Aminoglycoside levels in the rabbit vitreous cavity after intravenous administration.

PURPOSE: To determine the penetration of gentamicin and amikacin into the rabbit vitreous cavity after their intravenous administration. METHODS: Gentamicin (1.6 mg/kg every 8 hours) and amikacin (6 mg/kg every 12 hours) were administered intravenously to 25 rabbits that had previously had the lens and vitreous removed from 43 eyes. For each drug, ocular inflammation was induced in one group of eyes by injection of heat-killed Staphylococcus epidermidis, while the other group was maintained as a control. Samples from the vitreous cavity were taken at regular intervals for 72 hours after beginning the intravenous medications and were analyzed for drug concentrations. RESULTS: The maximum intravitreal concentration +/- SD achieved for gentamicin was 1.8 +/- 0.5 microgram/ml. The maximum intravitreal concentration for amikacin was 8.5 +/- 3.2 micrograms/ml. Inflamed eyes demonstrated higher concentrations than did those without inflammation. CONCLUSIONS: In a rabbit model with conditions optimized to enhance penetration of antimicrobials into the vitreous cavity after intravenous administration, neither gentamicin nor amikacin penetrated sufficiently to reach potentially therapeutic concentrations consistently for either Pseudomonas or S epidermidis organisms.

Comparative treatment of experimental Staphylococcus aureus endophthalmitis.

PURPOSE: To compare treatment strategies for Staphylococcus aureus endophthalmitis, we created an animal model in an aphakic rabbit eye and tested six different approaches to treatment. METHODS: Rabbit eyes were rendered aphakic, and three weeks postoperatively, S. aureus organisms were injected into the vitreous cavity. One group was maintained as a control. Twenty-four hours after bacterial injection, six different treatment groups were created for comparison. Clinical inflammation scores, culture results 48 hours after treatment, histopathologic gradings, and development of total corneal opacity three weeks after treatment were assessed. RESULTS: Injection of vancomycin hydrochloride into the vitreous cavity was more effective than injection of cefazolin sodium (P = .01) in reducing the percentage of eyes that had positive culture results and also resulted in lower inflammation scores. Vitrectomy plus injection of either antibiotic was more effective than injection of the same antibiotic alone in reducing culture-positive results and reducing clinical inflammation scores. addition of systemic corticosteroids to intravitreal antibiotic injection did not improve any measure of outcome. Vitrectomy and injection of intravitreal vancomycin was the most effective strategy to sterilize the vitreous cavity, resulting in the lowest inflammation scores and the smallest percentage of eyes with opaque corneas. CONCLUSION: In an animal model of S. aureus endophthalmitis, the combination of vitrectomy and injection of intraocular vancomycin was the most effective strategy for rapidly controlling the infective process and improving the outcomes measured three weeks after treatment.

Intraocular dexamethasone produces a harmful effect on treatment of experimental Staphylococcus aureus endophthalmitis.

BACKGROUND: We created a standardized model of severe Staphylococcus aureus endophthalmitis in the aphakic rabbit eye to test various treatment strategies involving corticosteroid administration in addition to vitrectomy and antibiotic treatment. MATERIALS AND METHODS: In 71 aphakic New Zealand albino rabbit eyes, experimental endophthalmitis was created by injecting 10(5) colony-forming units of Staphylococcal aureus. The animals were divided into 5 groups. One control group was followed up without treatment, while 4 groups were treated with vitrectomy and intraocular cefazolin injection. Two groups were also treated with intramuscular methylprednisolone, 1 group beginning on the day of surgery and 1 group beginning on the following day. In the final group, dexamethasone, 400 micrograms, was injected into the vitreous cavity at the close of surgery. Culture results were compared on the first 2 days after surgery. Inflammatory scores, including development of total corneal opacity, were assessed over a 21-day follow-up period, and histopathologic grading was carried out at the conclusion of the clinical observations. RESULTS: Simultaneous administration of systemic corticosteroids beginning on the day of vitrectomy decreased inflammatory scores 1 week after institution of therapy but did not affect final scores. Delay of initiation of intramuscular corticosteroid until the first postoperative day negated the positive effects. Administration of intraocular corticosteroids was associated with an increase in inflammatory scores throughout the period of observation, an increase in percentage of eyes that developed opaque corneas, an increase in choroidal inflammation graded moderate or severe, and an increase in retinal necrosis compared with vitrectomy and cefazolin injection alone. CONCLUSIONS: This data suggest caution in the use of intraocular corticosteroids in treatment of severe endophthalmitis.

Vancomycin levels in the vitreous cavity after intravenous administration.

PURPOSE: We studied the effects of inflammation, repeated antibiotic doses, and the surgical status of the eye on penetration of vancomycin hydrochloride into the rabbit vitreous cavity after intravenous administration. METHODS: We studied three anatomic states (phakic, aphakic, and aphakic, vitrectomy-treated eyes) subdividing each into inflamed and noninflamed groups. Intravenous vancomycin hydrochloride (15 mg/kg of body weight) was administered every 12 hours for 48 hours. Eyes were harvested for the assay of vitreous cavity antibiotic levels at various intervals from one to 49 hours. We determined concentrations and calculated mean values and S.E.M. RESULTS: Therapeutic levels were not established in the vitreous cavity at any time period in the two phakic groups. At 25 hours, the inflamed aphakic eyes had concentrations of 5.05 +/- 1.9 micrograms/ml and the control noninflamed aphakic eyes 4.5 +/- 1.23 micrograms/ml; slight increases were found by 49 hours. Concentrations tested in the aphakic, vitrectomy-treated eyes at two, 13, 25, and 49 hours demonstrated progressive increases both in the inflamed eyes (5.4 +/- 2.4 micrograms/ml, 9.64 +/- 4.25 micrograms/ml, 9.2 +/- 3.96 micrograms/ml, 10.34 +/- 4.49 micrograms/ml) and noninflamed eyes (3.52 +/- 2.1 micrograms/ml, 5.4 +/- 1.96 micrograms/ml, 6.8 +/- 2.53 micrograms/ml, 8.7 +/- 5.44 micrograms/ml). CONCLUSIONS: Vitreous vancomycin concentrations in aphakic and aphakic, vitrectomy-treated eyes after intravenous administration exceed the minimal inhibitory concentrations for the usual gram-positive pathogens that create endophthalmitis, suggesting a role for intravenous vancomycin in the treatment of bacterial endophthalmitis.

Vitreous cavity penetration of ceftazidime after intravenous administration.

PURPOSE: Penetration of ceftazidime, a third generation cephalosporin, into the vitreous cavity after intravenous administration was investigated. METHODS: Because antimicrobial penetration varies with surgical status of the eye and with inflammation, studies were conducted in phakic, aphakic, and aphakic, vitrectomized eyes in both normal and inflamed conditions. Ceftazidime 50 mg/kg was administered every 8 hours and vitreous cavity concentrations were tested at intervals from 2 to 72 hours after the initial dose. RESULTS: No penetration was found into control phakic and aphakic eyes, but drug concentrations were detected in inflamed eyes at 24 hours. Vitreous concentrations of ceftazidime in aphakic, vitrectomized eyes reached levels well above the minimal inhibitory concentration (MIC) for Pseudomonas organisms within 2 hours of intravenous administration in control eyes (8.5 micrograms/ml) and inflamed eyes (35.4 micrograms/ml). Inflammation and removal of the lens and vitreous significantly enhanced ceftazidime penetration at all time periods tested. CONCLUSION: Ceftazidime penetrates into the vitreous cavity of inflamed eyes after intravenous administration and achieves concentrations above the MIC for Pseudomonas organisms. Penetration is greatest in aphakic, vitrectomized eyes.

Vancomycin levels after intravitreal injection. Effects of inflammation and surgery.

OBJECTIVE: Vancomycin hydrochloride for intraocular injection is the drug of choice for the treatment of suspected gram-positive endophthalmitis. To study its intraocular pharmacokinetics, we injected vancomycin into the vitreous cavity of phakic, aphakic, and aphakic-vitrectomized rabbit eyes and determined its rate of clearance. Inflamed eyes were compared to control eyes in each group. METHODS: Three groups of eyes were prepared. The eyes in Group 1 were phakic, the eyes in Group 2 had the lens removed, and the eyes in Group 3 had both the lens and central vitreous removed. Each group was subdivided into a control group and a group made inflamed by injection of heat-killed Staphylococcus epidermidis. Vancomycin hydrochloride 1 mg in 0.1 cc of diluent was injected into the midvitreous cavity and samples obtained at 2 or 3, 8, 24, and 48 hours after injection. Vancomycin concentrations were measured and clearance rates were calculated for each of the groups. RESULTS: Vancomycin was cleared substantially faster from aphakic-vitrectomized eyes (half-life 9.0 hours) and aphakic eyes (half-life 8.9 hours) than phakic eyes (half-life 25.1 hours). Inflammation increased the rate of elimination of vancomycin only in the aphakic group. CONCLUSIONS: Clearance of vancomycin from the phakic eye is prolonged compared to that of beta-lactam antibiotics, an important pharmacokinetic advantage in treating endophthalmitis. Its clearance from aphakic-vitrectomized eyes is dramatically faster than from phakic eyes and is similar to that of other antimicrobial agents.

Antibacterial effects of previously infected or inflamed vitreous.

The authors investigated the ability of vitreous harvested from eyes previously infected with Staphylococcus epidermidis or inflamed with heat-killed cells of the same organism to support subsequent in vitro bacterial growth. Growth of S. epidermidis and S. aureus was not supported by previously inflamed or previously infected vitreous, but Pseudomonas aerugnosa grew in all samples. These findings suggest induction of an antistaphylococcal substance by infection or inflammation of rabbit vitreous by S. epidermidis.

Complications of tissue plasminogen activator therapy after vitrectomy for diabetes.

Human recombinant tissue plasminogen activator (25 micrograms) was injected into seven eyes of six patients who had developed massive fibrin deposition after vitrectomy surgery for diabetes. Six eyes had developed pupillary membranes and recurrence of tractional retinal detachment from fibrin membranes, and one eye had developed only a pupillary membrane. All pupillary membranes resolved within one hour of administration of tissue plasminogen activator, and five tractional retinal detachments resolved within 24 hours. All eyes developed evidence of intraocular bleeding after tissue plasminogen activator injection. Subsequently, six of seven eyes developed recurrence of fibrin accumulation and tractional retinal detachment.

Comparative treatment of experimental Staphylococcus epidermidis endophthalmitis.

We created experimental Staphylococcus epidermidis endophthalmitis of moderate severity in the aphakic rabbit eye by injecting 100,000 organisms of a standardized laboratory strain (ATCC 155) into the mid-vitreous cavity. This model of endophthalmitis self-sterilizes in about 4 days, but inflammatory signs continue to increase 5 to 7 days after the initial bacterial inoculum. Control eyes were compared with eyes treated with five different strategies 24 hours after bacterial inoculation: intravitreal cefazolin sodium, intravitreal cefazolin plus intramuscular corticosteroid, vitrectomy plus intravitreal antibiotics, vitrectomy plus intravitreal antibiotics and intramuscular corticosteroids, and vitrectomy plus intravitreal antibiotics and corticosteroids. Quantitative grading of inflammation and media clarity were compared at the end of weeks 1, 2, and 3 after treatment. At week 1, eyes treated with vitrectomy had significantly lower inflammatory scores; those treated with corticosteroids had significantly lower scores than those without. The two effects were independent. The best results were observed with treatment consisting of vitrectomy, intraocular antibiotics, and corticosteroids. This strategy also produced significantly more eyes with clear media at the end of week 3 than treatment with intravitreal antibiotics alone.

The effect of tissue plasminogen activator on retinal bleeding.

Tissue plasminogen activator is a potent thrombolytic agent that recently has been used to treat postvitrectomy fibrin formation. However, a recent report noted anterior and posterior segment bleeding following intracameral tissue plasminogen activator injection. In this study, we performed lensectomy and vitrectomy in 20 rabbits. A retinal blood vessel was incised to stimulate intraocular hemorrhage; bleeding was controlled and vitreous hemorrhage aspirated. Postoperatively, one eye received a 0.1-mL injection of tissue plasminogen activator (25 micrograms); the other received balanced salt solution. The eyes receiving tissue plasminogen activator had a 28% incidence of increased anterior chamber blood and a 61% incidence of increased intravitreal blood. There was no evidence of postinjection bleeding in eyes receiving balanced salt solution. Most cases of bleeding occurred within 24 hours of tissue plasminogen activator injection. Administration of tissue plasminogen activator in the setting of segmented blood vessels may lead to intraocular hemorrhage.