Antibiotic-soaked IOLs show efficacy against bacteria

Hydrophilic acrylic lens immersed for 24 hours in antibiotic solution have been shown more effective than current treatments in study.

ByMichela Cimberle

IOLs as a drug-delivery system for antibiotics, used alone or in association with topical and intracameral delivery, may be an effective alternative against the increasingly resistant bacteria that cause endophthalmitis, according to one surgeon.

“Resistance to antibiotics is an emerging reality, an increasing concern and a widely debated issue in ocular surgery,” Randall J. Olson, MD, said.

About 8 years ago, latest- generation fluoroquinolones, the “new weapons in the arsenal of ophthalmic antibiotics,” were hailed as a solution to resistant bacteria.

Organisms that were resistant to ciprofloxacin, ofloxacin and levofloxacin were easily defeated by gatifloxacin and moxifloxacin, according to Dr. Olson.

“Fourth-generation fluoroquinolones were indeed a dramatic improvement, and we were confident that they would always be available to us,” he said.

However, in November 2006, an article by Deramo and colleagues pointed out that several species of staphylococci were rapidly developing resistance to the latest-generation fluoroquinolones.

“The majority of the organisms at the origin of bacterial endophthalmitis were already resistant, and resistance was already up to the 6 mcg/mL to 8 mcg/mL level, which you can achieve with any topical application,” Dr. Olson said. “So it turned out that topical prophylaxis was going to be an increasing problem.”

Alternative methods

Collagen shields that were developed as a possibly more effective system of delivering the drug failed to meet expectations. The concentration of gatifloxacin and moxifloxacin were 2.3 mcg/mL and 3 mcg/mL, respectively, at 3 hours and 0.76 mcg/mL vs. 0.29 mcg/mL at 6 hours.

“Gatifloxacin appeared to be better in this particular case. It could also be supplemented with the topical approach, but there was no way it could fight resistance to the 6 mcg/mL to 8 mcg/mL level,” Dr. Olson said.

The intracameral approach, evaluated in a large series of patients by the ESCRS endophthalmitis study, has proved to be an effective prophylactic method and is rapidly gaining popularity. However, issues have been raised by the off-label use of cefuroxime, and resistance to the drug may increase over time. In addition, because the average term of the aqueous in the eye is 20 to 30 minutes, intracameral-delivered antibiotics have a short half-life and do not provide long-term coverage.

The use of an IOL as a reservoir and alternative delivery system for antibiotics was first published by Kleinmann and colleagues in 2006.

The lens used was a Centerflex (Rayner) hydrophilic acrylic, soaked for 24 hours in commercial topical preparation of 0.3% gatifloxacin or 0.5% moxifloxacin. Antibiotic levels, measured by liquid chromatography, were compared with those of topical antibiotics administered every 5 minutes three times preoperatively and 2 hours postoperatively in rabbits.

Long half-life, prolonged efficacy

“There were no signs of toxicity with either method,” Dr. Olson said. “The levels in association with the topical approach were exactly as expected — roughly 2 mcg/mL for the moxifloxacin and 1.25 mcg/mL for the gatifloxacin, which is essentially the same ratio of the two antibiotics in solution.”

With the antibiotic-soaked IOL, antibiotic levels at 4 hours were more than 12 mcg/mL with gatifloxacin and about 10 mcg/mL with moxifloxacin.

“These are very high levels, which would be indeed effective on the moderately resistant bacteria that are becoming a problem now,” Dr. Olson said.

Effective levels were still present at 8 hours, with 8 mcg/mL for gatifloxacin and 4.5 mcg/mL for moxifloxacin. At 12 hours, gatifloxacin concentration was 4 mcg/mL and moxifloxacin was 2.6 mcg/mL.

“It’s interesting to note that this was opposite to the concentration of topical preparations in solution (0.3% gatifloxacin vs. 0.5% moxifloxacin). Obviously this was something to do with the binding and release inside the material of the lens and was similar to the effect produced by collagen shields,” he said.

Gatifloxacin concentration was higher from IOL delivery at all three time points, and the difference with topical administration was statistically significant. For moxifloxacin, the concentration was significantly higher from IOL delivery at 4 and 8 hours.

“IOLs soaked with antibiotics guarantee high levels for 8 to 12 hours,” Dr. Olson said. “The beauty of this approach is that the half-life of the drug, rather than being 20 to 30 minutes, is 4 hours because we have a reservoir that makes the antibiotic last for a much longer period of time.”

Aggressive approach

According to Dr. Olson, this approach can benefit from supplementation with topical or intracameral antibiotics.

“It is clear that with these emerging resistant organisms, multiple approaches may be beneficial and supplement each other,” he noted.

Intracameral injection, for instance, would provide the benefit of an early spike, which would be prolonged in the long-term effect and longer half-life of the IOL delivery.

Future efforts could be directed toward finding the best IOL material for a better antibiotic concentration, trying different antibiotics for the best effect and defining the length of time the IOL needs to be soaked for best performance, Dr. Olson said.

“Potentially, we could even develop an IOL that is pre-soaked at higher antibiotic levels and create an IOL that releases the antibiotic more slowly for a more prolonged effect,” he said. “This is just the beginning of a series of experiments.

“I am afraid that in our ongoing battle with bacteria, in which the bacteria seem to be winning the battle, an aggressive approach is mandatory, and such innovative methods may become increasingly important in the future,” he said.

For more information:

Randall J. Olson, MD, can be reached at John Moran Eye Center, 50 N. Medical Drive, Salt Lake City, UT 84132 U.S.A.; +1-801-585-6622; fax: +1-801-581-8703; e-mail: randall.olson@hsc.utah.edu. Dr. Olson has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.

References:

Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol, 2002;133:463-466.

Deramo VA, Lai JC, Fastenberg DM, Udell IJ. Acute endophthalmitis in eyes treated prophylactically with gatifloxacin and moxifloxacin. Am J Ophthalmol. 2006;142:721-725.

Kleinmann G, Apple DJ, et al. Hydrophilic acrylic intraocular lens as a drug-delivery system for fourth-generation fluoroquinolones. J Cataract Refract Surg. 2006; 32:1717-1721.

Michela Cimberle is an OSN Correspondent based in Treviso, Italy, who covers all aspects of ophthalmology. She focuses geographically on Europe.