Healio
Healio
ByRosa M. Braga-Mele, MD, FRCSC
June 01, 2008
5 min read
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Proven safety profile a key feature of ideal anti-infective

ByRosa M. Braga-Mele, MD, FRCSC

Ophthalmology surgeons may become overwhelmed by the myriad of anti-infective options available to treat infection. When choosing an anti-infective, surgeons must consider the drug characteristics that are likely to produce a positive surgical outcome by preventing infection.

Physicians often regard potency against key pathogens the primary measure to differentiate anti-infectives. Mather and colleagues1 examined the potency of several generations of fluoroquinolones, including ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin, against a series of endophthalmitis isolates. The fourth-generation fluoroquinolones gatifloxacin and moxifloxacin were more potent against gram-positive pathogens that had caused endophthalmitis than older-generation fluoroquinolones such as levofloxacin, ofloxacin, and ciprofloxacin. In addition, Mather and colleagues found that moxifloxacin was more potent than gatifloxacin against gram-positive pathogens and more efficacious against fluoroquinolone-resistant organisms.

Rosa Braga-Mele, MD, MEd, FRCSC
Rosa Braga-Mele

Potency is only part of the efficacy equation, however. If an anti-infective is potent by killing pathogens at the lowest concentration but does not penetrate in the target ocular tissues, it will most likely not offer the protection required for prophylaxis and treatment of infection.

Several studies have evaluated the penetration of fluoroquinolones in the different structures of the eye. In 2006, Holland and colleagues2 found significantly higher levels of moxifloxacin 0.5% than of gatifloxacin 0.3% penetrating into all three layers of the cornea. These findings could have implications for using anti-infectives in treating patients with keratitis or for prophylaxis for patients undergoing photorefractive keratoplasty (PRK) or refractive surgery.

In 2005, a research group at the Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, reported that moxifloxacin penetrated nearly four times greater into the aqueous than did gatifloxacin.3 This finding has direct application in endophthalmitis prophylaxis for cataract patients.

Studies show newer agents are safe

In addition to being potent and penetrating target ocular tissues, the optimal anti-infective should also avoid damaging the delicate structures inside the eye.
—Rosa Braga-Mele, MD, MEd, FRCSC

In addition to being potent and penetrating target ocular tissues, the optimal anti-infective should also avoid damaging the delicate structures inside the eye. Safety is an equally important feature to consider when choosing an antibiotic. In my clinical experience, newer-generation fluoroquinolones are safe to use.

In study results published in 2005, Herrygers and colleagues4 evaluated the effects of moxifloxacin and gatifloxacin on rabbit corneal epithelium. Two dosing protocols were used: high-frequency dosing for bacterial keratitis and cataract surgery prophylaxis. Prophylaxis included preoperative dosing of four times a day for 3 days followed by 7 days of postoperative dosing. Herrygers and colleagues concluded that moxifloxacin and gatifloxacin “appear to be well tolerated by the corneal epithelium and should be considered as safe, non-toxic, bactericidal drugs, useful for a variety of clinical applications.”

In 2006, Yee and colleagues5 published study results noting that “moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution do not negatively affect the corneal wound healing process.” Forty-three patients were randomized into either a moxifloxacin group (n = 21) or a gatifloxacin group (n = 22). The fluoroquinolones were administered immediately after bilateral PRK and every 6 hours until wound healing was complete. Moxifloxacin and gatifloxacin produced no difference regarding haze, visual acuity, or corneal wound-healing rate.

Evaluating Epithelial Toxicity
Figure. Evaluating Epithelial Toxicity
Figure. Researchers using two different dosing regimens of gatifloxacin 0.3% and moxifloxacin 0.5% found no epithelial toxicity using a real-world dosing schedule.
Adapted from data published in: Price MO, Price FW, Maclelland D. Effect of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions on human corneal epithelium following 2 dosing regimens. J Cataract Refract Surg. 2005;31:2137-2141.

Also in 2006, Donaldson and colleagues6 evaluated the effect of moxifloxacin on the healthy human cornea. Fifteen patients (13 women) received 1 drop of moxifloxacin in one eye four times a day for 3 days. Patients underwent clinical, slit-lamp, and confocal microscopic examination three times during the 72 hours. The researchers concluded that “moxifloxacin causes no significant epithelial or endothelial toxicity, and has no effect on visual acuity or ocular surface integrity in healthy subjects treated using a dosing regimen that simulated prophylactic use following cataract surgery.”

Several clinical studies in humans show that moxifloxacin is safe in cataract surgery and corneal transplantation.2,3 Price and colleagues7 used two different dosing regimens in patients with healthy eyes and found no epithelial toxicity using a real-world dosing schedule (Figure). In this prospective, randomized, single-center, double-masked, parallel comparison clinical study, patients were divided into two groups. Twenty patients received gatifloxacin 0.3% in one eye and moxifloxacin 0.5% in the other eye four times a day for 7 days, whereas 24 patients received gatifloxacin 0.3% in one eye and moxifloxacin 0.5% in the other eye every hour for 10 hours. Price and colleagues found that neither gatifloxacin 0.3% nor moxifloxacin 0.5% resulted “in clinically significant epithelial toxicity in intact healthy human corneas.”

Burka and colleagues8 from the Center for Refractive Surgery Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, found no toxicity or delay in wound healing with moxifloxacin after use in a human PRK model. Thirty-five patients were included in the study, each receiving gatifloxacin in one eye and moxifloxacin in the other eye. The study concluded that “eyes treated with moxifloxacin healed faster and had smaller defects compared with those treated with gatifloxacin.”

Moxifloxacin helps ophthalmologists achieve the best possible outcome by preventing infectious complications and/or treating them.
—Rosa Braga-Mele, MD, MEd, FRCSC

This peer-reviewed literature supports not only the safety profile but also the potency and penetration capabilities of moxifloxacin as an anti-infective agent. Moxifloxacin helps ophthalmologists achieve the best possible outcome by preventing infectious complications and/or treating them. Thus, I believe it is efficacious to use a fourth-generation fluoroquinolone such as moxifloxacin 1 day preoperatively, immediately preoperatively every 5 minutes for 3 doses, and postoperatively (four times a day for 7 days) to provide optimal protection.

References

  1. Mather R, Karenchak LM, Romanowski EQ, Kowalski RP. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002;133:463-466.
  2. Holland EJ, Lane S, Kim T, et al. Human cornea and aqueous humor concentrations of moxifloxacin and gatifloxacin following topical ocular dosing with Vigamox solution or Zymar. Invest Ophthalmol Vis Sci. 2006;47. ARVO E-abstract 3577.
  3. Kim DH, Stark WJ, O’Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology. 2005;112:1992-1996.
  4. Herrygers LA, Noecker RJ, Lane LC, Levine JM. Comparison of corneal surface effects of gatifloxacin and moxifloxacin using intensive and prolonged dosing protocols. Cornea. 2005;24:66-71.
  5. Yee RW, Setabutr P, Foltermann MO, Sami MS, Chuang AZ. The effects of topical moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution on corneal healing after bilateral photorefractive keratectomy. Cornea. 2006;25:S8-S11.
  6. Donaldson KE, Marangon FB, Schatz L, Venkatraman AS, Alfonso EC. The effect of moxifloxacin on the normal human cornea. Curr Med Res Opin. 2006;22:2073-2078.
  7. Price MO, Price FW, Maclelland D. Effect of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions on human corneal epithelium following 2 dosing regimens. J Cataract Refract Surg. 2005; 31:2137-2141.
  8. Burka JM, Bower KS, VanRoekel RC, Stutzman RD, Kuzmowych CP, Howard RH. The effect of fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on epithelial healing following photorefractive keratectomy. Am J Ophthalmol. 2005;140:83-87.