Based Upon the ESCRS Randomized Study, Should I Use Intracameral Antibiotics? Which Agent?
Eric D.
Donnenfeld,
MD
Cataract surgery is one of the most commonly performed operations in the United States, with approximately 3 million procedures performed annually.1 Modern cataract surgery has become a safe and minimally invasive procedure that continues to produce excellent outcomes. Although the incidence of endophthalmitis is extremely low, the large volume of cataract surgeries produces approximately 4000 cases of endophthalmitis per year (Figure 36-1), with potentially devastating consequences.
Figure 36-1. Endophthalmitis following cataract surgery.
The basic principles of antibiotic prophylaxis are as follows:
* To deliver an active agent effective against infecting micro-organisms
* To have adequate contact time between the drug and the infecting microbe since most antibiotics require bacterial replication to completely kill of the organism
* To avoid or minimize toxicity and side effects
* To minimize the risk of developing antibiotic-resistant organisms
* To be affordable
Antibiotic prophylaxis for the prevention of endophthalmitis in cataract surgery is one of the most controversial areas in ophthalmology. This is due to the ocular morbidity of endophthalmitis coupled with the paucity of clinical studies that conclusively show an effective technique to reduce its occurrence.
Intrinsically, the concept of placing an antibiotic into the target tissue of the anterior chamber to eradicate or partially treat the potential bacterial inoculum that occurs at the time of surgery makes sense. A number of retrospective studies have suggested that intracameral antibiotics can significantly reduce the risk of ocular infection. In the 1990s, for instance, no cases of endophthalmitis occurred in a large series of cataract surgeries where gentamicin and vancomycin were placed in the irrigation bottle.2 Today, a significant number of surgeons are using intracameral antibiotics during cataract surgery. Intracameral antibiotics can either be placed into the irrigating bottle or can be directly injected into the eye at the conclusion of the case. While placing the antibiotic into the infusion fluid may be simpler, I prefer to inject the antibiotic into the anterior chamber using a separate syringe after intraocular lens implantation. This allows me to achieve a high and reproducible concentration. This also reduces the toxicity risk of an overdose of intracameral antibiotic, which theoretically could occur from excessive irrigation volumes during prolonged surgical cases.
The most common intracameral antibiotics used today are vancomycin and tobramycin. However, these antibiotics may not be the ideal intraocular agents. Both vancomycin and tobramycin are relatively toxic and only low concentrations may be safely employed. The aminoglycosides are toxic to the retina, and clinicians have documented macula infarction following the inadvertent intracameral injection of undiluted tobramycin. Vancomycin may be associated with cystoid macular edema following cataract surgery.3 Due to the low concentrations employed and the rapid turnover of aqueous humor, there may be insufficient levels of vancomycin and tobramycin to effectively kill organisms inside the eye. The limited gram-positive spectrum coverage with the aminoglycosides and minimal gram-negative coverage with vancomycin are also of concern. Moreover, vancomycin is not the ideal intracameral agent because it is an extremely slow-acting bactericidal antibiotic. The Centers for Disease Control and Prevention has recommended that vancomycin not be used for prophylaxis in cataract surgery.
The ESCRS endophthalmitis prophylaxis study is the latest and by far the most important study to document the importance of intracameral antibiotics, specifically intracameral cefuroxime, in preventing endophthalmitis. It is the first prospective, controlled, double-masked, multicenter study to look at this issue.4 In this study, there was a 5-fold reduction in endophthalmitis in patients receiving cefuroxime as compared to patients who did not receive any intracameral antibiotic. However, another important question that emerges from this study is exactly what is the best antibiotic to use intracamerally? Cefuroxime may not be used in patients with penicillin allergy and has limited gram-negative coverage. The ideal intracameral antibiotic would be broad spectrum, bactericidal, fast acting, nontoxic, and could be supplemented with topical dosing.
Fourth-generation fluoroquinolones are concentration-dependent killers in that they must reach the minimal inhibitory concentrations (MICs) in order to be effective. Recent studies evaluating MICs have shown that this class of agents appears to cover bacteria resistant to the second- and third-generation fluoroquinolones and is significantly more potent against gram-positive and gram-negative bacteria. The fourth-generation fluoroquinolones offer several major theoretical advantages over previously employed intracameral antibiotics. Gatifloxacin and moxifloxacin, for example, have rapid bactericidal action, steep kill curves,5 and high solubility and may be absorbed into intraocular tissues to provide a more sustained release. They are less toxic to the cornea and retina, provide excellent gram-positive and gram-negative coverage, and can be supplemented by the topical administration of commercially available gatifloxacin (Zymar, Allergan, Inc, Irvine, Calif) and moxifloxacin (Vigamox, Alcon Laboratories, Inc, Fort Worth, Tex) to prolong their therapeutic aqueous concentration. In a rabbit model, Snyder et al showed that as much as 320 µg of gatifloxacin in the anterior chamber is well tolerated, with no sign of corneal clouding, glaucoma, or retinal toxicity.6
We used intracameral gatifloxacin in a single eye of 40 patients following routine cataract surgery with clear corneal incisions.7 All patients received 100 µg of the IV solution diluted in balanced salt solution (BSS) into 0.1 mL, which was injected into the middle of the anterior chamber (see Formulating Intracameral Cefuroxime below). In all cases, the eyes tolerated the antibiotic well and displayed no signs of corneal or retinal toxicity. This intracameral dose should maintain therapeutic levels 5 times longer than the same concentration of vancomycin that ophthalmologists most commonly use.
The ideal intracameral antibiotic would be broad spectrum, bactericidal, fast acting, nontoxic, and able to be supplemented with topical medications. Directly injecting intracameral antibiotic at the conclusion of surgery ensures that the dosage is both sufficient and nontoxic (toxicity can occur when the antibiotic is placed in the irrigating solution during a complex cataract extraction). In my experience, intracameral gatifloxacin appears safe in human eyes at a dosage of 100 µg in 0.1 mL. Studies are also underway to investigate the use of intracameral moxifloxacin. For now, however, based on the peer review literature, I recommend intracameral cefuroxime until controlled, masked studies have been performed with the fluoroquinolones.
Formulating Intracameral Cefuroxime
Intracameral cefuroxime is formulated by taking the IV formulation of 750 mg cefuroxime in 50 mL and diluting it with 25 mL of BSS, which results in 750 mg of cefuroxime in 75 mL or 10 mg/mL. This solution is then filtered under sterile conditions using a 0.2-mm filter. A sterile, 26-gauge irrigating cannula is attached to a sterile tuberculin syringe and 1 mg of cefuroxime in 0.1 mL is injected through the paracentesis into the center of the anterior chamber. The solution is mixed daily and used for a full day’s schedule of surgeries.
References
1. Javitt JC, Kendix M, Tielsch JM, et al. Geographical variation in utilization of cataract surgery. Med Care. 1995;33:90-105.
2. Gimbel HV, Sun R, DeBroff BM. Prophylactic intracameral antibiotics during cataract surgery: the incidence of endophthalmitis and corneal endothelial loss. Eur J Implant Refract Surg. 1994;6:280-285.
3. Blumenthal M. Prophylactic intracameral vancomycin and CME. Ophthalmology. 2000;107:1616-1617.
4. Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: preliminary report of principal results from a European multicenter study. J Cataract Refract Surg. 2006;32:407-410.
5. Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth-generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002;133(4):463-466.
6. Snyder RW, Chang M, Hare W, et al. Intraocular safety of gatifloxacin in a rabbit model. Paper presented at: The Ocular Microbiology and Immunology Group Meeting; November 15, 2003; Anaheim, Calif.
7. Donnenfeld ED, Snyder RW, Kanellopolous AJ, et al. Safety of prophylactic intracameral gatifloxacin in cataract surgery. Paper presented at: The Ocular Microbiology and Immunology Group Meeting; November 15, 2003; Anaheim, Calif.