Antibiotic prophylaxis reduces risk of endophthalmitis

ByManfred Tetz, MD

Ophthalmologists have been performing intraocular surgery for more than 50 years. In that time, many treatments and regimens were used in clinical trials to reduce the risk for developing endophthalmitis. Currently, many ophthalmologists agree that rinsing the conjunctival sac with a povidone iodine solution is one of the best preoperative prophylactic treatments. Study results find that using a povidone iodine solution largely reduces the number of organisms in the conjunctival sac.^1-4

A debate exists among ophthalmologists about the use of antibiotic eye drops for endophthalmitis prophylaxis. Studies provide contradictory recommendations on when to begin treatment. A number of surgeons recommend using antibiotics 1 or more days preoperatively, whereas others believe that preoperative antibiotic use could breed resistant organisms. Some ophthalmologists suggest that preoperative treatment kills normal flora while pathogens survive. In my experience, I have discovered that most surgeons prefer to administer antibiotic eye drops for endophthalmitis prophylaxis at the time of surgery, rather than 1 or more days preoperatively.

First large-scale study on prophylaxis

Manfred Tetz

Investigations such as the nonrandomized study performed by Montan and colleagues⁵ and the randomized European Society of Cataract and Refractive Surgeons (ESCRS) study⁶ suggest that intracameral injection of cefuroxime at the end of cataract surgery can significantly reduce the incidence of endophthalmitis. The ESCRS study was the first performed on a large number of patients to determine conclusively the most efficacious prophylaxis to prevent endophthalmitis. Before this study, no standard regimen for preventing endophthalmitis was widely accepted.

The ESCRS study was the first performed on a large number of patients to determine conclusively the most efficacious prophylaxis to prevent endophthalmitis.
—Manfred Tetz, MD

The ESCRS study enrolled 15,971 patients from 23 clinics. The patients were divided into four groups. Each group received different treatments, but all patients received povidone iodine preoperatively and topical levofloxacin postoperatively for 6 days. One group received vehicle drops perioperatively but did not receive an intracameral injection of cefuroxime. Another group received placebo drops and an intracameral injection of 1.0 mg of cefuroxime in 0.1 mL of saline at the end of surgery. A third group received levofloxacin eye drops perioperatively but did not receive an intracameral injection. The fourth group received both perioperative levofloxacin eye drops and intracameral cefuroxime.

The ESCRS study results show that the use of intracameral cefuroxime reduced the risk for developing endophthalmitis approximately fivefold. It should be noted, however, that general risk for endophthalmitis in these patients was already reduced compared with patients who do not receive povidone iodine prophylaxis. Because all other variables were considered constant, the study investigators concluded that intracameral cefuroxime reduced the risk of endophthalmitis. Furthermore, the study was terminated earlier than planned because of the significantly different outcomes in the incidence of endophthalmitis. The investigators determined that all patients should receive intracameral cefuroxime.

The ESCRS study was one of the most reliable because of the large number of patients evaluated. However, the study design had flaws. First, the ESCRS study lacked appropriate testing of all potential combinations or noncombinations. This was likely an ethical decision because investigators cannot treat a control group without any type of coverage. Another flaw in the ESCRS study was that the incision site may have played a role in the results because some studies find a higher incidence of endophthalmitis in patients with clear corneal incisions.^7-9 Perioperative use of levofloxacin, however, was not shown to have influenced study outcomes.

Pathogen coverage and topical antibiotic use

Ophthalmologists assume that the risk of endophthalmitis could be reduced further with a more effective antibiotic.
—Manfred Tetz, MD

Acute-onset endophthalmitis, usually within the first 1 to 3 weeks postoperatively, may be attributable to a variety of organisms but is often caused by the more virulent ones. Cefuroxime is effective against most staphylococcal species, Escherichia coli, Proteus species, Propionibacterium, which usually causes low-grade endophthalmitis, Klebsiella, and Haemophilus influenza. However, cefuroxime does not protect against methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus strains and is weak against Pseudomonas. Also, due to the aqueous turnover, the concentration of cefuroxime in the anterior chamber may decline by a factor of four in approximately 1 hour.¹⁰ Cefuroxime is a slower, time-dependent bactericidal antibiotic and may take longer to eradicate bacteria even when a high concentration of antibiotic is achieved. Other agents, such as fluoroquinolones, are concentration dependent and achieve faster kill kinetics.¹¹

During the ESCRS study’s planning and running phases, third-generation topical fluoroquinolones, such as levofloxacin, were state-of-the-art treatments. Today, with knowledge of the efficacy of newer fluoroquinolones and resistant development, investigators would likely have used a newer-generation fluoroquinolone such as moxifloxacin (Vigamox, Alcon Laboratories, Inc.) or gatifloxacin (Zymar, Allergan). Whether a newer topical fluoroquinolone would have affected study outcomes is difficult to determine. It is unclear how much of the prophylaxis is attributable to the disinfection with povidone iodine, the intracameral use of cefuroxime, or the additional perioperative fluoroquinolone eye drop regimen. The ESCRS study does not conclusively answer these questions. It is likely that the more effective the perioperatively administered antibiotic, the less likely it is that endophthalmitis will occur.

The ideal antibiotic for reducing the risk of endophthalmitis must have a good bactericidal spectrum and also should have good pharmacokinetics allowing for high concentration of antibiotic in the ocular structures.
—Manfred Tetz, MD

Complications such as postoperative endophthalmitis are becoming less acceptable as more cataract surgeries become refractive procedures. It is mandatory that surgeons offer patients the most efficacious prophylaxis possible. Newer-generation fluoroquinolones are more effective than third-generation fluoroquinolones and, as always with new antibiotics, have developed less resistance. Although the literature on the potential benefits of administering topical antibiotics preoperatively is inconclusive, ophthalmologists assume that the risk of endophthalmitis could be reduced further with a more effective antibiotic that has lesser resistance and a broader spectrum. The ideal antibiotic for reducing the risk of endophthalmitis must have a good bactericidal spectrum that also covers resistant strains and should have good pharmacokinetics allowing for high concentration of antibiotic in the ocular structures, particularly cornea and aqueous humor. To allow for a broader usage, the ideal agent would also have a physiological pH, no risk of toxicity, and a reduced risk of allergic response.

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