rx perspective
Fourth Generation Fluoroquinolones
Two surgeons explain why the new formulations are so promising -- and timely.

Fluoroquinolones: Still the Best Choice
By Francis Mah, M.D.

Cataract and refractive surgery have become remarkably safe and effective, thanks in part to a general trend toward decreasing postoperative infections.

However, retrospective clinical evidence from Minnesota, St. Louis and Utah now indicates a rise in endophthalmitis following clear corneal phacoemulsification. Post-LASIK infectious bacterial keratitis, especially due to the nontuberculous mycobacteria, also appears to be increasing. At the same time, in vitro studies are finding that bacteria are becoming resistant to the currently available fluoroquinolones (ciprofloxacin, levofloxacin and ofloxacin).

Nevertheless, fluoroquinolones are still the best class of antibiotic we have for preventing post-refractive surgery infections. They're broad spectrum, bactericidal antibiotics, which kill quickly, are non-toxic, and are active against atypical bacteria (a source of increasing concern among refractive surgeons). In addition, they have the best ocular penetration of any of the commercially available topical antibiotics, including Polytrim and aminoglycosides such as tobramycin.

Now, two new fourth generation fluoroquinolones -- gatifloxacin and moxifloxacin -- are under FDA investigation for ophthalmic topical use.

Controlling Resistant Bacteria

Gram positive bacteria are my primary concern when it comes to both cataract and refractive surgery because they cause the majority of postoperative infections. However, the devastating nature of atypical pathogens such as nontuberculous mycobacteria, nocardia and fungi makes them a real threat as well.

These new fluoroquinolones deal with all of these pathogens better than the current fluoroquinolones. This is especially important for post-surgical infections, which are primarily caused by the endogenous bacterial flora found periocularly. Also, the new generation have improved potency and seem to penetrate the cornea much better than the currently available agents. (Whether they'll be protective remains to be seen.)

Proactive Prevention

With or without the new fluoroquinolones, I recommend the following prophylactic regimen to help prevent infections when performing refractive surgery:

• Before surgery, pay special attention to high-risk candidates, such as patients with rosacea, blepharitis or meibomitis -- and patients with dry eyes. Remember that lid hygiene and preoperative doxycycline are critical in these patients, just as in cataract surgery.
• About 45 minutes prior to surgery, begin instilling one drop of a fluoroquinolone every 10 minutes, for a total of three to four drops.
• A Use eyelid drapes, gown, gloves and mask for every case.
• A Don't reuse blades (i.e., one eye, one blade). I use disposable instruments whenever possible.
• A Keep the procedure as simple as possible. "Less is best."
• A I don't recommend prophylactic antibiotics in the days before surgery. These patients are generally young and healthy with normal bacterial flora. Topical medications could cause an allergic response, or alter the bacterial flora and cause resistant bacteria to be selected.

At the conclusion of surgery:

• Wait 2 minutes for flap adherence; then put three or four drops of fluoroquinolone on the corneal surface and remove the speculum and drapes.

Following surgery:

• Have the patient use prednisolone acetate 1% and a fluoroquinolone every hour for the first day until bedtime.
• After the first day post-op visit, have the patient use fluoroquinolone QID for 1 week.

I use a similar regimen when performing cataract surgery.

Dr. Mah is assistant professor at the University of Pittsburgh and director of the Cornea and Refractive Surgery Fellowship at the University of Pittsburgh Eye & Ear Institute. He is also co-medical director of the Charles T. Campbell Ophthalmic Microbiology Laboratory at the University of Pittsburgh School of Medicine.

The Fourth Generation Advantage
By John R. Wittpenn, Jr., M.D.

luoroquinolones have become a key part of a refractive surgeon's armamentarium. What makes the next generation so promising is that, unlike the current drugs, they bind with gram positive bacteria at two different sites: topoisomerase four and DNA gyrase. For this reason, the new fluoroquinolones can kill organisms that are resistant to current formulations. This should also make it difficult for gram positive bacteria to develop resistance to them.

The two fourth generation fluoroquinolones currently under FDA investigation -- gatifloxacin and moxifloxacin -- appear to have clinically equivalent efficacy. Studies of pharmacodynamics and pharmacokinetics are pending.

A Change in the Wind

This is a timely development. A recent 4-year prospective analysis of 9,000 cataract surgeries at the John A. Moran Eye Center found that the rate of endophthalmitis occurrences was significantly greater than expected.

Clear cornea incisions that aren't tightly sealed could be part of the reason for this. However, in the Moran study, patients receiving ofloxacin post-surgery maintained the expected rate of endophthalmitis; patients receiving ciprofloxacin had a higher rate. This suggests that a change in resistance may be at least partly responsible.

Proactively Preventing Infection

Here are a few ways to make the most of fluoroquinolones when performing cataract surgery:

• Make sure nurses are trained to prepare the eyelashes with 5% betadine. In more than 90% of endophthalmitis cases, the organisms originate from the patients' own lids. After applying the betadine, drape the lashes away from the surgical site so they're completely out of the field.
• Create a smaller, more stable wound.
• Postoperatively, have the patient use ofloxacin QID until the conjunctiva covering the incision is firmly in place, as well as ketorolac tromethamine (Acular) QID for 1 month and prednisolone acetate (Pred Forte) QID for about 1 week. However, when making a clear corneal incision, have the patient use ofloxacin for 2 weeks after surgery. (Without a suture, manipulation of the eye can create a leak. As the anterior chamber repressurizes, it can pull fluid into the eye from the tear film, introducing the possibility of infection.)

John R. Wittpenn, Jr., M.D., practices at Ophthalmic Consultants of Long Island and is associate clinical professor of ophthalmology at the State University of New York at Stony Brook. He has no financial interest in any of the products mentioned in this article. You can reach him at (631) 941-1400 or jwittpenn@ocli.net.