares y evaluar la presencia de los genes de la leucocidina Panton-Valentine en estos aislamientos. Métodos Estudio de corte transversal en el que se realizaron cultivos de flora nasal de niños preescolares. Los aislamientos fueron identificados como S. aureus con base en su morfología y pruebas bioquímicas. La susceptibilidad a antibióticos se determinó por el método de difusión en disco. Todos los aislamientos fueron analizados por PCR múltiple para determinar la presencia de los genes mecA y PVL, y para la tipificación del casete cromosómico SCCmec de los aislamientos resistentes a meticilina. Resultados La colonización nasal por S. aureus fue 38,5 %, y la de cepas meticilino-resistentes fue 4,8 %. Todos los aislamientos SARM portaban los genes para PVL, dos portaban el elemento SCCmec tipo IV, dos fueron tipo I y uno fue tipo II. Conclusión Encontramos una alta prevalencia de colonización por cepas meticilino-resistentes, PVL-positivos en la población estudiada, lo que podría jugar un papel clave en la epidemiología de las infecciones por S.aureus meticilino-resistente en esta área geográfica.

Expression of cell surface markers on methicillin resistant Staphylococcus aureus stimulated lymphocytes.

BACKGROUND & OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) has gradually been increasing, new strategies in the treatment of MRSA infections are required. This depends on the understanding of the infection pathogenesis and the immune response. This study was therefore designed to determine the immune response which develops during MRSA infection and the role of chemokines in this response, and also to compare the results with the changes occurring after MSSA infection. METHODS: The expression of the surface markers of human lymphocytes stimulated by heat-killed MRSA or MSSA was analysed by flow cytometry. The chemokine levels in the lymphocytes culture supernatants stimulated or not stimulated by microorganisms were determined by ELISA. RESULTS: Human peripheral blood mononuclear cells (PBMCs) stimulated by MRSA the levels of CD4(+)CD25(+) regulatory T cells, CD69 expressions in the activated T lymphocytes, CD3(-)CD16(+)CD56(+) NK cells and the levels of MIP-1alpha, MIP-1beta, MCP-1 chemokines increased as compared to the cells not stimulated by MRSA. Although stimulation by MSSA caused an increase in CD25 expression after 24 h, the increase was found to be lower than the one caused by MRSA stimulation. The increase in CD69 expression was statistically significant compared to the cells stimulated by MRSA. Different from the cells stimulated by MRSA, no change was observed in the expressions of CD54 and CD3(-)CD16(+)CD56(+) NK cells in the cells stimulated by MSSA. INTERPRETATION & CONCLUSION: Our findings showed that cellular as well as humoral immunity are critical in MRSA infection and that T cell activation and the increase in chemokines may play a role in the regulation of immune response.