With a new generation of antibiotic agents and the latest research into applications of existing medications, we're well equipped to fight pathogens facing us on the other side of the slit lamp.

Newer generation fluoroquinolones give us a larger selection of choices for treatment with increased corneal solubility and penetration. New research will give a better understanding of how to effectively treat our patients depending on the condition.

Understanding the role of next-generation fluoroquinolones and knowing when to use them will become important aspects of practice. That's why I'll explain the roles of fourth-generation fluoroquinolones, what research has revealed about them and how to use them most effectively in practice.

Meet the new generation

Fourth-generation fluoroquinolones provide a number of advantages such as better permeability, better solubility, greater concentrations and greater bacterial susceptibility.

* Better permeability. For a medication to be effective against endophthalmitis or keratitis, it's critical that it penetrates the cornea. For endophthalmitis, it's also important that the medication reaches a concentration in the aqueous. Fourth-generation fluoroquinolones accomplish both of these feats.

* Better solubility. Numerous studies show that gatifloxacin, moxifloxacin and levofloxacin have greater solubility than older generation fluoroquinolones because of their more neutral pH levels and their formulations allowing greater solubility (by the chemical formulation of the compounds). The solubility and design of these newer medications enable them to achieve far greater concentrations than older generation drugs.

* Greater concentrations. Up until recently, the only fluoroquinolones available were in 0.3% concentrations (ciprofloxacin and ofloxacin). New modifications allow concentrations of 0.5% for moxifloxacin and levofloxacin and manufacturers of levofloxacin are developing a 1.5% concentration.

An added benefit to moxifloxacin 0.5% and the levofloxacin LS% is that they'll soon be available in a self-preserved formulation, which will result in the potential of less toxicity and will make them ideal medications to prescribe to patients following surgical procedures.

* Greater bacterial susceptibility. This is one of the most important benefits of the fourthgeneration fluoroquinolones. Recent literature estimates that as many as 50% of all post-refractive surgery infections develop from atypical mycobacteria. This type of infection is often difficult to treat and following laser-assisted in situ keratomileusis (LASIK), for example, can often require flap amputation to achieve a high enough level of antibiotic concentration at the site.

A recent study by Gillespie and Billington showed that moxifloxacin is more active against a variety of mycobacteria species.

RS Donnenfeld placed rabbit LASIK eyes inoculated with Streptococcus pneumonia on either gatifloxacin or ciprofloxacin or no treatment, which was the control arm. Ciprofloxacin showed little improvement over the control (seven out of eight eyes had infiltrates vs. eight out of eight for the control), but gatifloxacin showed no infiltrates.

A study at the University of California-Los Angeles showed that the neutral pH was critical to making the drug available and for solubility and penetration of the medication into the cornea. At a pH of 7, which closely resembles that of tears, the absorption rate of levofloxacin was significantly higher than that of ciprofloxacin and ofloxacin.

An in-vivo comparison of ocular absorption also confirmed this solubility and penetration before phacoemulsification. Patients were given drops of levofloxacin or ciprofloxacin for one hour before cataract surgery. The concentration of antibiotic was measured after phacoemulsification and the conclusions showed a four to seven times greater concentration of levofloxacin in all patients.

Another study comparing gentamicin, ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin and vancomycin against the microorganism host responsible for endophthalmitis showed that moxifloxacin and gatifloxacin were equal and superior to ciprofloxacin and ofloxacin.

Now let's look at how these newer generation drugs fare against the ocular conditions we see most frequently.

Beating conjunctivitis

The use of older fluoroquinolones for treating bacterial conjunctivitis is suspect in that many bacteria, especially Gram-positive pathogens, which are common in conjunctivitis, are showing significant resistance. Usually a q.i.d. dosage regimen with any fluoroquinolone for seven to 10 days is more than sufficient to clear the condition. Educate patients about preventing the spread of the condition.

Treating peripheral ulcers

A patient presents to you with a single, grayish-white peripheral infiltrate measuring about 1.5 mm in size with 3+ conjunctival injection, an overlying epithelial defect and a 2+ anterior chamber reaction. He complains of sudden onset of pain and redness. How would you treat him?

First of all, only treat what you're comfortable treating. And keep in mind that you can never get into trouble by involving a corneal specialist. Fluoroquinolones are a first recommendation because they're some of our most potent medications, especially the newer fluoroquinolones, which have good Gram-positive coverage and usually have complete Gram-negative coverage.

Treating bacterial keratitis

You'll have the best luck treating a bacterial keratitis with a newer generation fluoroquinolone such as levofloxacin, gatifloxacin or moxifloxacin. Dose these at q. I.h. during the day following a recommended loading dose of one to two drops every 15 minutes for two hours. Some experts advocate using an ointment (such as bacitracin) overnight so the patient can rest. Doing so may also contribute to healing. Most experienced corneal specialists recommend having the patient instill a drop every two hours over the course of the night for the first night. In more severe ulcers or those that met the criteria for culturing, you may continue this regimen for a few evenings. You should also administer cycloplegic agents such as homatropine 5% or cyclopentolate 1% b.i.d. (for the same reasons listed below). The course of action for a more severe ulcer involves working with a corneal specialist, which I'll discuss now.

Dealing with severe ulcers

Prescribe cycloplegic agents for pain management and to reduce ciliary spasm and maintain blood vessel permeability. You may also want to consider prescribing oral nonsteroidal anti-inflammatory drugs (NSAIDs) for individuals who aren't already taking blood thinners or other medication that's a contraindication. Observe the patient the following day. The bacterial keratitis may appear the same or even a little worse, but the patient usually notices improved symptoms.

If the keratitis is markedly worse in signs or symptoms then refer or comanage the patient with a corneal specialist. Only after complete resolution, with no signs of epithelial breakdown or anterior chamber response, should the patient discontinue using the antibiotic drops.

Refer the following cases of bacterial infiltrative keratitis to a corneal specialist:

> The keratitis is near the visual axis > You note more than one infiltrate > The infiltrate is greater than 3 mm in size > Your patient is immunocompromised > The patient presents with the keratitis after a previous surgery > The patient is coming from a nosocomial environment.

Following culturing, it's recommended that the patient be placed on both a newer generation fluoroquinolone as well as fortified antibiotics. These medications can be alternated every 30 minutes while the patient is awake and every hour at night. Such patients should also be cyclopleged for pain management while avoiding contraindications. Prescribe pain medications depending on the level of discomfort and follow the patient daily. When cultures show stronger sensitivity to one of the two medications, the other should be discontinued. These patients should be monitored frequently because they often develop scarring that requires further treatment or surgery in the future.

The choice is clear

The neutral pH of these new fluoroquinolones and their greater solubility will decrease the precipitation of the medication and decrease burning symptoms. The decreased preservatives should also reduce toxicity and burning even further.

All of this research points to the benefit of newer generation fluoroquinolones, the importance of a neutral pH, high solubility, low toxicity and a broad spectrum of antibiotic coverage, making these medications the drug of choice in bacterial keratitis and surgical prophylaxis.

References available on request.

BY PAUL M. KARPECKI, O.D., EA.A.O. Kansas City, Mo.

Dr. Karpecki

is the director of Cornea and External Disease at Moyes Eye Center in Kansas City, Mo., and is a senior clinical consultant to Bausch & Lomb. Dr. Karpecki is also a con

sultant for Santen Pharmaceuticals.

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