August 2007

 

CATARACT/ IOL

 

Intracameral antibiotics ... surgeons not yet convinced


by Rich Daly EyeWorld Contributing Editor

   

Surgeons want more efficacy, research, and an FDA-approved single use intracameral injection before adopting this measure

Most surgeons remain unconvinced that a switch to intracameral antibiotics during cataract surgery is worth the risk without further study, according to a recent ASCRS membership survey.

The anonymous 2-minute online survey, was conducted by the ASCRS Cataract Clinical Committee earlier this year. The survey link was emailed to the ASCRS global membership and 1,312 surgeons responded. The ASCRS Cataract Clinical Committee aimed to assess the impact of the 2006 ESCRS endophthalmitis prophylaxis study on surgeons’ clinical practice. The widely publicized ESCRS study found that intracameral injection of Ceftin (cefuroxime, Glaxo SmithKline, United Kingdom) significantly reduced the occurrence of post-op endophthalmitis compared to the control group.

“This was a landmark multicenter study that proved the efficacy of intracameral cefuroxime prophylaxis,” said David F. Chang, M.D., clinical professor, University of California, San Francisco, and chair, ASCRS Cataract Clinical Committee. “The practical implications are controversial, however, because the antibiotic must be mixed off label, and because the control group had an unusually high incidence of endophthalmitis.” The ESCRS study included two control sub-groups. One received Tavanic (topical levofloxacin, OrthoMcNeil, Raritan, N.J.; in Europe, marketed by Sanofi Aventis, Paris) one hour before surgery and at the end of surgery, while the other sub-group received no perioperative topical antibiotics. Post-op Tavanic was started the day after surgery in both control sub-groups.

ESCRS study impact limited

“We initiated this membership survey in order to see what cataract surgeons are currently doing for antibiotic prophylaxis, and to assess the impact of the ESCRS study on their practices,” said Dr. Chang. The survey found that 16% of cataract surgeons were already injecting intracameral antibiotics at the conclusion of cataract surgery prior to the ESCRS study, and additional 7% had begun or planned to begin doing so as a result of the study. However, 77% had no plans to initiate intracameral antibiotics as recommended by the study’s authors.

“The question one could ask is why this large, randomized, prospective study, which showed a 5-fold reduction in endophthalmitis rate when intracameral cefuroxime was used, has not had a greater impact on clinical practice patterns,” Dr Chang said. “One major reason seems to be the fact that we don’t have a Federal Drug Administration (FDA)-approved commercial antibiotic preparation for intraocular use?”

The survey, which was first presented by Dr. Chang at the 2007 ASCRS•ASOA Symposium and Congress, specifically asked those surgeons still not using intracameral antibiotic injections to list their reasons and concerns. For this subgroup of respondents, 89% were awaiting more research, 45% cited mixing risks and 17% were concerned about increased cost.

Dr. Chang, said he was not surprised about the continued hesitancy toward intracameral antibiotics because the unavailability of a commercial single-use intracameral injection and the necessity to self-mix the injections create the potential for dilution errors, microbial contamination, and toxic anterior segment syndrome (TASS). Those concerns over homemade solutions were probably heightened by the national outbreak of TASS cases last year. The ASCRS survey found those concerns were not unfounded because among surgeons using self-mixed intracameral antiobiotics, either added to the infusion bottle or directly injected, 14% reported having experienced complications from this practice. The most common complications listed were inflammation (57%) and corneal endothelial injury (42%). Infection was reported by 4% and “other” complications were listed by 23% of surgeons who reported having experienced a complication from using intracameral antibiotics.

“We’ve seen many cases where TASS has resulted from surgeons trying to custom mix any kind of material that they are going to inject into the eye,” said Nick Mamalis, M.D., professor of ophthalmology, Moran Eye Center, University of Utah, Salt Lake City. “So certainly it would allay surgeons’ concerns if there was an approved commercially available single-use injectible antibiotic to put into the eye after each case.”

Although no companies have announced plans to submit such a single use intracameral injectable antibiotic for FDA approval, 47% of surgeons said they would use such a product, and another 35% said they would consider its use based on the cost.

Majority of surgeons use topical antibiotic prophylaxis

Dr. Chang speculates that another major reason surgeons have not more broadly adopted the ESCRS findings first published in March 2006, according to the survey results, was the fact that it did not compare intracameral antibiotics to the current topical prophylactic antibiotic regimen of most surgeons. For example, the ASCRS survey found that among the 91% of all surgeons using perioperative topical antibiotics, most (81%) use Zymar (gatifloxacin, Allergan, Irvine, Calif.) or Vigamox (moxifloxacin, Alcon, Fort Worth, Texas). The ESCRS study did not utilize these fourth-generation fluoroquinolones which provide a broader spectrum of coverage than earlier generation counterparts because Zymar and Vigamox are generally not available in Europe, where the multicenter study was carried out. According to the ASCRS survey, only 3% of respondents currently use topical levofloxacin, as was used in the ESCRS study control group. Rounding out the topical antibiotic preferences, 9% of surgeons use either Ocuflox (ofloxacin, Allergan) or Ciloxan (ciprofloxacin, Alcon), and 7% use other unspecified agents.

Besides the antibiotic agent, the ESCRS study also did not reflect current dosing practices for topical prophylaxis, according to Dr. Chang. The ASCRS survey showed that 88% of surgeons are using topical antibiotics preoperatively. Fifty two percent initiate them three days before surgery and 26% begin them one day before surgery. Only 22% wait until the day of surgery to start pre-op topical antibiotics. In contrast, one half of the ESCRS control group patients did not receive any topical antibiotic preoperatively, while the other half received topical levofloxacin immediately prior to surgery.

The ASCRS survey found that most surgeons (90%) also administer antibiotic via some route at the conclusion of surgery. Eighty three percent use topical antibiotics, and smaller groups use subconjunctival (13 %) and intracameral injections (15%) or a collagen shield (3%). The survey also found that among the 98% of surgeons using topical antibiotics post-op, the majority (66%) start them on the day of surgery and the remainder (34%) start them the day after surgery. Only one half of the ESCRS control patients received topical antibiotic at the conclusion of surgery, and postoperative topical antibiotics were not started until the day after surgery for all control subjects. “Because the ESCRS control group does not at all reflect the most common topical antibiotic practices of ASCRS members, we do not know whether intracameral antibiotics are superior to, or of any additive benefit to topical prophylaxis alone”, concluded Dr. Chang. “A similar type of study comparing intracameral antibiotics to topical antibiotics in this country would go a long way toward answering the questions raised by this survey,” said Dr. Mamalis, a member of the Cataract Clinical Committee. Dr. Mamalis said the massive costs and organizational challenges of such a study would probably keep it from occurring. Also still unanswered is whether a fourth-generation antibiotic injected intracamerally would provide better protection than cefuroxime.

Francis S. Mah, M.D., medical director, Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh School of Medicine, said some surgeons have debated the quality and validity of the ESCRS study because its size was insufficient, due to the broad group of patients included. A better study, he said, would include only patients with a single type of surgical approach and eliminate all cataract patients who had complications.

Long-term studies also are needed to show intracameral, injected drugs have no unforeseen consequences.

Intracameral use detailed

Despite the unavailability of commercial preparations, the ASCRS survey found that overall, intracameral antibiotic prophylaxis by some route is used by 31% of ASCRS respondents with 48% of them placing antibiotic in the infusion bottle and 52% directly injecting them. When intracameral antibiotics are used, they are either mixed by an operating room nurse (77%), a pharmacist (18%) or the surgeon (5%). As noted earlier, among those using intracameral antibiotics, 14% reported having had a complication from doing so. That degree of complications among intracameral recipients is important, Dr. Mah said, because safety concerns are at the heart of surgeons’ hesitation to use that antibiotic approach.

“If you are trying to prevent a problem that happens once in 1000 cases with a solution that has problems 14% of time, then what kind of solution is that?” Dr. Mah said. The survey found that among surgeons who use intracameral antibiotics, most surgeons (61%) use vancomycin (various manufacturers). The remainder use cephalosporins (23%; various manufacturers), a fluoroquinolone (22%; various manufacturers) or another drug (12%).

Other cataract trends identified

Dr. Chang also noted the survey finding of similar endophthalmitis rates reported by surgeons for topical and intracameral injected antibiotics raised the possibility that surgeons already perceive that their endopthalmitis rate is already quite low thanks to topical antibiotics prophylaxis. Ninety percent of respondents listed their endophthalmitis rate as < 1/1000. Only 3% of respondents had a rate of 0.3% or higher, which would have been comparable to that of the ESCRS control group.

“Is it necessary on top of [topical antibiotics] to add intracameral antibiotics? That’s a question the ESCRS study didn’t answer and that I think every surgeon needs to decide this for themselves,” Dr. Chang said. “If surgeons are already achieving the same low endophthalmitis rate as the intracameral cefuroxime group by using topical fourth-generation fluoroquinolones, they must weigh the risk of adding home made intracameral antibiotic in this context. Mark Packer, M.D., associate clinical professor, Casey Eye Institute, Oregon Health & Science University, Portland, Ore., said the impact of an aggressive use of topical antibiotics found in the ASCRS survey should not be underestimated. Topical antibiotic protocols, such as starting pre-op antibiotics three days prior to surgery, have resulted in an infection rate of zero in more than nine thousand consecutive cases at his surgery center. “Since this rate is lower than that in the ESCRS treatment group I have not considered changing it,” said Dr. Packer, who also is a member of the Cataract Clinical Committee.

Of the 98% of surgeons using topical antibiotic postoperatively 73% stop them within one week. A minority of ophthalmologists (19%) use topical antibiotics for several weeks post-op without tapering them and 8% will taper them off over a period of several weeks,. Fifty-four percent of the ASCRS survey respondents felt that it was important to have a commercially available antibiotic preparation for intracameral injection. Eleven percent felt this was not important, and the remaining 35% stated that they were not sure. Dr. Mah said delineating the current practice for most surgeons also may help researchers to acquire the research funding from government agencies needed help refine the prophylaxis of such drugs.

Editors’ note: Dr. Mah is has financial interests with Allergan (Irvine, Calif.), Alcon (Ft. Worth, Texas), Inspire Pharmaceuticals (Durham, N.C.), and Insite Vision (Alameda, Calif.). Drs. Chang, Mamalis and Packer reported financial interests related to their comments.

Contact information
Chang: 650-948-9123, dceye@earthlink.net
Mamalis: (801) 581-6586, nick.mamalis@hsc.utah.edu
Mah: 412-647-2214, Mahfs@upmc.edu
Packer: 541-687-2110, mpacker@finemd.com

Intracameral antibiotics ... surgeons not yet convinced Intracameral antibiotics ... surgeons not yet convinced
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