Evaluation of therapeutic measures for treating endophthalmitis caused by isogenic toxin-producing and toxin-nonproducing Enterococcus faecalis strains.
OBJECTIVE
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.
Jett
B D
BD
Division of Laboratory Medicine, Washington University School of Medicine, St. Louis Missouri.
Jensen
H G
HG
Atkuri
R V
RV
Gilmore
M S
MS
D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003907:Dexamethasone / Q000627:therapeutic use*; D004596:Electroretinography; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology*; D013293:Enterococcus faecalis / Q000378:metabolism; D015818:Eye Infections, Bacterial / Q000188:drug therapy*; D005839:Gentamicins / Q000627:therapeutic use*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D011817:Rabbits; D014822:Vitreous Body
D001427:Bacterial Toxins; D005839:Gentamicins; D000667:Ampicillin; D003907:Dexamethasone