Enterococcus faecalis localization in experimental endophthalmitis: role of plasmid-encoded aggregation substance.

Enterococci have emerged as leading agents of nosocomial infection, yet relatively little is known about the pathogenesis of enterococcal disease. In previous studies, we developed an Enterococcus faecalis endophthalmitis infection model which provides unique opportunities to study the evolution of enterococcal disease by direct observation, as well as through sensitive electrophysiologic measures of organ function. The present study was designed to determine whether E. faecalis possesses traits that permit its attachment to mammalian tissues during infection. It was also of interest to determine whether a plasmid-encoded adhesin, aggregation substance, contributes to enterococcal localization or otherwise mediates adherence to alternate sites. These studies found that, in this model, enterococci attach to membranous structures occurring within the vitreous but that this attachment or the course or severity of disease is unaffected by the aggregation substance phenotype.

Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis.

PURPOSE: To evaluate the contribution of toxins to the severity of Staphylococcus aureus endophthalmitis. METHODS: Experimental endophthalmitis was established by injecting rabbit eyes with wild type S. aureus ISP479 and the isogenic attenuated strain, ISP546, defective in expression of the global regulator locus agr. agr regulates expression of at least 19 exoproteins that are potentially important in the pathogenesis of endophthalmitis. Infections were evaluated using electroretinography, slit lamp biomicroscopy, and histology. Two concentrations (approximately 10 and 1000 organisms) of bacteria were injected. RESULTS: The agr- strain consistently resulted in slower loss of b-wave response when compared to the wild type strain, irrespective of inoculum size. Clinical signs were less severe among the agr- group at 24 and 48 hours when 10 organisms were injected. However, when the number of bacteria injected was increased to 1000, earlier onset of clinical signs was observed, with both groups showing maximum cell and flare and a white fundal reflex at 48 hours after infection. Histologic examination of eyes enucleated 36 hours after inoculation revealed that the wild type strain induced focal retinal destruction and mild vitritis, whereas eyes infected with the agr- strain remained completely normal. Histologic examination carried out when loss of B-wave response was 100% revealed that retinal changes for both groups could not be distinguished. CONCLUSIONS: These data indicate that toxin production by S. aureus contributes to severity of endophthalmitis by accelerating the rate of onset of retinal damage. Therefore, toxin-targeting therapies instituted early in the course of infection could preserve retinal function.

Evaluation of therapeutic measures for treating endophthalmitis caused by isogenic toxin-producing and toxin-nonproducing Enterococcus faecalis strains.

PURPOSE: Management of endophthalmitis typically includes antibiotic combinations to arrest bacterial growth and antiinflammatory agents to limit inflammatory damage to sensitive tissues. Little research has been reported that systematically evaluates the contribution of each therapeutic component for treating infections caused by organisms of varying virulence. The authors determined the relative value of the antinflammatory corticosteroid, dexamethasone, as an intravitreal therapeutic adjunct for the treatment of infection caused by either Enterococcus faecalis expressing a cytolytic toxin previously shown to contribute to the course and severity of infection, or an otherwise identical strain of E. faecalis specifically attenuated in expression of the cytolytic toxin. METHODS: Endophthalmitis in rabbits was monitored using electroretinography (ERG). Eyes were infected with 100 colony forming units of either the cytolytic or the noncytolytic E. faecalis strain. Intravitreal ampicillin and gentamicin were administered at postinfection day 1, and intravitreal dexamethasone was either omitted or administered at day -1, 1, or 1.5. RESULTS: ERG B-wave amplitude declined precipitously throughout the course of infection with cytolytic toxin-producing E. faecalis, despite the administration of antibiotics and regardless of the time of dexamethasone administration. In fact, the ultimate course of infection caused by cytolytic E. faecalis did not differ from the course in untreated controls. In contrast, infections caused by specifically attenuated, noncytolytic strains of E. faecalis responded well to antibiotics augmented by antiinflammatory therapy when the latter was administered either 1 or 1.5 days after the initiation of infection. In these cases, no loss in ERG B-wave response was observed. CONCLUSIONS: These results underscore the importance of bacterial toxins in infectious diseases of the eye and their contribution to treatment failures. These results further suggest that in cases of endophthalmitis caused by toxin producing bacteria, significant improvement in clinical outcome will require specific therapeutic targeting of the toxins involved.