Fluroquinolones. They're readily available.
Fortified Antibiotics. They give broad coverage.

Editor's note: This "Great Contact Lens Debate" argues which therapy is best for a contact lens wearer with these specific symptoms: 3-4mm mid-peripheral ulcerative keratitis, with moderate surrounding edema, significant overlying epithelial defect, minimal anterior chamber reaction and 360-degree conjunctival injection.

Fluroquinolones. They're readily available.

by Randall Thomas, O.D., Concord, N.C.

With a known bacterial infection, most doctors concern themselves with the offending microbe, especially if it's Pseudomonas. This is the most dreaded bacterial pathogen to the cornea and one of the most common in contact lens wearers. But you'd have to culture the eye to determine which bacteria you're dealing with, and such knowledge has been shown to be unnecessary in most cases. You need to make a decision immediately and begin a therapy that's broad enough to cover the common pathogens.

For this patient I would choose topical fluoroquinolones. Studies clearly show that the vast majority of corneal bacterial pathogens respond to these drugs. The key is to mount an aggressive and intensive attack. Anything less and the infection might not resolve.

I would prescribe either of the two premier fluoroquinolones: Ciloxan (ciprofloxacin) or Ocuflox (ofloxacin), currently the only two fluoroquinolones indicated for treating bacterial corneal ulcers. Recent studies find that these medications are as effective, if not more so, than the combination fortified therapy of tobramycin and cefazolin.^1,2 While there are many studies that show the superiority of one fluoroquinolone over the other, I am convinced that both are equally efficacious.

An aggressive therapy includes using one drop every 15 minutes for the first 3-5 hours to saturate the cornea and rapidly curtail bacterial proliferation. Anything less might be sub-optimum.

In this case I would have the patient instill the drops every hour during the daytime for 2-3 days until the epithelial defect decreases to 1mm. At bedtime, I'd have the patient use Polysporin (polymyxin B and bacitracin). The bacitracin is an excellent gram-positive killer, while the polymyxin B is effective against gram-negative organisms, including Pseudomonas.

I would also cycloplege the eye daily with a 0.25 percent scopolamine or 5 percent homatropine to help prevent any secondary inflammation. Cycloplegia helps stabilize uveal vessels and relaxes the iris to provide more comfort to the patient.

I'd follow the patient daily for 4-5 days until I saw significant resolution of the keratitis. Once that occurs, I would decrease the dosage from hourly to four times a day for 4-5 days. I would have the patient continue using the ointment at bedtime, as well, and would continue to see the patient for two more days. At that time I would expect the epithelial defect to be nearly healed.

Once the epithelial defect has decreased to 1mm and you begin tapering the therapy, you might want to add Lotemax (loteprednol etabonate) 2-4 times daily to minimize scarring and enhance visual outcome.

Fluoroquinolones are a relatively new class of antibiotics, having been on the market for about five years. They are particularly effective in treating moderate to severe conjunctival and corneal bacterial infections. Their chemical structure and unique pharmacology make them the most effective of today's available ophthalmic antibiotics. They inhibit bacterial DNA gyrase, an enzyme necessary for replication. Even in standard concentrations, they are highly bactericidal. Studies have suggested that some gram-positive pathogens resist topical fluoroquinolones, but that resistance has largely been shown to depend on the drug concentration, such as under-dosing.

Further, fluoroquinolones are readily available; they don't have to be strengthened or formulated by a pharmacist the way fortified antibiotics do. They provide the patient with the ease of single-agent therapy; they're immediate availability off-the-shelf and come pre-packaged, so you're of their sterility. Some studies have found that fluoroquinolones are less toxic than fortified antibiotics and that patients achieve greater comfort.^1,3

Since round-the-clock antibiosis is wise in all cases of bacterial keratitis, selecting Polysporin is an excellent adjunct to fluoroquinolone therapy because of its gram-positive and gram-negative coverage. Should you want double coverage against gram-positive pathogens, instill Polysporin twice a day and at bedtime. I would only advocate switching to fortified antibiotics if this therapy clearly wasn't working.

1. Ciprofloxacin Bacterial Keratitis Study Group. Comparison of ciprofloxacin ophthalmic solution 0.3 percent to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ophthalmol 1996;103(11):1854-1863.
2. Bacterial Keratitis Study Research Group. Efficacy of ofloxacin vs. cefazolin and tobramycin in the therapy for bacterial keratitis. Arch Ophthalmol 1995;113(10):1257-1265.
3. The Ofloxacin Study Group. Ofloxacin monotherapy for the primary treatment of microbial keratitis: a double-masked, randomized, controlled trial with conventional dual therapy. Ophthalmol 1997;104(11):1902-1909.

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Fortified Antibiotics. They give broad coverage.

by Ron Melton, O.D., Charlotte,  N.C.

Note: Staphylococcus and Streptococcus are Latin names for these species of bacteria, so their initial caps, italic. Staphylococcal and streptococcal are the English derivatives of those words and are used as adjectives. No initial caps, no italics.

With an ulcerative keratitis, time is of the essence. While all potentially serious corneal ulcers should be cultured, I agree that you can't wait for culture results to begin therapy. Delaying only increases the likelihood of scarring and threatens vision.

Unlike my colleague, however, I would opt for the standard therapy for corneal ulcers: fortified antibiotics. This combination has had a long and, more importantly, successful track record of offering broad spectrum coverage over both gram-positive and gram-negative organisms, critical in hastening recovery and in providing patient comfort.1 In fact, several studies have shown an emerging resistance of Staphylococcus, Streptococcus, Enterococcus and Anaerobic bacteria to fluoroquinolones. ^2,3

For this patient I would prescribe a fortified aminoglycoside, such as tobramycin 0.9 percent, which gives excellent coverage against gram-negative bacteria, including Pseudomonas.

I would complement this with a fortified gram-positive cephalosporin, such as cefazolin, which is highly effective against the staphylococcal and streptococcal species. I have no doubt that this combination provides the most comprehensive coverage against the most common ocular bacterial pathogens. These two fortified antibiotics in tandem has traditionally had a 98 percent cure rate.⁴

I would recommend one drop every 30 minutes, alternating between the two agents while the patient is awake. For overnight use I would prescribe Ciloxan (ciprofloxacin).

I would have this patient cycloplege daily with homatropine 5 percent, and I would evaluate the patient until the corneal defect was less than 1mm. Then I would decrease both antibiotics to four times a day and would see the patient in two days. I would also continue the patient on the Ciloxan at bedtime.

Once you get culture results and you've identified the infectious organism, you can eliminate one of the antibiotics to minimize toxicity. By that time, however, you'll already have a good clinical picture as to whether the ulcer is responding to the therapy you have prescribed. If your initial mitral therapy is inadequate, you can switch to more effective antibiotics, such as amikacin for gram-negative strains and vancomycin for gram-positive coverage.

If the corneal infiltrate compromises the visual axis, I would add prednisolone 2-4 times each day once the epithelial defect was less than 1mm.²

Animoglycosides work by inhibiting protein synthesis. They're especially potent against gram-negative bacteria, such as Pseudomonas. They can become toxic with long-term use, but they're rarely used long enough to produce toxic side effects in cases such as this. Cephalosporins work by inhibiting bacterial cell-wall systhesis. The first generation cephalosporins are particularly effective against gram-positive organisms. Because some bacteria have become increasingly resistant to standard concentrations of antibiotics over the years, it's very important to use a fortified combination of both of these agents for maximum therapeusis.

One caveat in prescribing: Because the fortified antibiotics have to be individually formulated by the pharmacist for each patient, it's important to know beforehand which pharmacies in your can provide this service competently and expediently.

1. Laibson PL. Cornea: New Choices for Therapy of Corneal Disease. Yearbook of Ophthalmology. St. Louis: CV Mosby, 1996:39-41.
2. Bacterial Keratitis. Preferred Practice Pattern. American Academy of Ophthalmology. 1995:9-11.
3. Knauf HP, et al. Susceptibility of corneal and conjunctival pathogens to ciprofloxacin. Cornea 1996;15(1):66-71.

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Drs. Thomas and Melton were named Glaucoma Educators of the Year for 1997 by the American Academy of Optometry, of which they are both fellows. They are full-time practitioners and adjunct faculty members of the Pennsylvania, Pacific University and State University of New York Colleges of Optometry. They are consultants to the AOA and their 20-hour course, "Current Therapy in Ocular Disease" is offered four times a year throughout North America."