Dorado Beach, Puerto Rico—Along with povidone-iodine, perioperative use of a topical fourth-generation fluoroquinolone, either gatifloxacin 0.3% (Zymar, Allergan) or moxifloxacin 0.5% (Vigamox, Alcon Laboratories), should now be considered standard of care for chemoprophylaxis in cataract surgery, said Francis S. Mah, MD, at the Current Concepts in Ophthalmology meeting.
Dorado Beach, Puerto Rico-Along with povidone-iodine, perioperative use of a topical fourth-generation fluoroquinolone, either gatifloxacin 0.3% (Zymar, Allergan) or moxifloxacin 0.5% (Vigamox, Alcon Laboratories), should now be considered standard of care for chemoprophylaxis in cataract surgery, said Francis S. Mah, MD, at the Current Concepts in Ophthalmology meeting.
Study results on resistance Dr. Mah reviewed the findings from a variety of in vitro and animal studies performed at the Campbell laboratory that demonstrated the need for the fourth-generation fluoroquinolones and their activity against ocular pathogens.
That problem was seen in testing using clinical isolates from patients with keratitis, conjunctivitis, blepharitis, and endophthalmitis.
"In one study evaluating pathogens isolated in 2001, we found 100% of Staphylococcus aureus endophthalmitis isolates were resistant to the older fluoroquinolones being used at that time for endophthalmitis prophylaxis in cataract surgery," Dr. Mah said.
Other studies show that while the third-generation fluoroquinolone levofloxacin has advantages over its predecessors with respect to improved penetration into the cornea and anterior chamber, gram-positive and gram-negative pathogens that are resistant to ciprofloxacin and ofloxacin are also resistant to levofloxacin.
"Looking at both time-kill curves and minimum inhibitory concentration (MIC) data, we found levofloxacin had no advantage over the second-generation fluoroquinolones for better activity against those organisms," Dr. Mah said.
Further research and development led to the design of the fourth-generation fluoroquinolones that feature a methoxy group at the C-8 position. That constituent confers the newer agents with an extended spectrum of antimicrobial activity characterized by improved coverage against gram-positive organisms, including fluoroquinolone-resistant ocular strains, with preservation of potency against gram-negative bacteria. As another advantage, the fourth-generation fluoroquinolones offer improved ocular penetration into the cornea and aqueous humor.
The benefits of the fourth-generation fluoroquinolones have been demonstrated in various animal studies. In a rabbit model where keratitis was produced experimentally by intrastromal challenge with a clinical keratitis isolate of methicillin-resistant S aureus, antibiotic treatment was started 4 hours later using topical gatifloxacin, levofloxacin, ciprofloxacin, vancomycin (Vancocin, Eli Lilly), cefazolin, or balanced salt solution (BSS) control applied every 15 minutes for 21 doses. The results showed gatifloxacin was superior to levofloxacin and ciprofloxacin for reducing clinical signs of infection and minimizing bacterial colony counts. It performed similarly to vancomycin and cefazolin.
"I think everyone would agree that methicillin-resistant S aureus is one of the most feared endophthalmitis pathogens and that vancomycin is the gold standard for treating this infection," Dr. Mah said. "In this study, gatifloxacin was equally effective in its antibacterial activity, but notably it has an advantage of being less toxic because, unlike vancomycin, it is formulated at a more neutral pH."
A second proof of principle study using an endophthalmitis rabbit model investigated the efficacy of topical treatment with a fourth-generation fluoroquinolone for eradicating intraocular pathogens and preventing bacterial endophthalmitis. In that experiment, animals were treated with moxifloxacin or saline every 15 minutes for 1 hour and then received injections of S aureus into the anterior chamber. An additional four doses of saline or the fluoroquinolone were administered over the next 24 hours.