Rx Perspective
Toward an Ideal Ocular Antibiotic
The currently available fluoroquinolones were a big advance for ophthalmology, and we're about to take another step forward.

BY HAROLD R. KATZ, M.D.

We are now in an exciting period with our ability to treat ocular infections, an area of ophthalmology that is of critical importance. For some time now, we've had access to ophthalmic fluoroquinolones, and the next generation of these medications is currently being developed.

The ideal ocular antibiotic would give us:

• a broad spectrum of activity
• a low incidence of resistance
• penetration to the site of infection and sustained therapeutic levels
• rapid killing of bacteria
• comfort
• minimal toxicity.

WHY THE FLUORQUINOLONES?

The fluoroquinolones afford us many of the benefits listed above. Therefore, we can use them to successfully treat blepharitis, bacterial conjunctivitis and corneal ulcers, and they're an excellent choice for surgical prophylaxis.

They're broad-spectrum, bactericidal, kill bacteria rapidly, have minimal toxicity and minimal systemic absorption. They work by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. These enzymes are used by bacteria to maintain DNA in a supercoiled state. The inhibition of these enzymes results in uncoiling of bacterial DNA, resulting in death of the bacteria and their inability to replicate.

Resistance to the fluoroquinolones develops slowly because a bacterial mutation must occur. With other antibiotics, the transmission of a small piece of genetic material (called a plasmid) from resistant bacteria to other bacteria enables them to become resistant.

A Pseudomonas aeruginosa ulcer before (above) and after treatment with ciprofloxacin.

THE THINKING BEHIND MY CHOICES

Norfloxacin is the least potent of the topical fluoroquinolones and is not being marketed in the United States.

The other fluoroquinolones, ciprofloxacin (Ciloxan), ofloxacin (Ocuflox) and levofloxacin (Quixin), can all be used to treat conjunctivitis. Levofloxacin has been approved by the FDA for treating bacterial conjunctivitis, but it doesn't have a corneal ulcer indication. For corneal ulcers, I prefer ciprofloxacin because it has been shown to be the most effective against Pseudomonas aeruginosa, which is the most common cause of culture-positive contact lens-related bacterial keratitis.

(In cases of severe bacterial keratitis, I believe that cultures should be ordered. With cultures, we can identify the organism causing the infection and obtain antibiotic sensitivities. We can then make the best choice in antibiotic therapy for that infection.)

Ciprofloxacin is also available as an ointment, which makes it a good choice for the treatment of Staph blepharitis.

Because none of the currently available fluoroquinolones is capable of achieving a sustained therapeutic intraocular concentration with topical dosing, their role in surgical prophylaxis is to eradicate ocular surface flora preoperatively and postoperatively.

I prefer ciprofloxacin for prophylaxis because it rapidly kills bacteria on the ocular surface -- 97% reduction in ocular surface flora in 15 minutes. (Snyder-Perlmutter, Katz, J of Cat and Refract Surg, 11/2000)

NEXT GENERATION IS IN THE PIPELINE

Moxifloxacin and gatifloxacin, two fluoroquinolones that have recently been approved for systemic use, are undergoing clinical trials for use as topical ophthalmic antibiotics. They have a number of potential advantages over the presently available fluoroquinolone antibiotics.

They're much more active against gram-positive organisms, especially Streptococcus. They maintain excellent gram-negative coverage, although they may not be quite as potent against Pseudomonas aeruginosa as ciprofloxacin.

There is also evidence that these antibiotics may be effective against organisms resistant to presently available fluoroquinolones. A paper presented at the Ocular Microbiology and Immunology Group meeting at the AAO last year compared the in vitro activity of moxifloxacin, gatifloxacin, levofloxacin, ofloxacin and ciprofloxacin against 98 endophthalmitis bacterial isolates. The results showed that moxifloxacin had the most in vitro activity against gram-positive endopthalmitis isolates and in addition was active against those isolates resistant to the presently available fluoroquinolones.

As it looks now, this new generation of ophthalmic fluoroquinolones will be a giant step forward in our ability to treat and prevent ocular infections.

Dr. Katz is the director of Cornea, External Disease and Refractive Surgery at the Krieger Eye Institute in Baltimore and an assistant professor of ophthalmology at the Wilmer Eye Institute. He writes and lectures frequently on ocular infections, antibiotics, cataract surgery and refractive surgery.