Intracameral antibiotics for cataract surgery prophylaxis

ByFrancis S. Mah, MD

Endophthalmitis is among the most devastating complications associated with cataract surgery, often resulting in loss of vision or loss of the eye itself. Significant recent research has been devoted to exploring methods of preventing endophthalmitis, with some promising results. This article discusses some available methods for endophthalmitis prophylaxis, with special focus on intracameral antibiotics.

Etiology and pathology

With regard to etiology, endophthalmitis stems from primarily gram-positive bacteria. Specifically, Staphylococcus epidermidis is considered the most frequent cause. The bacteria are generally transferred from the patient’s periocular flora. They can be present on the eyelids, lashes and in the lacrimal system and, during the course of surgery, migrate into the eye and cause endophthalmitis.

Currently, the standard prophylactic strategy for endophthalmitis is the microbicide povidone-iodine applied topically in the conjunctiva and around the ocular space. The landmark study of this treatment in 1991 found a 75% to 80% reduction in the incidence of endophthalmitis with the use of povidone-iodine.¹ Specifically, two of 3,489 patients who received povidone-iodine developed postoperative endophthalmitis (0.06%) vs. 14 of 4,594 patients who did not receive the treatment (0.30%; P<.01).

Topical antibiotics

With regard to the use of topical antibiotics, prospective evidence of decreased incidence of endophthalmitis is lacking. Antibiotics can eliminate most periocular flora, which would lead to the conclusion that they could also reduce endophthalmitis incidence. Antibiotics used topically should ideally be a broad-spectrum antibiotic to cover the risk for gram-negative bacteria (which are less common but carry a worse prognosis). Also, the antibiotic must have a wide safety margin due to the significant number of patients who undergo these procedures. Pharmacokinetics must be excellent to ensure that the antibiotic actually gets inside the eye where the surgery is being performed.

It is important to remember that the only two parameters of antibiotics that define therapeutic efficacy are the mean inhibitory concentration (MIC) and the peak concentration (C_max). These parameters define the area under the inhibitory curve; the higher the C_max and the lower the MIC, the better the antibiotic (Figure).²

Pharmacokinetics/Pharmacodynamics

Figure. In terms of fluoroquinolone efficacy, three parameters exist: C_max – peak concentration, MIC, and AUIC – area under inhibitory curve. The higher the C_max and the lower the MIC, the better the fluoroquinolone.²

Source: Mah FS

Evidence in animal models suggests that a topical antibiotic helps prevent endophthalmitis. In one study, rabbits that received topical moxifloxacin had zero positive Staphylococcus aureus cultures in the anterior chamber (P=.03 vs. saline) and posterior chamber; clinical endophthalmitis scores were also zero for all of those in the moxifloxacin group.³ A similar study using gatifloxacin in rabbits was also successful.⁴

Another animal study evaluated the use of moxifloxacin to prevent S. aureus endophthalmitis following contaminated intravitreal injection of triamcinolone acetonide. This is particularly important, as intravitreal injections have been found to result in endophthalmitis rates as high as 1%. In this study, one drop of moxifloxacin solution every 15 minutes for 1 hour prior to intravitreal injection and four drops daily over the next 72 hours resulted in zero of nine rabbits showing clinical endophthalmitis. This was in contrast to six of 10 rabbits given saline solution that had clinical signs of endophthalmitis (P=.01).⁵

Intracameral antibiotics

Data from large prospective trials indicate that intracameral antibiotics may be an effective strategy for endophthalmitis prophylaxis. In 2006, preliminary results from a study that involved more than 13,000 patients at 24 sites across Europe were published by the European Society of Cataract and Refractive Surgeons.⁶

In the study, patients were divided into four groups: intracameral cefuroxime alone, perioperative topical levofloxacin alone, intracameral cefuroxime in combination with perioperative topical levofloxacin, and neither cefuroxime nor levofloxacin. All patients in the study received preoperative povidone-iodine, as well as postoperative levofloxacin, 18 hours following surgery.

Overall, the rate of endophthalmitis was 0.20% (28 cases out of 13,698 patients). Patients in the intracameral cefuroxime groups had a 0.073% rate of endophthalmitis (five out of 6,836), whereas those who did not receive intracameral cefuroxime had a 0.33% rate (23 out of 6,862). This reduction with the intracameral antibiotic is a promising result.

Importantly, however, the agents used in this study may not be the best choices. First, the current generation fluoroquinolones such as gatifloxacin and moxifloxacin have improved spectra of coverage compared with levofloxacin. Also, current generation fluoroquinolones have delayed development of antibiotic resistance and are better able to penetrate into ocular tissue.

And, although cefuroxime is as of yet the only prospectively studied intracameral antibiotic, it may not be the best choice either. It is a second-generation beta-lactam, meaning it has only average coverage of both gram-positive and gram-negative bacteria. Cefuroxime also has a high rate of resistance, meaning it would not work against any methicillin-resistant S. aureus bacteria. Furthermore, this antibiotic is a time-dependent killer; it can take 8 to 12 hours, regardless of the concentration used. In contrast, a current generation fluoroquinolone can kill within 1 hour because it is concentration-dependent.

Further research

Several smaller studies investigated current generation fluoroquinolones as intracameral prophylactic agents, but results have been mixed. One promising study conducted in the Philippines looked at the safety of using intracameral moxifloxacin solution in 65 eyes undergoing cataract surgery.⁷ The study found no ill effects with regard to endothelial cell toxicity, visual rehabilitation and anterior chamber cell/flare.

Before jumping into the use of this technique, however, it is important to remember that it is, as of yet, largely unproven, and the potential short- and long-term issues should be thoroughly examined. Perhaps most importantly, toxic anterior segment syndrome (TASS) can be caused by mislabeling or miscalculating dosages, so ophthalmologists must be sure about these agents before using them. Future research should also focus on determining the optimal drug, dosage, method of application and location, as well as short- and long-term adverse effects, of potential agents.

Summary and recommendations

Given the available information on current methods of prophylaxis for cataract surgery, what recommendations can be made? Ophthalmologists should maintain use of the standards that have been utilized for some time now because the rate of endophthalmitis in the United States is reportedly as low as the best-case scenario in the ESCRS study. Povidone-iodine has proven efficacy in reducing endophthalmitis, and sound surgical practices such as meticulous lid draping can reduce the incidence of postoperative infections. Topical antibiotic use appears to help as well, and there may be a significant paradigm shift toward the use of intracameral antibiotics when a safe, effective method becomes available for widespread use.

Complications in cataract surgery are now rare, but there are always improvements to be made. As surgeons, the goal should always be to reduce the incidence of devastating complications such as endophthalmitis down to zero.

References

Speaker MG, Milch FA, Shah MK, et al. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology. 1991;98:639-649.
Pickerill KE, Paladino JA, Schentag JJ. Comparison of the fluoroquinolones based on pharmacodynamics parameters. Pharmacotherapy. 2000;20:417-428.
Kowalski RP, Romanowski EG, Mah FS, et al. Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model. Am J Ophthalmol. 2004;138:33-37.
De Castro LE, Sandoval HP, Bartholomew LR, et al. Prevention of Staphylococcus aureus endophthalmitis with topical gatifloxacin in a rabbit prophylaxis model. J Ocul Pharmacol Ther. 2006;22:132-138.
Kowalski RP, Romanowski EG, Mah FS, et al. Moxifloxacin (Vigamox) prophylaxis prevents endophthalmitis in a rabbit model using a contaminated intravitreal injection of triamcinolone. Presented at the Ocular Microbiology and Immunology Group Meeting; November 2006; Las Vegas, Nev.
Barry P, Seal DV, Gettinby G, et al, for the ESCRS Endophthalmitis Study Group. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery. J Cataract Refract Surg. 2006;32:407-410.
Espiratu SG, et al. Evaluation of the safety of prophylactic intracameral Vigamox solution in cataract surgery patients. Presented at the 21st Congress of the Asia Pacific Association of Ophthalmology. June 2006; Singapore.