Oral moxifloxacin might be adjunct in endophthalmitis

November 15, 2005

Montr?al—Oral moxifloxacin (Avelox, Bayer) can penetrate into the vitreous at a level that can kill most common pathogens in the eye. This drug, a fluoroquinolone, may play a role in the treatment or prevention of endophthalmitis.

However, the vitreous concentration of moxifloxacin may be ineffective against resistant Staphylococcus strains, reported Jeffrey J. Fuller, MD, at the American Society of Retina Specialists meeting in Montréal.

The Endophthalmitis Vitrectomy Study (EVS) shed some light on the nature of the organisms that cause endophthalmitis and the few drugs used to attempt treatment, which were not effective.

The study investigators concluded that intravenous administration of antibiotics is ineffective in these cases. However, Dr. Fuller pointed out that only ceftazidime and amikacin, which have relatively poor intraocular penetration, were administered systemically. Fluoroquinolones were not used routinely in the study.

"Moxifloxacin is the newest FDA-approved systemic and topical fourth-generation fluoroquinolone," explained Dr. Fuller, a retina fellow, department of ophthalmology and visual science, University of Iowa, Iowa City.

"The purported selling point of the fourth-generation fluoroquinolones is that they inhibit both topoisomerase II (DNA gyrase) and topoisomerase IV," Dr. Fuller said. "Gram-positive organisms use both of these enzymes in their DNA replication cycle, which indicates that two separate mutations may be required for resistance in these gram-positive species."

A recent report (Mather et al. Am J Ophthalmol 2002;133:463-466) on bacterial endophthalmitis isolates showed the results of testing different fluoroquinolones against the various organisms. The results showed that the fourth-generation fluoroquinolones generally fared better against the organisms and that of all the isolates tested, only 12 were resistant to moxifloxacin and 17 were resistant to gatifloxacin. The minimum inhibitory concentrations against the different strains were generally lower for moxifloxacin than other fluoroquinolones tested.

In light of this, Dr. Fuller and colleagues conducted a prospective, nonrandomized study of 11 patients scheduled for vitrectomy. Three of the patients served as controls and received no medication. The eight other patients received one moxifloxacin pill (400 mg) the night before the surgery and another pill the morning of the surgery. Vitreous samples were obtained at the start of vitrectomy before the infusion began. Quantitative assays were performed using high-performance liquid chromatography.

Detectable levels of drug

"The mean concentration of moxifloxacin in the vitreous of patients receiving oral moxifloxacin was 1.55 µg/ml, with no detectable levels in the controls," Dr. Fuller explained.

"Oral moxifloxacin achieved substantial intravitreal penetration. This study is the first report of the penetration of oral moxifloxacin into the vitreous," Dr. Fuller said. "The potential impact of these findings is that moxifloxacin's favorable antimicrobial spectrum combined its high level of intravitreal penetration may make it the systemic drug of choice in the treatment and/or prophylaxis of endophthalmitis."