Intravitreal vancomycin may boost postop protection

Vitreous vancomycin concentrations for the treatment of gram-positive endophthalmitis were therapeutic after intravitreal administration, study shows.

ByRochelle Nataloni

TEL AVIV, Israel — A single dose of intravenous vancomycin in eyes with gram-positive endophthalmitis results in erratic penetration, according to a study out of the Department of Ophthalmology at Meir Hospital, Sapir Medical Center and the Department of Infectious Diseases, Sheba Medical Center here. According to lead investigator, Joseph R. Ferencz, MD, this confirms that intravenous therapy with vancomycin cannot be relied on as a sole mode of therapy in patients with postoperative endophthalmitis.

“Penetration of intravenous vancomycin into the vitreous cavity after intravenous administration is thought to be limited and variable, based in part on the severity of intraocular inflammation and resultant breakdown of the blood ocular barriers,” according to Dr. Ferencz, who published his findings and observations in Archives of Ophthalmology (1999;117: 1023-1027). “Routine use of intravenous antibiotic drugs that were previously a mainstay of therapy has come into question as a result of findings of the Endophthalmitis Vitrectomy Study, which showed no benefit,” he said.

An intravitreal edge

The study measured vancomycin concentrations in the vitreous after its intravenous and intravitreal administration, and determined whether such concentrations are adequate for the treatment of representative organisms that cause gram-positive endophthalmitis in humans. Dr. Ferencz concluded that vitreous vancomycin concentrations for the treatment of gram-positive endophthalmitis were non-therapeutic after intravenous ad-ministration, but therapeutic after intravitreal administration.

Patients with acute postoperative endophthalmitis were treated with intravenous administration of 1 g of vancomycin hydrochloride followed by vitrectomy and collection of vitreous samples 1 to 5 hours later. Intravitreal vancomycin and ceftazidime were given. Vitreous samples were cultured and their vancomycin concentrations were assayed. Minimal inhibitory concentrations (MICs) of vancomycin for the isolated vitreal pathogens and serum and vitreous cidal activity values were determined.

Eighteen patients with acute postoperative endophthalmitis were studied. Fourteen vitreous samples were available after intravenous vancomycin administration, and four vitreous samples were available after intravitreal vancomycin administration. After intravenous injection, vitreous vancomycin concentrations ranged from 0.4 to 4.5 µg/mL. MICs in these samples, obtained from 10 bacterial isolates, were below therapeutic levels for most causative organisms, including staphylococci. Vitreous cidal activity values were negative at a dilution of 1:2 in nine of 10 patients examined. After a 1 mg intravitreal injection, vancomycin concentrations in vitreous samples obtained by a second tap from four patients 44 to 72 hours later were 182, 138, 58 and 25 µg/mL. In two patients in whom measurements were obtained, vitreous cidal activity values were 1:512 and 1:32.

Patients and methods

Of the patients participating in the study, cataract surgery had been performed in one of seven surgical centers, including Sapir Medical Center. Immediately after confirmation of the diagnosis, all patients except one were administered 1 g of vancomycin hydro-chloride intravenously for 20 minutes. One to 5 hours later, each patient who received vancomycin was taken to the operating room. An anterior chamber maintainer was inserted and vitreous tap was performed through a pars plana sclerotomy using a vitrectomy probe. A 1 mL tuberculin syringe was connected to the suction tube, and vitreous material was drawn into the syringe from the dead space of the tubing. Balanced salt solution was injected through the anterior chamber maintainer only after vitreous biopsy, and either core or complete vitrectomy was performed.

Vancomycin hydrochloride, 1 mg in 0.1 mL of saline solution, and ceftazidime, 2.25 mg in 0.1 mL of saline solution, were then injected into the vitreous cavity.

The vitreous specimens were submitted for microbiologic cultures and determination of vancomycin concentrations. Bacterial isolates were identified according to conventional micro- biologic techniques, and the MIC of vancomycin for each isolate was determined.

Dr. Ferencz determined that the vitreous levels were not delayed for more than 5 hours after administration of the drug because it was considered unethical to place the patient at risk by delaying surgery. In four patients, it became necessary to perform a second vitrectomy and intravitreal injection. As such, intravitreal vancomycin levels could be measured 2 to 3 days after a single injection. Vitreal vancomycin levels in these patients were up to 100 times higher than after intravenous injection alone, and the vitreous cidal activity was present at dilutions of between 1:32 and 1:514.

According to Dr. Ferencz and colleagues, the study indicates that administration of a single intravitreal vancomycin dose maintains high and effective vitreous levels for at least 3 days, and therefore in postoperative endophthalmitis caused by gram-positive cocci, the administration of intravenous vancomycin administration is probably not indicated.

For Your Information:

Joseph R. Ferencz, MD, can be reached at 4 Kalisher St., Kfar Saba, 44380, Israel; phone and fax: +(972) 9-766-0543. Dr. Ferencz has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.