How to evaluate the guidelines of antibiotic reactions in surgery

Eye surgeons should use intracameral antibiotics only in select situations; they should avoid aminoglycosides, and they should not use vancomycin as prophylaxis. 

Those are the guidelines Michael Jumper, MD, West Coast Retina, San Francisco, would prefer if he were having eye surgery. Dr. Jumper offered this perspective as part of an overview of antibiotics used in intraocular surgery during the Glaucoma Symposium at the 2017 Glaucoma 360 meeting. 

The rate of endophthalmitis is about 1/2,000 in intraocular surgery, Dr. Jumper said. The most common sources of infection are the lids, the adnexa, and the respiratory flora in patients receiving injections in the office. According to one estimate, 6 million intraocular injections were given in U.S. clinics in 2016.

The most common organisms are gram-positive bacteria: coagulase-negative Staphylococci, Staphylococus aureus, and Streptococcus species, he said.

According to one study, Dr. Jumper cited that on endophthalmitis vitrectomy, about 50% of patients ended up with 20/40 or better vision and 75% had 20/100 or better vision, but 5% had no light perception

Problem factors

Problem factors

Factors for the development of postoperative endophthalmitis include immunosuppression, most commonly diabetes. “Eyelid or surface disease is easy to pick up,” said Dr. Jumper. “The altered flora of things like a prosthesis or a contact lens, or even a punctal plug can have an impact on what flora are on the eye and what might be getting into the eye with an injection.

“Surgeon factors include the use of providone iodine,” he added. “The use of lidocaine jelly before the providone preparation can increase the risk.”

Vitreous lost during cataract surgery increases the risk of infection by four- or five-fold. “A patient who has a wound leak, especially if they don’t get patched at the time of surgery, can have an increased risk,” Dr. Jumpers said “Inferior wound location and silicone intraocular lens have been implicated as an increased risk factor for developing infection.”

One recent study showed that anti-vascular endothelial growth factor (anti-VEGF) injections increase the risk of endophthalmitis (delayed or acute) two- or three-fold. “It’s something I would consider when talking about antibiotics prophylaxis with a patient having cataract surgery,” said Dr. Jumper.

Providone endorsement

Providone endorsement

Dr. Jumper gave a strong endorsement of providone iodine. He cited a study in which providone reduced the risk of endophthalmitis by 75% to 80% compared to a silver compound.

“Patients will try to talk you out of using providone on their eye,” Dr. Jumper explained. “They will say they have an iodine allergy. Iodine is an element. They’ve got a lot of it in their body and they really can’t have an allergy to it.”

Patients might have a reaction and an intolerance to the betadine solution, but surgeons can get around that problem, he added.

Aminoglycosides can prove particularly dangerous, Dr. Jumper warned, with irreversible infarction one of the potential adverse reactions.

Dr. Jumper cited the case of a patient with severe intraretinal hemorrhages and no perfusion in the posterior pole. The patient had reported a penicillin allergy, but probably didn’t really have one.

Because of this concern, instead of using postoperative, subconjunctival cephalosporin, the patient received subconjunctival tobramycin. The patient suffered a toxic reaction from the tobramycin, probably because of a trabeculectomy, he said.

“Aminoglycoside toxicity is a severe thing,” said Dr. Jumper. It can occur with intravitreal injection as well as subconjunctival injections. Aminoglycoside can make its way to the back of the eye even without a trabeculectomy.

Fluoroquinolones slipping

Fluoroquinolones slipping

Fluoroquinolones kill bacteria much faster than cefuroxime, Dr. Jumper said. But they are losing their coverage as gram positive organisms develop resistance. He cited one study showing that half as many bacterial isolates are susceptible than were susceptible in the 1990s.

Cefuroxime shows more promise. A large randomized clinical trial of intracameral cefuroxime prophylaxis, conducted by the European Society of Cornea and Refractive Surgeons, showed a 5-fold reduction in endophthalmitis. “The study had to be stopped because of this big difference between the patients receiving the antibiotics and control,” Dr. Jumper said.

He noted that the rate of endophthalmitis was 1/300 in the control group. “That’s extremely high,” Dr. Jumper said. “If that was happening at the surgery center around you, that would cause a lot of concern.”

Some retrospective studies have also supported the use of the intracameral antibiotics. One study conducted at Kaiser Permanente in Northern California compared 2007 (when most patients were receiving topical antibiotics) to 2011 (when the system had switched to intracameral antibiotics). “In that period of time, there was a 22-fold reduction in endophthalmitis in that system,” he said.

By contrast, Dr. Jumper quoted a report from the Bascom Palmer Eye Institute at the University of Miami that rates of endophthalmitis were 10-fold lower without the use of intracameral antibiotics.

Antibiotics doubled

Use of antibiotics as prophylaxis has doubled among U.S. cataract and refractive surgeons since the European study, Dr. Jumper reported. Most U.S. doctors are using moxifloxacin or vancomycin off label because, in contrast to Europe, there is no approved drug for this purpose.

“That’s holding us back,” he said. “There would be even more intracameral use if there was an approved drug like there is in Europe.”

Because the only antibiotics for this purpose are available off label, patients in the United States run the risk of compounding errors. Dr. Jumper cited the example of a patient who received 60 mg of intracameral cefuroxime instead of the normal dose of 1 mg.

“That led to severe corneal, retinal, and optic nerve damage,” he said.

Possible hazards

Possible hazards

Compounding errors can create hazards with the use of vancomycin as well, and a new problem has been associated with the use of this drug in recent years: hemorrhagic occlusive retinal vasculitis (HORV).

A study of 11 such cases showed 8 eyes with 22/100 vision or worse and no light perception in 4 cases. Seven of the eyes went on to develop neovascular glaucoma.

This report prompted a task force by the American Society of Cataract and Refractive Surgery and the American Society of Retinal Specialists to investigate further. It compiled a list of 35 eyes with HORV in 22 patients.

All the patients had normal exams 1 day after their operations. But they suffered delayed onset hemorrhages in the non-perfused retina and rapid progression to neovascular glaucoma.

The researchers believe this is an immune reaction to vancomycin, probably a type III hypersensitivity reaction. There is no specific test available to determine whether a patient is sensitive to vancomycin. A skin test is available, but it is only helpful in type I and some type IV hypersensitivity reactions.

The task force recommends at minimum avoiding vancomycin with bilateral surgery. “Consider a dilated exam before the second eye surgery,” said Dr. Jumper. “Wait three weeks between eyes so you can determine whether somebody has developed this horrible problem in the interim.”

Summarizing, Dr. Jumper said if he was having intraocular surgery, he would want “a really good povidone iodine prep.” In addition, “I would make sure my lids were nice and clean.”

As for intracameral antibiotics: “If I was immune-suppressed or had diabetes, if I had been receiving anti-VEGF injections for macular degeneration or other problems, or if there was a complication during the surgery, especially vitreous loss, I would consider having an intraocular antibiotic at that time.”

He would avoid aminogIycosides in general. He would not want vancomycin for prophylaxis. “But if I had a patient with endophthalmitis, I would use it then.”