Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: host-microbe interactions in intraocular infection

Abstract

Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular degeneration raises yet additional risks. Compounding the problem is the continuing progression of antibiotic resistance. Visual prognosis for endophthalmitis depends on the virulence of the causative organism, the severity of intraocular inflammation, and the timeliness of effective therapy. We review the current understanding of the pathogenesis of bacterial endophthalmitis, highlighting opportunities for the development of improved therapeutics and preventive strategies.

Figure 1

Peptide-based quorum sensing in gram positive bacteria. A precursor peptide co-secretionally processed into mature form by an ABC transporter. The peptide accumulates outside the cell as function of bacterial cell density. A threshold level detected by the cognate sensor histidine protein kinase transduces the signal to a response regulator through phosphotransfer. This leads to a shift in global regulation of virulence gene expression. Competence-stimulating peptide (CSP); gelatinase biosynthesis-activating pheromone (GBAP); auto inducing peptide (AIP).

Figure 2

Course of rabbit endophthalmitis as a function of treatment regimen, as measured by % ERG B-wave amplitude retention (b-wave in infected eye/b-wave in control eye ×100). Antibiotic therapy consisting of ampicillin (1 mg/0.1 ml) and gentamicin (200 ug/0.1 ml) for endophthalmitis from either cytolytic (in green) or non-cytolytic (in purple) E. faecalis provides little improvement over untreated controls. Inclusion of dexamethasone (400 ug/0.1 ml) results in complete recovery of retinal function in eyes infected with non-cytolytic E. faecalis, but provides no measurable benefit for eyes infected with the cytolytic E. faecalis.

Figure 3

The peptide subunits CylL_L and CylL_S are ribosomally synthesized in the cell. Following post-translational modification by CylM, they are cleaved and secreted to be activated extracellularly by CylA. This allows the fully active peptides to act together to lyse prokaryotic and eukaryotic cells, in addition to inducing expression of the cytolysin operon. CylR1 and CylR2 serve to repress expression of the operon. The cytolysin-producing cell itself is protected by CylI.