-- Michelle Callegan, Ph.D.
© MPEIR Center, 1998
Epidemiology of bacterial endophthalmitisThe recommended management of B. cereus endophthalmitis includes vitreal aspiration or vitrectomy with intravitreal injection of antibiotics (clindamycin and aminoglycosides) and intravenous antibiotic supplements. Intravitreal vancomycin has been suggested for use in all cases of B. cereus endophthalmitis, primarily because of its broad spectrum for other Gram-positive organisms. Systemic antibiotics (vancomycin, cephalosporins, ciprofloxacin) have been used concurrently for B. cereus endophthalmitis; however, some potentially effective antibiotics (aminoglycosides and vancomycin) do not penetrate readily into the vitreous. The majority of clinical reports on the use of intravitreal or intravenous antibiotics are based on the preferences of the treating physicians and, therefore, give conflicting results about the optimal antibiotic combinations, routes, and duration of therapy for B. cereus endophthalmitis. Recent reports have indicated that the outcome of therapy could be due to several factors, including the age of the patient, the duration between injury and treatment, the antibiotics chosen for therapy, and the condition of the eye upon presentation (e.g., corneal damage, retinal detachment, etc.). Despite aggressive drug and/or surgical intervention, B. cereus endophthalmitis typically results in loss of the eye within 48 hours. This outcome suggests that even if the infected eye is rendered sterile by antibiotics, ocular damage continues to occur, possibly due to toxin production by a uniquely virulent strain. This could be the case for any toxigenic infectious agent; however, because of the rapid and devastating nature of B. cereus endophthalmitis despite drastic therapeutic measures, understanding the relationship of toxin production to virulence is critical.
Cereolysin O is a thiol-activated cytolysin related to a group of oxygen-labile enzymes produced by several Gram-positive species, including streptolysin O of Group A streptococci, L. monocytogenes listeriolysin, and pneumolysin of S. pneumoniae. These enzymes have been implicated as virulence factors in experimental models of infection. Cereolysin O binds to cholesterol, a component of all mammalian cell membranes, as an initial step prior to cell lysis. Therefore, cells of the posterior segment of the eye are prone to damage. Cereolysin O is lethal in murine models of intravenous injection; however, whether cereolysin O contributes to fulminating B. cereus endophthalmitis is not known.
Cereolysin AB has been characterized as a cytolytic unit unrelated to cereolysin O. Cell lysis occurs via sequential action on membranes by independent activities of sphingomyelinase and phosphotidylcholine-phospholipase C. These components of cereolysin AB combine synergistically to lyse erythrocytes, but each can confer resistance to phagocytosis by neutrophils. Cereolysin AB has been proposed as an evolutionary precursor of Clostridium perfringens alpha-toxin, a noted virulence factor. Because of their membrane-specific activities, either cereolysin O or AB could damage or lyse retinal cells directly, or induce the production of inflammatory mediators which could contribute to tissue damage during infection.
Initial interest in B. cereus as a diarrheal-type food poisoning agent brought about the characterization of the vascular permeability factor as a potential cause. Recent characterization of this enterotoxic factor (also known as hemolysin BL) led to the implication of its involvement in B. cereus endophthalmitis. Hemolysin BL is a tripartite toxin, with hemolytic, dermonecrotic, and emetic activities, suggesting its potential to exert multiple toxic effects upon ocular tissues during fulminant endophthalmitis. Using an in vitro retinal button toxicity assay and in vivo vitreal injections of sterile supernatants and purified hemolysin BL, Beecher et al. suggested that B. cereus exotoxins, including hemolysin BL, can cause ocular damage during fulminant endophthalmitis. In these studies, however, hemolysin BL accounted for only half of the retinal toxicity of B. cereus supernatants, suggesting that full virulence is likely a multifactorial process.
A recent review suggested that B. cereus collagenase could be involved in ocular virulence. Collagenolytic enzymes can readily damage the vitreal and retinal architecture and have been reported to contribute to the virulence of Pseudomonas aeruginosa ocular infections. Collagen is a major constituent of the vitreous, supplying a potential target for this enzyme during endophthalmitis. Collagenolytic B. cereus strains have been isolated from cases of peridontitis and endophthalmitis, further suggesting that collagenase could contribute to virulence.
Other less well characterized B. cereus factors that could contribute to virulence include emetic toxin (cereulide), hemolysin II (murine lethal toxin), and phosphotidylinositol-phospholipase C (phosphatasemic factor). Emetic toxin (cereulide) has been reported to cause emesis in rhesus monkeys and vacuole formation in HEp-2 cells. Hemolysin II is a thermolabile toxin unrelated to cereolysin, that is lethal in simian models of intravenous administration. The phosphotidylinositol-phospholipase C has been shown to cause a phosphatasemia when injected intraveneously into rabbits. What contributions these proteins make, if any, to fulminant endophthalmitis have yet to be identified.