番茄社区

CHICAGO – All but one of 12 patients given injections of contaminated bevacizumab (Avastin) prepared by a compounding pharmacy in Florida permanently lost vision in the affected eye, researchers reported here.

Neither early nor late vitrectomy improved visual outcomes, and seven patients lost the eye completely in the endophthalmitis outbreak that occurred in Miami in July 2011, Roger Goldberg, MD, of the New England Eye Center at Tufts University, and colleagues reported at the American Academy of Ophthalmology meeting.

Ophthalmologists are "very reliant on compounding pharmacies, not just for Avastin but for all preservative-free formulations and intravitreal antibiotics," said Goldberg, who was working at the University of Miami when the outbreak occurred.

"So to some extent we need to figure out ways to safely prepare these medications," he continued. "And it obviously begs the question that's been the main story here -- how to best ensure medications that pass through compounding pharmacies are safe."

Compounding pharmacies have come under increased scrutiny, including congressional hearings, with the ongoing meningitis outbreak -- 461 cases and 32 deaths -- caused by injections of contaminated methylprednisolone acetate made by a compounding pharmacy in Massachusetts.

Oversight of these entities currently falls to the states, but legislators have been calling for stronger federal regulation, including giving FDA clearer authority over compounders.

In the Miami endophthalmitis outbreak, Goldberg said 12 patients arrived in the ophthalmic emergency department within 6 days of getting an intravitreal injection of bevacizumab – nine of them arrived within 48 hours of having the shots.

They'd all been treated by four community retina specialists in Miami-Dade and Broward counties over 4 days, and all of the bevacizumab syringes had been prepared by a single compounding pharmacy, Goldberg said.

Cultures for 10 patients came up positive for Streptococcus mitis or oralis, matching the strains in seven unused syringes prepared during the same time by the compounder.

An FDA investigation of the company revealed insufficient testing and monitoring of equipment, dirty lab equipment, a failure to maintain sterilization tools, and a leaking boiler near the clean room.

Compounders have been at the center of other contamination issues. Earlier this year, Franck's Compounding Lab in Ocala, Fla., was linked with 33 cases of fungal infections resulting from intravitreal injections of Brilliant Blue G dye and triamcinolone.

Goldberg told 番茄社区 that with the rise of expensive, branded intravitreal anti-VEGF agents that come in appropriate doses, such as ranibizumab (Lucentis), the "need for Avastin syringes safely aliquoted from 4- or 16-mL vials into the tiny doses used in the eye has further increased our reliance on compounding pharmacies and the critical role they play in the care of our patients."

But therein lies the increased risk of contamination, according to Joel Zivot, MD, director of the cardiothoracic ICU at Emory University Hospital Midtown in Atlanta, who wasn't involved in the study.

"Every time something that is sterile is handled, the opportunity for contamination increases. It would be impossible to get the contamination rate to zero," Zivot said. "Perhaps what will be needed are further safeguards on the prescribing side, including some testing to reduce the chance of delivering a contaminated product to the patient."

Goldberg warned ophthalmologists to thoroughly check out a compounding pharmacy before they buy from it, doing their best to ensure the company is in compliance with USP-797, the current national standard of practice.

He added that clinicians should also document all lots of the drug and syringes they buy, as well as keep accurate patient contact records in case they need to be notified quickly.

Wiley Chambers, MD, of the FDA, who was in the audience when the data were presented, noted that one patient had bilateral administration of bevacizumab, but one eye did not get infected.

That's because only one of the syringes was from the contaminated compounder, Goldberg said. The other, a last-minute addition, came from a different compounding pharmacy.

"Perhaps the lesson," Wiley said, "is never use the same lot for bilateral injection."

Goldberg agreed, but noted that greater, coordinated oversight in terms of safety is the ultimate goal.

"The most concerning feature to me is that compounding pharmacies are regulated by the state, and states have different rules, regulations, and commitments to oversight and enforcement," he told 番茄社区. "This introduces unwanted variation into the compounding process."

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