Endophthalmitis study results confirm role of cefuroxime in reducing infection risk

Cefuroxime seems to be particularly protective against streptococci, which are the cause of extremely severe infection.

Prophylactic intracameral cefuroxime injection effectively reduces the rate of endophthalmitis after phacoemulsification cataract surgery, according to the final results of the ESCRS Endophthalmitis Study, disclosed at the European Society of Cataract and Refractive Surgeons meeting by Peter Barry, FRCS, study chairman and 2006 Ridley Medal Lecturer.

“Cefuroxime injection lowers the chances of bacterial contamination by a factor of five. This means that the risk rate is reduced to less than five in 10,000 cases,” Dr. Barry said.

Other findings concerning risk factors, the most common contaminating organisms and the efficacy of diagnostic tests were illustrated.

Study design

The study involved 24 centers in nine European countries. Data were collected from September 2003 until January 2006. A total of 15,971 patients were recruited and followed, making this “the largest study of an antibiotic in the history of medicine,” Dr. Barry noted.

Peter Barry, FRCS, presented results of the ESCRS Endophthalmitis Study at the organizations annual meeting. Image: Schultz J, OSN

Patients were randomly distributed into four groups. In group A, patients received intensive topical placebo drops and no injection of antibiotics. In group B, patients received the same intensive topical placebo drops and an intracameral injection of cefuroxime (1 mg in 0.1 mL saline solution) at the end of surgery. In group C, patients received intensive topical levofloxacin antibiotic drops and no injection. In group D, patients received the intensive levofloxacin drops and the injection of intracameral cefuroxime.

“All patients in all groups received povidone iodine preoperatively, as we consider that it was the only prophylaxis with an evidence-based efficacy,” Dr. Barry said.

The lens implanted after phacoemulsification was a choice made by each participating surgeon. Acrylic IOLs were the majority, accounting for nearly 75%, followed by silicone (25%) and a small number of other lenses.

Topical antibiotic drops were administered postoperatively three times a day for 6 days to prevent the risk of wound infection.

The endpoint of the study was the occurrence of infective endophthalmitis. Initially this was diagnosed clinically and therefore classified as presumed. Any suspected case underwent testing by gram stain, culture and polymerase chain reaction (PCR).

Efficacy of cefuroxime injection

In group A, there were 13 presumed infections, nine of which were proved. In group B, there were three presumed infections, two of which were proved. In group C, there were 10 presumed infections, seven of which were proved. In group D, there were two presumed infections, one of which was proved.

“If we combine the results of group A and C, who received no cefuroxime injection, there were 23 presumed infections, 16 of which were proven. Combining group B and D, which received the injection, there were five presumed infections, three of which were proven. This shows that the utilization of the injection effectively reduces by a factor of five both the presumed and proven cases,” Dr. Barry said.

Intracameral cefuroxime can therefore reduce the rate of endophthalmitis to less than five in 10,000 cases.

He noted that the observed rate in the group that received minimal treatment with placebo drops and no injection (33 per 10,000 presumed and 23 per 10,000 proved) was higher than that in literary reviews.

“We suggest the reason is that retrospective studies are prone to underreporting,” he said.

Staphylococci and streptococci were the principle organisms found across the four groups.

Of the 11 staphylococcal infections, only three occurred in the groups of patients that received cefuroxime injection. Of the eight streptococcal infections, none occurred in the injected groups.

“If we look at the final visual outcome in relation to these two principle organisms, we can see that the final visual acuity in 11 cases of staphylococcal infection ranged from 20/20 to 20/80. None of the patients was legally blind. On the other hand, the final visual acuity of the eight cases of streptococcal infection ranged between 20/20 and no light perception. Five of the study cases in this group are legally blind due to streptococci. None of these received cefuroxime,” Dr. Barry said.

He deemed this a “powerful result,” as cefuroxime seems to be particularly protective against streptococci, which are the cause of extremely severe infection, often leading to legal blindness.

Cefuroxime not available for ophthalmic use

Dr. Barry noted that cefuroxime is not licensed for intraocular use. To utilize it in the study, a special exemption certificate was required, which expired when the study ceased recruiting patients.

“We have a paradox,” he said. “Normally a clinical trial is performed on a new drug provided by a pharmaceutical company to physicians to prove its efficacy and safety. Here we have the antithesis of a clinical trial: We have the results, but no drug.”

In most countries, a physician can use cefuroxime off-label and take the responsibility for doing so, he said.

“But in practical terms, taking 750 mg of cefuroxime powder and diluting it by yourself to a concentration of 1 mg in 0.1 mL saline exposes you to all the risks of kitchen pharmacy, with errors in dilution, a possible induction of toxic anterior segment syndromes and the frightening possibility of contamination, for example with Pseudomonas, against which cefuroxime is not effective,” Dr. Barry said.

He appealed to the industry to provide ophthalmologists with single sterile unit doses of cefuroxime for the millions of cataract procedures that are performed annually worldwide.

Other findings

The contribution of PCR in proving suspected endophthalmitis was shown to be crucial in this study.

“In all the cases except those in which it was not performed for technical reasons, PCR confirmed positive culture and positive gram stain testing. In several other cases, we had a positive PCR with a negative culture and a negative gram stain. Without PCR, these cases would have remained in the presumed category rather than transferring into the proven,” Dr. Barry said.

Besides failure to inject cefuroxime, other risk factors of endophthalmitis were clarified by the ESCRS study.

“Implantation of a silicone IOL as opposed to acrylic was found to increase by a factor of four the chances to get endophthalmitis. The utilization of a clear corneal incision instead of scleral tunnel fell just under statistical significance but cannot be ignored. The use of intensive levofloxacin drops did not achieve statistical significance,” Dr. Barry said.

Results of such a large study are highly reliable, he said. They should persuade cataract surgeons to use intracameral cefuroxime as a standard part of their procedure.

The use of intracameral cefuroxime as an antibiotic prophylaxis agent was suggested by Swedish research, which proved the efficacy and safety of cefuroxime in a high number of patients. Also, the choice of levofloxacin rather than the new fourth-generation fluoroquinolones was suggested by the positive results of 30 million doses used in Japan.

“We consider that vancomycin and the fourth-generation fluoroquinolones should be strictly reserved for treatment,” Dr. Barry said.

For more information:

• Peter Barry, FRCS, can be reached at Royal Victoria Eye & Ear Hospital, Adelaide Road, Dublin 2, Ireland; 353-128-37203; fax: 353-128-38229; e-mail: peterbarryfrcs@eircom.net.

• Michela Cimberle is an OSN Correspondent based in Treviso, Italy, who covers all aspects of ophthalmology. She focuses geographically on Europe.