Dallas—Moxifloxacin 0.5% (Vigamox, Alcon Laboratories) outperformed gatifloxacin 0.3% (Zymar, Allergan) in a comparative study of the penetration of fourth-generation fluoroquinolones with four-times-daily dosing into the aqueous humor in patients undergoing cataract surgery, according to James P. McCulley, MD.
Adequate penetration is important in cataract surgery, he explained, considering that none of the already available antibiotics provide good coverage against Streptococcus, resistant Staphylococcus, and Microbacterium, and the third-generation fluoroquinolones do not penetrate adequately into the aqueous humor with four-times-daily dosing. Another important consideration is the availability of a drug against which microorganisms would develop resistance slowly, he explained. Dr. McCulley is professor and chairman, department of ophthalmology, The University of Texas Southwestern Medical School, Dallas.
"The aqueous humor concentration of an antibiotic at the beginning of cataract surgery is relatively clinically irrelevant. On the other hand, it gives us a great surrogate for what we can accomplish with various dosing regimens," Dr. McCulley said.
The regimen he followed is four-times-a-day dosing 1 day preoperatively and one drop of antibiotic 1 hour before entering the anterior chamber. An aqueous sample then was obtained and then frozen by a technician and analyzed in Dr. McCulley's laboratory. All participants in the study were masked to the drug being administered.
He reported that moxifloxacin penetrated significantly more (p < 0.001) into the aqueous humor compared with gatifloxacin.
"Moxifloxacin penetrated to 1.86 μg/ml and gatifloxacin penetrated to 0.94 μg/ml," Dr. McCulley said.
When he and his colleagues compared these results with levofloxacin (Quixin, Santen Pharmaceuticals) and ciprofloxacin (Ciloxan, Alcon), both prior-generation antibiotics, the fourth-generation antibiotics penetrated significantly more than their pharmacologic predecessors.
Considering all this, Dr. McCulley posed the question: How much penetration is enough?
"A mutation-prevention concentration of an antibiotic will not encourage the development of mutations and resistance. We know that if we remain above a therapeutic level these are less likely to happen. However, really to prevent mutations, we will have to go higher. Based on the available microbiology and infectious disease literature, an ideal kill concentration is a concentration maximum (Cmax) that is 10 times the minimum inhibitory concentration (MIC) to assure killing the microorganisms," he stated.
Dr. McCulley underscored the importance of an adequate concentration by explaining that most of the sutureless temporal clear corneal incisions used in cataract surgery leak. This leakage probably is what accounts for the increased incidence of endophthalmitis after cataract surgery.
"The rate of endophthalmitis has increased to about 1 in 400 cases with sutureless incisions compared with fewer than 1 in 1,000 cases previously. In our center, where we ensure a water-tight wound, commonly using one suture for temporal clear corneal incisions, we had one case of endophthalmitis develop in 12,000 cases. In my opinion, we should be able to eradicate endophthalmitis after cataract surgery with good surgical techniques and good prophylaxis," he emphasized.
So, how much is enough?