Penetration, potency, biocompatibility important in selecting an anti-infective

These attributes minimize the risk of complications and ensure the best surgical outcomes.

Issue: May 15, 2006

ByRichard L. Lindstrom, MD

The rate of infection after cataract or refractive surgery is low, but this complication can be devastating. Therefore, it is critical that we take every preventive measure possible to ensure that we protect our patients against potential infection. A major component to preventing infection is topical antibiotic therapy pre-, peri- and postoperatively.

Three important attributes should be considered when evaluating antibiotic drops: drug penetration, potency and biocompatibility.

Penetration and potency

Richard L. Lindstrom

Because infections can occur inside the eye, it is important for an antibiotic not only to provide therapeutic levels on the surface but also in the target tissues, such as the cornea and aqueous humor.

A controlled, randomized, multicenter study found that Vigamox (moxifloxacin HCl ophthalmic solution 0.5%, Alcon) has superior corneal penetration compared with Zymar (gatifloxacin ophthalmic solution 0.3%, Allergan). The study included 48 patients who were undergoing penetrating keratoplasty. Their corneas were analyzed after administration of either moxifloxacin or gatifloxacin.

The study found that peak stroma levels of moxifloxacin were three times higher than those of gatifloxacin. Additionally, the peak levels of moxifloxacin in the epithelium were seven times higher than those of gatifloxacin.

An anti-infective drug must also be potent at the potential site of infection. Exceeding the minimum inhibitory concentrations of pathogens that could cause infection after a drug has penetrated into the target tissue is the true measure of a drug’s effectiveness.

The newer generation of fluoroqui-nolones offers the best potency and penetration profile, and numerous clinical studies have confirmed that moxifloxacin provides superior potency and therapeutic penetration.

A study conducted at the Wilmer Eye Institute at Johns Hopkins University found that moxifloxacin achieved a statistically significantly higher concentration in the aqueous humor compared with gatifloxacin.

This study included 50 cataract patients; 25 were given perioperative topical moxifloxacin and 25 were given topical gatifloxacin. Moxifloxacin achieved a 3.8 times higher aqueous concentration than gatifloxacin. Moxifloxacin penetrated into the aqueous at concentrations that met or exceeded the infectious agent’s mutant prevention concentration for the most common endophthalmitis-causing susceptible pathogens. Gatifloxacin did not. In addition, moxifloxacin levels exceeded the minimum inhibitory concentrations for fluoroquinolone-resistant Staphylococcus aureus, whereas gatifloxacin levels did not.

Moxifloxacin’s superior penetration and antimicrobial activity provide enhanced prophylaxis against endophthalmitis and keratitis pathogens.

A separate disc diffusion analysis conducted using the aqueous humor levels achieved in the Wilmer Eye study found that the aqueous humor levels achieved for moxifloxacin demonstrated activity against S. aureus, creating a 24-mm zone of inhibition, whereas the aqueous humor levels achieved by gatifloxacin did not show any activity against S. aureus. This is an excellent model for defining protection by evaluating antibiotic efficacy at the potential site of infection.

Biocompatibility

We prefer to use a drug that offers no toxicity or impediment of wound healing.

An independent study conducted at the Center for Refractive Surgery in Washington concluded that both gatifloxacin and moxifloxacin were safe when used after PRK. However, eyes treated with moxifloxacin in the study showed faster healing and smaller epithelial defects than those treated with gatifloxacin.

This study included 35 patients who received gatifloxacin in one eye and moxifloxacin in the other eye after bilateral PRK with a 9-mm epithelial defect. Both eyes healed on the same day in 18 of the 35 patients. In 13 patients, the moxifloxacin-treated eye healed first, and in four patients, the gatifloxacin-treated eye healed first. The moxifloxacin-treated eyes healed in 3 to 7 days, while the gatifloxacin-treated eyes healed in 3 to 9 days.

Moxifloxacin delivers superior potency, therapeutic penetration and a favorable biocompatibility profile. This is important to me because it minimizes potential complications and ensures the best surgical outcomes.

For more information:

Richard L. Lindstrom, MD, is the Chief Medical Editor of Ocular Surgery News. He is a clinical professor of ophthalmology at the University of Minnesota and in private practice at Minnesota Eye Consultants, 710 E. 24th St., Suite 106, Minneapolis, MN 55404; 612-813-3600; fax: 612-813-3660. Dr. Lindstrom is a paid consultant for Alcon.

Alcon Inc., maker of Vigamox, can be reached at 6201 South Freeway, Fort Worth, TX 76134; 817-293-0450; fax: 817-568-6142; Web site: www.alconlabs.com.

References:

Burka JM, Bower KS, et al. The effect of fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on epithelial healing following photorefractive keratectomy. Am J Ophthalmol. 2005;140(1):83-87.

Kim DH, Stark WJ, et al. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology. 2005;112:1992-1996.

Kim DH, Stark WJ, et al. Ocular penetration of moxifloxacin 0.5% and gatfloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery. Curr Med Res Opin. 2005;21(1);93-94.

Kim T, Lane S, et al. Human corneal stroma and epithelium concentrations of moxifloxacin and gatifloxacin following topical ocular dosing with Vigamox and Zymar. Presented at: Ocular Microbiology and Immunology Group meeting, October 15, 2005, Chicago.

Mather R, Karenchak LM, et al. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002:133(4):463-466.

O’Brien TP, Stroman DW. A comparison of ocular penetration and microbiological efficacy of fourth generation fluoroquinolones in cataract surgery patients. Presented at: Ocular Microbiology and Immunology Group meeting, October 15, 2005, Chicago.