Effects of intravitreal dexamethasone on concentration of intravitreal vancomycin in experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis

Abstract

Intravitreal corticosteroids in the treatment of bacterial endophthalmitis remain controversial. We utilized an experimental rabbit model of methicillin-resistant Staphylococcus epidermidis endophthalmitis (i) to calculate the intravitreal vancomycin concentration in rabbit eyes receiving intravitreal vancomycin alone or in combination with intravitreal dexamethasone and (ii) to determine whether an intravitreal steroid has any effect on intravitreal vancomycin levels. All right eyes were infected and all left eyes were uninfected. The rabbits were divided into two treatment groups: (i) 32 eyes (group I) were injected with intravitreal vancomycin, 1.0 mg (0.1 ml); (ii) 32 additional eyes (group II) were injected with intravitreal dexamethasone, 400 ,ug (0.1 ml), in addition to vancomycin. Measurement of intravitreal vancomycin concentration was performed following sacrifice, utilizing a microbiologic agar diffusion assay. Analyses of intravitreal vancomycin concentrations were performed by using model-independent parameters, with area under the concentration-time curves derived by trapezoidal approximation. The intravitreal vancomycin concentration was significantly lower in both uninfected and infected group II eyes (P < 0.002). Analysis of intravitreal vancomycin concentration-time relationships was performed by using a nonlinear least-squares regression program; data best fit a one-compartment model. In addition, no vancomycin-dexamethasone interaction could be demonstrated. The reduced level of intravitreal vancomycin in the presence of intravitreal dexamethasone may have important clinical implications.

Effect of intravitreal dexamethasone on vitreous vancomycin concentrations in patients with suspected postoperative bacterial endophthalmitis

“…Also in ophthalmology, corticosteroids have a beneficial effect on the outcome of endophthalmitis in most animal studies ( [5], [7]). However, two studies ( [8], [10]) reported that dexamethasone may decrease the vancomycin concentrations, a possible concern for their combined use.…”

An in vitro study on the compatibility and concentrations of combinations of vancomycin, amikacin, and dexamethasone in human vitreous

“…However, animal experimental models with Streptococcus pneumoniae and Staphylococcus epidermidis had yielded conflicting results. 19,20 As our in vitro study suggests that loss of vancomycin was minimal, either alone or in the presence of other medications or media, other in vivo variations, such as organism characteristics, host inflammatory response and breakdown of blood-ocular barrier, may account for the opposite results obtained by previous in vivo studies. Smith et al 19 had suggested that the elimination of vancomycin through the canal of Schlemm may be facilitated by the presence of steroids, resulting in lower intraocular levels.…”

Effect of caffeic acid phenethyl ester on treatment of experimentally induced methicillin‐resi̇stant Staphylococcus epidermidis endophthalmitis in a rabbit model

“…They were also able to demonstrate that early treatment with vancomycin not only eradicated the infection (confirmed microbiologically) but also preserved the retinal architecture (shown histopathologically). In another study, it was reported that in experimental MRSE endophthalmitis when intravitreal dexamethasone was included in the treatment, less intravitreal vancomycin concentration was needed 35 because of this, therapy with a single dose of intravitreal vancomycin together with dexamethasone may be sufficient to treat endophthalmitis with a low-virulence organism such as MRSE.…”