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EW NEWS & OPINION 21 Otherwise, the drug's use in fungal endophthalmitis patients will do more harm than good E ven when a tough case of endophthalmitis occurs, physicians would do well to remember the phrase, "First, do no harm." Recently, several patients with fungal endophthalmitis injected with amphotericin B as a treatment wound up with severe intraocular toxicity. Although amphotericin B is a mainstay of treatment for fungal en- dophthalmitis, the potential for in- traocular toxicity is very real—and also very preventable. "We present 3 cases of intraocu- lar toxicity from highly concen- trated amphotericin B," reported Timothy W. Olsen, M.D., Emory Eye Center, Atlanta, in an article from the Archives of Ophthalmology. "In every case, the overly concen- trated amphotericin B solution was yellow in color. We feel that physi- cians should carefully observe the color of the solution and be cautious in the dosing of amphotericin B for the treatment of fungal endoph- thalmitis. If the solution has a yel- low color, then the solution should not be injected." Three cases that never should have happened In one case, an 11-year-old boy pre- sented with delayed onset traumatic endophthalmitis after being hit in the left eye with a dart. "The surgeon inspected the am- photericin prior to injection and noted that it was 'bright yellow,'" Dr. Olsen reported. "The pharmacist, who was contacted, reassured the surgeon that amphotericin B is yel- low and that the dosing was correct. The medication was therefore in- jected." Visual acuity deteriorated to counting fingers on the first day post-op, vitreous inflammation in- creased, and a new lenticular opacity emerged. Subsequent problems in- cluded inferior rhegmatogenous reti- nal detachment, proliferative vitreoretinopathy, and others. Addi- tional surgical procedures were re- quired, and 3 months after initial presentation, the patient's BCVA was 20/80, stabilizing to 20/30 six years later. It was found that while the physician had requested a dose of 5 micrograms/0.1 mL from the pharmacy, the actual mixture was undiluted amphotericin B (500 micrograms/0.1 mL). In a second case, a 45-year-old man presented with fungal endoph- thalmitis in his right eye and as part of treatment was subsequently in- jected with amphotericin B on mul- tiple occasions with a concentration thought to be 5 micrograms/0.1 mL. The concentration was later in- spected because a yellowish quality was noticed, and it was found to contain 55 micrograms/0.1 mL. The damage had been done. Eventually the patient experi- enced retinal detachment, but with additional surgical procedures, was correctable to 20/60. In a third case, a 65-year-old pa- tient who recently had extracapsular cataract extraction presented with presumed endophthalmitis. As part of treatment, amphotericin B was administered. "Prior to the intravitreal injec- tion of amphotericin B, it was noted that the syringe was 'too yellow,'" Dr. Olsen reported. "The pharmacist was contacted, and the dilution was confirmed. Because the surgeon did not feel comfortable with the color of the medication, he only injected 40% of the initially intended dose." The subsequent morning, the patient experienced severe ocular pain in the left eye. There was also considerable inflammation. With treatment, the patient's vision slowly recovered, and he was cor- rectable to 20/30 two years later. The concentration of ampho- tericin B, meanwhile, was discovered to be 400 micrograms/0.1 mL instead of 4 micrograms/0.1 mL. "By injecting 40% of the in- tended dose, the patient received 160 micrograms of amphotericin B," Dr. Olsen reported. These were unfortunate scenar- ios and highly preventable. "The purpose of this study is to warn clinicians that highly concen- trated doses of amphotericin B may be recognizable and avoidable," Dr. Olsen noted. "In our series of case reports, the treating physician noted that the amphotericin appeared yel- low in every case." Research has found that doses of amphotericin B greater than 25 micrograms are exceedingly toxic, leading to retinal detachment. "Because amphotericin B alters the permeability of cellular mem- branes, it was felt that the retinal de- tachments were partially caused by transudation of fluid into the sub- retinal space," Dr. Olsen noted. Routine doses of amphotericin B are only 5-10 micrograms for fungal endophthalmitis. "Physicians should pay close at- tention to the color of amphotericin B prior to an intravitreal injection, and they should question or discard any solution that appears too yel- low," Dr. Olsen concluded. Bjorn Johansson, M.D., Linkoping University Hospital, Sweden, said that's a good tip. "I'm not sure that those who administer drugs [at our hospital] consider that the yellow color [of amphotericin B in high concentra- tion] is a sign of danger," Dr. Johansson said. "I'll bring that up to the clinic. That's an interesting point." Currently, however, he believes standing instructions at the clinic are that the amphotericin B solution should be clear. EW Editors' note: Dr. Johansson has no financial interests related to his com- ments. Dr. Olsen has no financial interests related to this study. Contact information Johansson: bjorn.johansson@lio.se Olsen: tolsen@emory.edu September 2011 by Matt Young EyeWorld Contributing Editor If amphotericin B is yellow, don't use it An example of endophthalmitis Source: Huyn Van, M.D. Ophthalmic antibiotics can cause antimicrobial resistance A ntibiotics used in patients with wet age-related macular degeneration is associated with antimicrobial resistance, according to new research published in the September issue of Archives of Ophthalmology (2011;129(9):1180-1188). Stephen J. Kim, M.D., and Hassanain S. Toma, M.D., both from Vanderbilt University School of Medicine, Nashville, studied 48 eyes of 24 patients who received an intraocular injection in one eye each. Pa- tients were randomized to one of four antibiotics, ofloxacin, azithromycin, gati- floxacin, or moxifloxacin hydrochloride. "Coagulase-negative staphylococci (CNS) cultured from eyes repeatedly exposed to fluoroquinolone antibiotics demonstrated significantly increased rates of resistance to older-generation and newer-generation fluoroquinolones," the researchers wrote. "In contrast, CNS isolated from azithromycin-exposed eyes demonstrated significantly in- creased resistance to macrolides and decreased resistance to older-genera- tion and newer-generation fluoroquinolones."

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