Characterization of the Pathogenesis of Experimental Gram–Negative Bacterial Endophthalmitis

Abstract

Abstract: : Purpose: The Gram–negative pathogens Escherichia coli and Klebsiella pneumoniae are common causes of endogenous endophthalmitis, a potentially blinding and sometimes bilateral infection of the posterior segment following spread from a distant infection site. The purpose of this study was to characterize the pathogenesis of endophthalmitis caused by these pathogens in new rabbit and murine experimental models of infection. Methods: Rabbits (New Zealand White) and mice (C57BL/6J) were injected intravitreally with approximately 2 log₁₀ cfu of ocular isolates of either E. coli or K. pneumoniae. Infections were analyzed every 3 hours for 15 hours by biomicroscopy, histology, bacterial and inflammatory cell quantification, and electroretinography. Results: E. coli and K. pneumoniae caused severe inflammation and rapid retinal function loss in infected eyes over an 15–hour time period. E. coli and K. pneumoniae grew logarithmically in the eye until approximately 9 hours postinfection. A stationary phase of growth was reached shortly thereafter at approximately 9 log₁₀ cfu/eye for each strain. Intraocular inflammation, including influx of inflammatory cells into the anterior chamber and cornea, reached moderate to severe levels by 9 to 12 hours postinfection. Eyes infected with each pathogen also exhibited rapid declines in retinal function. The b–wave amplitudes of eyes infected with E. coli or K. pneumoniae declined to approximately 40% or 55%, respectively, by 9 hours postinfection, and to <5% by 15 hours postinfection. Conclusions: Our findings demonstrate the explosive and sight–threatening consequences of endophthalmitis caused by E. coli and K. pneumoniae in models amenable to analysis of both the bacterium and host. Future studies are focused on analyzing the contribution of these pathogens and their virulence factors to vision loss during endophthalmitis, improved chemotherapy for endophthalmitis caused by these pathogens, and the role of immunocompromise in the evolution of Gram–negative endogenous endophthalmitis.

Keywords: endophthalmitis • bacterial disease • retina