A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases.

Infectious keratitis is a vision-threatening microbial infection. The increasing antimicrobial resistance and the fact that severe cases often evolve into corneal perforation necessitate the development of alternative therapeutics for effective medical management. Genipin, a natural crosslinker, was recently shown to exert antimicrobial effects in an ex vivo model of microbial keratitis, highlighting its potential to serve as a novel treatment for infectious keratitis. This study aimed to evaluate the antimicrobial and anti-inflammatory effects of genipin in an in vivo model of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) keratitis. Clinical scores, confocal microscopy, plate count, and histology were carried out to evaluate the severity of keratitis. To assess the effect of genipin on inflammation, the gene expression of pro- and anti-inflammatory factors, including matrix metalloproteinases (MMPs), were evaluated. Genipin treatment alleviated the severity of bacterial keratitis by reducing bacterial load and repressing neutrophil infiltration. The expression of interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 15 (IL15), tumor necrosis factor-α (TNF-α), and interferon γ (IFNγ), as well as MMP2 and MMP9, were significantly reduced in genipin-treated corneas. Genipin promoted corneal proteolysis and host resistance to S. aureus and P. aeruginosa infection by suppressing inflammatory cell infiltration, regulating inflammatory mediators, and downregulating the expression of MMP2 and MMP9.

Genipin in an Ex Vivo Corneal Model of Bacterial and Fungal Keratitis.

Purpose: To determine whether genipin (a natural crosslinker) could reduce the colonization and proliferation of bacteria and fungi in an ex vivo model of corneal infection. Methods: This study, using an ex vivo model of bacterial and fungal keratitis, investigated the antimicrobial efficacy of genipin crosslinking. Excised corneoscleral buttons were wounded by scalpel incision and subsequently infected with Staphylococcus aureus, Pseudomonas aeruginosa, or Candida albicans. After inoculation, corneas were treated with genipin for 24 hours at 37°C. Histologic examinations were carried out, and the number of viable colony-forming units (CFU)/cornea was determined. Results: Genipin exerts bactericidal action against S. aureus and P. aeruginosa, as well as fungicidal action against C. albicans and significantly reduced the CFU compared to contralateral eyes that received saline treatment (P < 0.05). Conclusions: These data identify genipin as a novel ocular antimicrobial agent that has the potential to be incorporated into the therapeutic armamentarium against microbial keratitis. Translational Relevance: This study provided evidence for the antimicrobial and antifungal properties of genipin as an alternative crosslinker that could be used in the management of infectious keratitis.

[Prevalence and risk factors associated to tuberculosis and non-tuberculous mycobacterial infections in HIV-positive patients in Bogotá].

INTRODUCTION: Tuberculosis is one of the most widely distributed infectious diseases worldwide. It is the most common cause of mortality among AIDS patients. In Colombia, 12,918 tuberculosis cases were notified, and 926 deaths were reported in 2015. OBJECTIVE: To determine the prevalence and risk factors associated to mycobacterial infections in HIVpositive patients in two public hospitals from Bogotá. MATERIALS AND METHODS: A prospective and descriptive study was carried out by an active search for tuberculosis cases and non-tuberculous mycobacterial infections in HIV-positive patients. We considered demographic, social, clinical, and personal habits as variables. Statistical analyses were done using Stata 13™ software. RESULTS: Three hundred and fifty six patients were included, 81.2% were men and 18.8% were women; the mean age was 36.5 years. Tuberculosis infection had a frequency of 19.9% (95% CI: 15.9-24.5%) and non-tuberculous mycobacterial infection had a 3.9% frequency (95% CI: 2.16-6.5%). Bivariate analysis showed a statistically significant association between tuberculosis infection and CD4+ T cell counts (p=0.003), viral load (p=0.008), antiretroviral therapy (p=0.014), and body mass index (BMI) <18 kg/m2 (p=0.000). In non-tuberculous mycobacterial infections there was a statistically significantassociation with BMI (p=0.027) and CD4+ T cell counts (p=0.045). CONCLUSION: Factors associated with an impaired immune system caused by HIV infection are an important risk factor for developing tuberculosis. The lack of antiretroviral therapy and the BMI were also important risk factors for tuberculosis.

Prevalencia y factores asociados a la tuberculosis y las micobacteriosis en pacientes positivos para HIV en Bogotá / Prevalence and risk factors associated to tuberculosis and non-tuberculous mycobacterial infections in HIV-positive patients in Bogotá

Resumen Introducción. La tuberculosis es una de las enfermedades infecciosas de más amplia distribución en el mundo y constituye una de las primeras causas de muerte en pacientes con sida. En Colombia, en el 2015, se notificaron 12.918 casos de tuberculosis y 926 muertes. Objetivo. Determinar la prevalencia y los factores asociados a infecciones micobacterianas en pacientes infectados con el virus de inmunodeficiencia humana (HIV) en dos hospitales públicos de Bogotá. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal con búsqueda activa de casos de tuberculosis y micobacteriosis en pacientes positivos para HIV. Se estudiaron variables demográficas, sociales, clínicas y de hábitos personales. Los análisis estadísticos se hicieron con el programa Stata 13TM. Resultados. Se incluyeron en el estudio 356 pacientes: 81,2 % hombres y 18,8 %, mujeres, con una media de edad de 36,5 años. La frecuencia de la tuberculosis fue de 19,9 % (IC95% 15,9-24,5 %) y la de infecciones por micobacterias no tuberculosas, de 3,9 % (IC95% 2,16-6,5 %). El análisis bivariado evidenció una asociación estadísticamente significativa entre la tuberculosis y el conteo de linfocitos TCD4+ (p=0,003), la carga viral (p=0,0008), el tratamiento antirretroviral (p=0,017) y un índice de masa corporal (IMC) menor de 18 kg/m2 (p=0,000). En las micobacteriosis solamente se presentó asociación estadísticamente significativa con el IMC (p=0,017) y con el conteo de linfocitos TCD4+ (p=0,045). Conclusión. Los factores asociados al deterioro del sistema inmunitario causados por el HIV, así como el no administrar el tratamiento antirretroviral de gran actividad y el IMC, constituyeron factores de riesgo para desarrollar la tuberculosis.

Abstract Introduction. Tuberculosis is one of the most widely distributed infectious diseases worldwide. It is the most common cause of mortality among AIDS patients. In Colombia, 12,918 tuberculosis cases were notified, and 926 deaths were reported in 2015. Objective. To determine the prevalence and risk factors associated to mycobacterial infections in HIV-positive patients in two public hospitals from Bogotá. Materials and methods. A prospective and descriptive study was carried out by an active search for tuberculosis cases and non-tuberculous mycobacterial infections in HIV-positive patients. We considered demographic, social, clinical, and personal habits as variables. Statistical analyses were done using Stata 13TM software. Results. Three hundred and fifty six patients were included, 81.2% were men and 18.8% were women; the mean age was 36.5 years. Tuberculosis infection had a frequency of 19.9% (95% CI: 15.9-24.5%) and non-tuberculous mycobacterial infection had a 3.9% frequency (95% CI: 2.16-6.5%). Bivariate analysis showed a statistically significant association between tuberculosis infection and CD4+ T cell counts (p=0.003), viral load (p=0.008), antiretroviral therapy (p=0.014), and body mass index (BMI) <18 kg/m2 (p=0.000). In non-tuberculous mycobacterial infections there was a statistically significant association with BMI (p=0.027) and CD4+ T cell counts (p=0.045). Conclusion. Factors associated with an impaired immune system caused by HIV infection are an important risk factor for developing tuberculosis. The lack of antiretroviral therapy and the BMI were also important risk factors for tuberculosis.

Staphylococcus aureus resistente a la vancomicina: una nueva amenaza / Vancomycin resistant Staphylococcus aureus: a new threat

Staphylococcus aureus resistente a la vancomicina (Vancomycin resistant Staphylococcus aureus, VRSA) es una causa emergente de infección en el ambiente hospitalario. Para una adecuada detección, los laboratorios deben utilizar métodos especiales de evaluación y de susceptibilidad. Algunos de estos métodos son altamente específicos, mientras que otros necesitan pruebas adicionales para definir un resultado. Actualmente, existen tres casos de VRSA descritos en los Estados Unidos; en Suramérica, 5 casos de aislamientos de Staphylococcus aureus con resistencia intermedia a la vancomicina (Vancomycin intermediate Staphylococcus aureus, VISA), y en Colombia no se han presentado los primeros reportes de VISA/VRSA.Entre los factores de riesgo para la adquisición de VISA/ VRSA está la alta prevalencia de Staphylococcus aureus resistente a la meticilina (Methicillin resistant Staphylococcus aureus, MRSA) y el alto consumo de vancomicina. Sin una vigilancia epidemiológica, un control de infecciones, el adecuado uso de los antibióticos y una coordinación entre las autoridades de salud pública y los hospitales, los niveles de VRSA probablemente irán en incremento. El objetivo de este artículo es revisar los aspectos epidemiológicos, los mecanismos de resistencia, el proceso diagnóstico, las opciones terapéuticas y las medidas de control de infecciones para detener el desarrollo del VRSA