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.

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