Pathogenesis of gram-positive bacterial endophthalmitis

The severity of endophthalmitis has been associated generally with the viru lence of the offending pathogen. However, precisely what constitutes the vi rulence in intraocular infections remains ill defined. We therefore sought to identify the basis for virulence for three common ocular pathogens (Baci llus cereus, Enterococcus faecalis, and Staphylococcus aureus) in terms ofi ntraocular growth rates, bacterial localization patterns, and the contribut ion of cell nails and secreted products to the pathogenesis of endophthalmi tis. Rabbit eyes were injected intravitreally with (ii) viable B. cereus, E . faecalis, or S. aureus, (ii) metabolically inactive B. cereus, E. faecali s, or S. aurens, (iii) sacculus preparations from each strain, or (iv) cult ure fluid containing products secreted by each strain. Eyes were assessed a t various times following injection by slit lamp biomicroscopy, electroreti nography ERG, bacterial and inflammatory cell enumeration, and histology. B , cereus endophthalmitis followed a more rapid and virulent course than E. faecalis or S. aureus endophthalmitis, eliminating retinal responsiveness, as measured by ERG, by 12 h. Analysis of bacterial localization revealed th at B. cereus uniquely migrated rapidly from posterior to anterior segment d uring infection. Although injection of neither metabolically inactive bacte ria nor cell wall sacculi greatly affected ERG, significant intraocular inf lammation was observed. Injection of B. cereus or S. aurens culture fluids caused both significant reductions in retinal responsiveness and significan t intraocular inflammation, paralleling that seen in natural infections. Th e results demonstrate that toxins, intraocular localization, and, to a less er extent, the intraocular host response to cell walls all contribute to th e pathogenesis of B. cereus, S. aureus, and E. faecalis endophthalmitis in a pathogen-specific manner. The key pathophysiologic differences in these i ntraocular diseases highlight opportunities for optimizing conventional the rapies and deriving new ones.