Injections raise safety question

Key Points

Orlando, FL-Nationally publicized outbreaks of Streptococcus endophthalmitis following intravitreal injection of bevacizumab (Avastin, Genentech) resulted in a close look at the procedures used to prepare the drug.

Roger A. Goldberg, MD, MBA, described the outbreaks and the steps that Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, takes to minimize the risk of contamination during syringe preparation. He presented this information during Retina Subspecialty Day at the annual meeting of the American Academy of Ophthalmology. An outbreak of 12 cases began in July 2011 when a patient presented to the emergency department at Bascom Palmer Eye Institute with light perception visual acuity, an IOP of 42 mm Hg, and a marked anterior chamber reaction. The patient had received an intravitreal injection of bevacizumab 2 days previously by a retina specialist in the community.

Ten cases were positive for Streptococcus mitis/oralis, and seven unused syringes were also positive for the organism. All of the contaminated syringes had been prepared by the same compounding pharmacy. The CDC, FDA, and state and local agencies investigated the source of the contamination, according to Dr. Goldberg.

"The visual outcomes have been poor," said Dr. Goldberg, an ophthalmologist at Bascom Palmer Eye Institute. "Two patients have undergone evisceration, and another underwent enucleation. Eight patients underwent vitrectomy, at which time the retinas were noted to be necrotic, the optic nerves pallorous, and the vessels sclerotic. Only one patient recovered her pre-injection visual acuity. One patient received bilateral injections, but the fellow eye was injected with bevacizumab prepared by a different compounding pharmacy and endoph thal mitis did not develop."

Other such outbreaks of endophthalmitis also occurred in a private practice in Nashville, TN (five patients); at the Veterans Affairs (VA) Hospital, Nashville, TN (four patients); in a private practice in Minneapolis (five patients); at the VA Hospital, Sepulveda, CA (five patients); and in a university in Seoul, Korea (two patients).

"Each outbreak was traced back to the compounding pharmacy that prepared the bev aciz u mab syringes," Dr. Goldberg said.

As a result of the outbreaks, the FDA issued an alert on repackaged bev a ciz u mab, and the VA Administration put a temporary nationwide hold on the use of the drug in the eye.

"A big factor in this is that bevacizumab is used off-label to treat neovascular diseases," he said. "It is important to understand where and how the contamination might be occurring with [bev a ciz u mab], which is a much cheaper drug than ran i biz u mab [Lucentis, Genentech]."