Use of Intracameral Cefuroxime

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Supplement november 2014

Use of Intracameral Cefuroxime

Sunday 14 September 2014 XXXII Congress of the ESCRS London, uk

Sponsored by n 2007, results from the ESCRS At a symposium held during the XXXII ESCRS Congress in Endophthalmitis Prophylaxis Study showed London, a faculty of experts in cataract surgery and ocular Ithat intracameral cefuroxime significantly anti-infective treatments reviewed scientific principles of reduced the risk of endophthalmitis after endophthalmitis prophylaxis, reported on current practices cataract surgery [ESCRS Endophthalmitis Study in Europe, and addressed common questions regarding Group. J Cataract Refract. Surg. 2007;33:978- intracameral cefuroxime and topical antibiotic regimens for 988]. Then in 2012, a major obstacle to endophthalmitis prophylaxis. systematic intracameral use was eliminated The information in this supplement summarising the when Aprokam® (cefuroxime 50mg powder proceedings should be valuable for cataract surgeons as they for injection; Laboratoires Théa) was approved strive to optimise patient outcomes. across Europe as the first and only product indicated for intracameral administration to prevent endophthalmitis after cataract surgery. – Peter S Barry FRCS, Programme Chair As of September, 2014, this single-use agent is Consultant Ophthalmic Surgeon at St Vincent’s available in 23 European countries, with approval Private Hospital, Dublin 4, Ireland; being sought elsewhere around the world. Chairman, ESCRS Endophthalmitis Study Group

Antimicrobial Treatment Tailored to the Eye Susanne Gardner D Pharm, Specialist in Ocular Infections and Pharmacokinetics

urrent scientific rationale lends strong support to after systemic or topical administration. In addition, the intracameral injection as the preferred route drug elimination routes in the eye are unique, including of antibiotic administration for prophylaxis of post- washout through the nasolacrimal ducts after topical cataract surgery endophthalmitis, with cefuroxime administration, and aqueous humor turnover, which affect Cthe only antibiotic with an official indication for such use, drug concentrations achieved and maintained in aqueous said Susanne Gardner D Pharm. humor over time. “Direct injection of antibiotic into the anterior chamber Other factors to consider include an altered host immune assures consistent and immediate delivery of the highest response in the anterior chamber due to its relatively possible, safe dose to this target site. Thereby, peak avascular nature, and restricted direct access to the aqueous humor levels are maximised along with the anterior chamber, which emphasizes the need to develop applicable pharmacokinetic/pharmacodynamic parameters single dose versus multiple dose approaches to attaining associated with bacterial eradication,” said Dr Gardner, meaningful antibiotic levels inside the eye. specialist in ocular pharmacology and pharmacokinetics. “Information on minimum inhibitory concentration (MIC) “Regarding antibiotic selection, cefuroxime is the best values established with standard laboratory methods, option and the most frequently used agent, because it is which describe the concentration of antibiotic inhibiting the only antibiotic with clinical evidence proving efficacy microbial growth, may need to be reinterpreted as they and safety, and is the only commercially available product apply to the eye,” Dr Gardner said. with a licensed indication for prophylaxis of endophthalmitis She explained that MIC and minimum bactericidal after cataract surgery.” concentration (MBC) are values used to measure antibiotic potency and provide breakpoints at which microorganisms are considered susceptible or resistant. Notably, MBC values for cefuroxime are close to its MIC for many bacteria, and “Direct injection of antibiotic it may also have the benefit of a bactericidal mechanism of action against certain organisms due to the high into the anterior chamber concentration achieved with intracameral administration. assures consistent and However, the MIC and MBC values are determined in the laboratory where bacteria in test tubes are exposed to drug immediate delivery of the for approximately18 to 24 hours. This in vitro scenario is not necessarily representative of drug residence time in highest possible, safe dose...” the eye, Dr. Gardner said. Furthermore, the laboratory-defined MIC and MBC values are intended to relate to antibiotic concentrations that are safe and anticipated in the blood after systemic TREATMENT FUNDAMENTALS administration. Although the concentration of antibiotic Dr Gardner discussed principles of antibiotic treatment in topical formulations may far exceed the MIC and MBC as they pertain to the eye and drug delivery into the values of relevant pathogens, the concentrations achieved anterior chamber by various administration routes. She in target tissues and fluids of the internal eye are limited noted that, because of unique features of the eye, data by the corneal barrier and by routes of elimination. from the general infectious disease literature relating to Pharmacokinetics parameters used to predict antibiotic antibiotic efficacy may not translate directly to treatment efficacy include peak concentration achieved (Cmax) and or prophylaxis of intraocular infection. area under the concentration-time curve (AUC) which One issue to consider is that barriers to drug diffusion represents total drug exposure over time. Integrating into the eye limit achievable antibiotic concentrations the PK parameters with the MIC presents additional

1 Use of Intracameral Cefuroxime pharmacokinetic/pharmacodynamic parameters that help Mean AH (mcg/ml) fluoroquinolone levels quantify antibiotic effects. These include Cmax/MIC, AUC/ after topical drops MIC, area under the inhibitory curve (AUIC)/MIC, and time of exposure above the MIC (T>MIC). Moxifloxacin Gatifloxacin Levofloxacin Explaining their relevance to antibiotics used for endophthalmitis prophylaxis, Dr Gardner said that 0.5% 0.3% 0.5% 1.5% generalised guidelines from the infectious disease 4.430 Sundelin 2009 literature categorise cephalosporins as time-dependent 1.619 Bucci 2004 antibiotics for which T>MIC is important, as is the AUC. Fluoroquinolones are characterised as concentration- 0.0523 0.976 Holland 2007 dependent antibiotics with AUC/MIC or AUIC/MIC being 1.31 0.63 Solomon 2005 important parameters. However, the concept that fluoroquinolones are only “concentration-dependent” is 1.18 0.48 Kim 2005 misleading, she said. 1.74 Katz 2005 “For all antibiotics, time is an important parameter in antimicrobial effects.” 1.26 Price 2005 Dr Gardner illustrated this point by presenting 2.28 Hariprasad 2005 findings from a study investigating the time needed for two commercially available, topical fourth-generation 1.86 McCulley 2006 fluoroquinolones (gatifloxacin 0.3% and moxifloxacin 2.16 0.82 Ong-Tone 2007 0.5%) to eradicate common ocular pathogens in vitro [Callegan MC et al, Adv Ther. 2009;26:447-454]. Results 0.9 0.3 Holland 2008 showed that, for the antibiotic without added benzalkonium Figure 1 chloride (moxifloxacin), the time to eradication exceeded 60 minutes for many of the bacterial strains tested. “The difference between these two fluoroquinolones When measured one hour after the last dose, the mean in time to kill bacteria was attributed to the presence levofloxacin aqueous humor concentration reached of benzalkonium chloride (BAK) in the gatifloxacin 4.4 mcg/ml. formulation. BAK has a strong bactericidal effect in itself, “This level is higher than that reported for any but because of toxicity cannot be used inside the eye,” Dr preoperatively administered antibiotic using any dosing Gardner said. regimen (Figure 1). Yet, in the ESCRS Study, the endophthalmitis rate in the perioperative topical treatment TOPICAL VERSUS INTRACAMERAL TREATMENT group was significantly higher than in the intracameral Results of numerous studies investigating different topical cefuroxime arm,” Dr Gardner said. antibiotics with various administration regimens show “Compared with topical drops, direct intracameral that, even with multiple, frequent dosing, the aqueous injection of 1mg/0.1ml cefuroxime results in a nearly 1000- humor Cmax achieved remained low, from below 1 mcg/ fold higher aqueous humor concentration of 4000 mcg/ml. ml to about 4 mcg/ml. In addition, there is large inter- This difference is important because starting with a higher patient variability in the levels achieved. Furthermore, Cmax then increases all of the other pharmacokinetics/ results from several studies investigating various pharmacodynamics parameters associated with antibiotic antibiotic regimens show there is little or no benefit from activity, and the concentration achieved with intracameral adding antibiotic drops preoperatively to povidone-iodine cefuroxime far surpasses the MIC levels of most clinically antisepsis in terms of reducing endophthalmitis rates or isolated endophthalmitis pathogens (Figure 2).” conjunctival bacterial flora load, Dr Gardner said. She also cautioned against assuming that achieving an antibiotic concentration in internal ocular structures and Comparing AH PK/PD Parameters fluids that is merely equivalent to the MIC is adequate for efficacy. “For many years we have been targeting aqueous humor levels, content to reach between 1 and 2 mcg/ml after topical administration. However, the time of bacteria exposure to that level is limited because the antibiotic concentration diminishes parallel with aqueous humor turnover,” Dr Gardner explained. A very important point, but often overlooked, is that antibiotic levels in aqueous humor, present in the anterior chamber from preoperatively administered topical drops, is expelled at the time of the surgical incision. With that issue in mind, Dr Gardner and colleagues investigated aqueous humor concentrations achieved with postoperative drop dosing, and she compared those results with antibiotic levels reported in association with preoperative topical dosing and intracameral cefuroxime. In the study of postoperative drop dosing [Sundelin K et al, Acta Ophthalmol. 2009;87:160-165], patients undergoing phacoemulsification were administered levofloxacin 0.5% using a regimen duplicating that in the perioperative topical treatment group in the ESCRS Study (two doses 30 minutes apart preoperatively + three doses at five-minute intervals at the close of surgery). Figure 2

Use of Intracameral Cefuroxime 2 chamber. However, the concentrations utilised commonly, ranging from about 8 to 20 mcg/ml, are much lower than the concentration achieved with direct intracameral injection. “There are conflicting reports in the literature about the efficacy of this approach, but there is evidence that aqueous humor contamination can persist, even after irrigation with vancomycin and gentamicin. In addition, the irrigation may dislodge local bacteria, and it is very difficult to quantitate total drug exposure,” Dr Gardner said. “Furthermore the US Centers for Disease Control and the American Academy of Ophthalmology discourage the use of vancomycin in irrigation fluids.” (Joint Statement of the American Academy of Ophthalmology and the Centres for Disease Control Figure 3 and Prevention)

Dr Gardner also presented data using this technique, Jenkins et al. PUTTING IT ALL TOGETHER administered a cefuroxime dose of showing that with a cefuroxime Cmax Dr Gardner concluded her talk by saying 125 mg and found a mean aqueous of 4000 mcg/ml (using 0.25ml aqueous that, collectively, the information humor concentration of 20.23 mcg/ humour volume), and conservatively she presented currently provides ml, measured 12 to 24 minutes post- estimating its aqueous humor half-life mathematical and scientific support for injection [Jenkins CDG et al, Br J as one hour, the cefuroxime aqueous intracameral injection of cefuroxime Ophthalmol. 1996;80:685-688]. As humor concentration should exceed as the preferred method for cataract a comparison, Dr Gardner said that the MIC for important endophthalmitis surgery endophthalmitis prophylaxis. even when utilizing a larger aqueous pathogens for at least 10 hours post- She also reiterated there are practical humor volume of 0.3ml, the aqueous injection (Figure 3). reasons for using Aprokam. humor concentration achieved with “Aprokam is the only dosage form of direct intracameral administration ALTERNATIVE ROUTES OF ANTIBIOTIC an antibiotic with regulatory approval of cefuroxime 1mg is expected to be ADMINISTRATION for intracameral injection. Use of 3300 mcg/ml, a level that is more than A small percentage of cataract surgeons any other agent opens the door to 100-fold higher than described after use a subconjunctival injection route to medicolegal risks, and the errors subconjunctival cefuroxime 125mg. deliver antibiotic for endophthalmitis and complications associated with Addition of antibiotic to a surgical prophylaxis. In a study evaluating extemporaneous compounding,” Dr irrigating solution also delivers aqueous humor concentration achieved Gardner said. antibiotic directly into the anterior

The EurObsCat project was Changes Highlighted by the undertaken under the sponsorship of Thea and was developed by the EurObsCat After One Year European Team for the propHylaxis of Infection in Cataract Surgery (ETHICS), Béatrice Cochener MD, PhD, Professor and Chair, a group of 10 cataract surgery opinion Department of Ophthalmology, University of Brest, France leaders representing nine European nformation obtained from the Dr Béatrice Cochener, Professor and countries (Belgium, France, Italy, second wave of participants Chair, Department of Ophthalmology, Germany, The Netherlands, Poland, in the European Observatory University of Brest, France. Spain, Sweden and the UK). of Cataract Surgery Dr Cochener commented: “We have The questionnaire was designed to I(EurObsCat) point to growing uptake to thank the ESCRS for conducting the gather data on key practice performance of intracameral cefuroxime for only randomised, placebo-controlled indicators and will be administered endophthalmitis prophylaxis and in study on endophthalmitis prophylaxis annually to a cohort of surgeons. the use of the only product licensed and for providing cataract surgeons Participants are randomly selected to for this indication (Aprokam). with evidence to support a new way provide a realistic and representative Corresponding with this trend, the of thinking about prevention. Now, sample within their country if they data also show increasing influence of through the EurObsCat survey, we satisfy the requirement of performing the ESCRS Endophthalmitis Guidelines are encouraged by the increase in at least 150 cataract operations a year. as well as diminishing use of pre- and Aprokam use. Still, next year, we hope The first survey conducted in 2013 postoperative topical antibiotics. to see more surgeons are following included 479 surgeons, and its results However, the results also indicate the ESCRS guidelines and using were presented at the ESCRS Congress a need for more education about the the only antibiotic product labeled in 2013. The 2014 survey had 490 ESCRS guidelines and appropriate for intracameral endophthalmitis participants, of whom about half were regimens for medication use, said prophylaxis.” retained from the 2013 cohort.

3 Use of Intracameral Cefuroxime “The 2014 results confirmed the results from the first year, and show consistency as only half the participants were the same,” Dr Cochener said. Surgeons involved in both the 2013 and 2014 surveys were performing an average of about 520 cataract operations per year. Nearly all procedures were phacoemulsification (≥97.6%), and there was just a slight increase, from 0.5% to 1.1%, in the proportion performing femto-laser cataract surgery. However, the proportion of surgeons using a “mini” incision (1.8 to 2.1mm) increased significantly from 13% in 2013 to 18% in 2014. Multiple questions probed practices for infection and inflammation prophylaxis before the patient arrived in the operating room (OR), during surgery, and after the patient left the OR. Highlighting some of the important Figure 4 findings, Dr Cochener noted that the proportion of antibiotic used before patients arrived in the OR decreased used by more surgeons in 2014 than Responses to questions examining significantly from 42% in 2013 to 29% in 2013 (71% vs 66%); an increase medication use after the patient left in 2014. in its use for all patients rather than the OR showed a global decrease in “We think this change is due to in specific situations accounted for the proportion of surgeons prescribing increased use of intracameral antibiotic the change. Cefuroxime accounted for antibiotics (44% to 34%) and no change at the end of surgery,” Dr Cochener said. almost all intracameral antibiotic use in in anti-inflammatory use (93%). Only about one-third of surgeons 2013 (88%) and 2014 (91%), and use However, use of a fixed combination were using an anti-inflammatory agent of Aprokam as the cefuroxime of choice antibiotic+steroid was prevalent and before the patient came to the OR, almost doubled from 35% in 2013 to growing, increasing from 43% in 2013 but there was evidence of growing 62% in 2014 (Figure 4). to 59% in 2014. Of concern was the preference for a fixed combination “The increase in cefuroxime is fact that the majority of surgeons using antibiotic-anti-inflammatory (NSAID expected because of the availability the fixed combination were treating for or steroid) product accompanied by a of Aprokam, which is approved for more than two weeks, and almost half decrease in NSAID. intracameral use,” said Dr Cochener. used a tapering regimen. Use of ocular antiseptic decreased A growing proportion of surgeons said “These practices could favour prior to patient arrival in the OR and it was important to have a commercially bacterial resistance development in the increased in the OR, although Dr available broad-spectrum antibiotic future,” Dr Cochener cautioned. Cochener said the latter data may licensed for direct intracameral injection Asked what guidelines they follow have been influenced by a wording (76% to 82%), and there was a for cataract surgery, the surgeons improvement in this question. dramatic increase in the proportion cited local/hospital guidelines most Responses to questions asking about citing medicolegal protection as the frequently (41% in 2013, 38% in 2014). intracameral antibiotic showed it was reason (8% to 42%) (Figure 5). Compared with the previous year, there were increases in 2014 in the proportion of surgeons who said they followed the ESCRS guidelines (13% to 17%) or scientific society guidelines (32% to 39%), and a decrease in adherence to national guidelines (32% to 25%). “We are encouraged that the ESCRS guidelines are being progressively followed, but it seems they should be considered by even more surgeons,” Dr Cochener said. A new question in 2014 aimed to gather data on personal endophthalmitis rates. Half of the surgeons said they had at least one case of endophthalmitis in the past five years. “While the reported endophthalmitis rate is debatable, the fact that so many surgeons reported endophthalmitis in the last five years is quite significant, and especially considering that most were probably not using intracameral cefuroxime during this time,” Dr Figure 5 Cochener said.

Use of Intracameral Cefuroxime 4 Answers to Key Questions

Anders Behndig MD, Professor, Department INTRACAMERAL CEFUROXIME of Clinical Sciences/Ophthalmology, Umeå University, Sweden BACTERIAL RESISTANCE Do data from the Swedish National Cataract Register show any evidence of increased bacterial resistance to cefuroxime after such a long period of its intracameral use in Sweden? Peter Barry, Béatrice Cochener, Susanne Gardner Dr Behndig: The answer is no, and I think the explanation is that cefuroxime has less potential to drive resistance development than some other antibiotics, such as the TOPICAL ANTIBIOTIC PROTOCOLS fluoroquinolones. We do see that the proportion of Is there justification for omitting topical antibiotics infections caused by organisms that were always resistant if we are using an intracameral agent for to cefuroxime is increasing so that enterococci and endophthalmitis prophylaxis? coagulase-negative staphylococci now account for about 70% of pathogens in culture-positive cases. However, Dr Behndig: An analysis of the Swedish registry data that information should be considered in the context of showed no significant benefit of using topical antibiotics the current, very low overall endophthalmitis rate. In before and/or after surgery as an add-on to intracameral 2013, there were only 22 cases of endophthalmitis in over cefuroxime in terms of reducing endophthalmitis rates 100,000 cataract procedures, which is about one-fifth of [Friling E et al, J Cataract Refract Surg. 2013;39:15-21]. what it was in early registry years. I doubt this decrease in endophthalmitis rates would be seen if bacterial resistance What is the recommended duration of postoperative to cefuroxime was increasing over time. antibiotic treatment? However, it may also be difficult to investigate this issue in the Swedish registry data considering that during the Dr Barry: Based on the Swedish registry data, I believe prolonged period of intracameral cefuroxime use there that postoperative antibiotic use may be unnecessary. have also been changes in the surgery and characteristics However, I can’t be 100% confident about the of patients undergoing surgery. Analyses from countries postoperative integrity of the incision, and so I still use where surgeons are just now switching to intracameral a topical antibiotic and continue it for one week. The cefuroxime may better answer this question. antibiotic should not be used for more than 14 days. Such prolonged use is not necessary and will likely promote Dr Barry: Didn’t Per Montan MD, and colleagues resistance. I would also emphasise that the antibiotic in Stockholm recently switch to using intracameral should not be tapered. moxifloxacin to see if it might make a difference?

Dr Behndig: I stopped using a topical antibiotic Dr Behndig: Yes, and according to some preliminary data, postoperatively in the 1990s when I began routine use of it does not appear to have affected the endophthalmitis intracameral cefuroxime. rate. However, because the number of infections is so low, I also want to comment about the tapering issue. The it is difficult to identify a difference if it existed. EurObsCat data showing many surgeons are using a tapering regimen is very concerning. SAFETY ISSUES Dr Cochener: I agree, and perhaps the message to Have you ever experienced an episode of TASS after surgeons is to not use antibiotic-steroid fixed combination using intracameral cefuroxime? products. I also would recommend not using the topical antibiotic for more than one week. Now, we have been Dr Barry: Some minor TASS-like problems were using a macrolide with a “flash” therapy regimen involving encountered in the early days during the ESCRS study twice-daily dosing for just three days. design period, and through our investigations to identify the cause, we found it was related to dilution or diluent errors in the majority of cases. Use of balanced salt solution When do surgeons in your countries begin treatment rather than normal saline for powder reconstitution was one with the topical antibiotic? of the most common errors with the “kitchen pharmacy” Dr Behndig: Swedish surgeons who use a topical antibiotic preparation of the intracameral cefuroxime in cases where generally start on the day of surgery. patients developed TASS-like symptoms.

Dr Cochener: There is a lot of variability among surgeons Dr Behndig: Over the many years that intracameral within countries. That said, there may be a tendency in cefuroxime has been used in Sweden, we have not seen France towards using the “flash” regimen and starting it much TASS. just after the patient leaves the operating theatre. Should you inject intracameral cefuroxime in the Dr Barry: In Ireland, the topical antibiotic is generally setting of a torn posterior capsule or will it increase started on the first day after surgery, as was done in the the risk for cystoid macular oedema? ESCRS study. Some critics of the study, especially from North America, have questioned that delay and say the Dr Gardner: In a rabbit model, intravitreal injection of antibiotic should have been started sooner, on the day of cefuroxime 1mg did not cause any retinal toxicity, and there surgery or even on the day before. is an almost three-fold extra margin of safety in humans

5 Use of Intracameral Cefuroxime given the larger size of the human eye. So, even in the Dr Barry: According to my regulatory authority, surgeons worst case scenario where the entire 1mg of intracameral are prohibited from using a single-use product that is cefuroxime migrates into the back of the eye, available data intended to prevent a rare event, such as endophthalmitis, indicate there is not a safety concern. for multiple dosing because that practice exchanges one risk for another. Dr Barry: Not only is it safe to use intracameral cefuroxime However, aside from the legal and regulatory issues, I in that situation, but it is actually particularly critical believe there are other differences in terms of materials because eyes with posterior capsule rupture are at a greatly between containers that are approved for single-use increased risk for endophthalmitis. versus multi-use dosing. However, there are also clinical data to show that it is safe. When switching to intracameral cefuroxime, Shorstein Dr Gardner: That is true. The regulatory requirements and colleagues first excluded patients with posterior for manufacture of vial closures on single-use versus capsule rupture [Shorstein N et al, J Cataract Refract Surg. multiple use vials may differ among countries. The vial 2013;39:8-14]. Their endophthalmitis rate decreased, but it closure materials may therefore be different, with the dropped even further after they started to use intracameral potential for incompatibility for multiple entries into vials cefuroxime in case of posterior capsule rupture. intended for single use only. I agree that for medicolegal reasons, surgeons should not violate the instructions on Dr Behndig: In the Swedish registry, intracameral a vial labeled for single-use only. cefuroxime has been used in about 16,000 cases with a posterior capsule rupture. I think that experience supports its safety. Given the excess amount of cefuroxime in the Aprokam vial, what is the margin of safety if the surgeon inadvertently delivers a volume greater than Should intracameral cefuroxime be used in patients 0.1ml? with a history of penicillin or cephalosporin allergy? Dr Gardner: There is likely no increased risk because the Dr Barry: To my knowledge there are two cases in concentration of cefuroxime delivered into the eye remains the world literature of an anaphylactic reaction after the same. However, there is potential for toxicity using a intracameral cefuroxime injection during cataract surgery, higher concentration of cefuroxime. In an animal study, one from Spain [Villada JR et al, J Cataract Refract Surg. toxicity occurred with a concentration of 100 mg/ml, just a 2005;31:620-621] and one from Israel [Moisseiev E, 10-fold increase compared to the concentration of Aprokam. Levinger E. J Cataract Refract Surg. 2013;39:1432- This information mitigates against the use of 1434]. However, a cause and effect relationship cannot be extemporaneously compounded cefuroxime solution for established with certainty in either case. intracameral administration. The risk for cross-sensitivity with penicillin exists only for cephalosporins that share a side chain moiety with a Dr Behndig: These questions about dilution errors are penicillin. Cefuroxime does not, and the risk of there being surprising to me because at least to my knowledge, there a cross-reaction with its use in a penicillin allergic individual have not been a prominent problem during the long is essentially non-existent. history of intracameral cefuroxime use in Sweden. However, I can imagine dose and dilution errors Dr Gardner: Early in the history of cephalosporin can occur if there is a change in surgical protocol, such manufacturing, products contained trace amounts of as if surgeons switch from subconjunctival antibiotic penicillin, and that seemed to contribute to high rates of injection to intracameral use and are relying on what seemed to be cross-sensitivity. Cephalosporin product extemporaneous compounding. contamination with penicillin has been eliminated through better manufacturing processes. Dr Barry: In Sweden you have operated with intracameral cefuroxime and kitchen pharmacy for many years without Dr Behndig: We ask our patients only about a history of any problem because it is a routine that is familiar to all allergy to a cephalosporin, not to penicillin, and patients of the staff. However, if the protocols change, problems with cephalosporin allergy are very rare because in recent can arise if there is not good communication with and years, cephalosporins have not been used much for education of all personnel involved. systemic antibiotic therapy in Sweden. On that basis, I There is a published report from Finland describing eight expect we will see even fewer patients with a cephalosporin patients who were blinded after receiving 50-100 mg/ allergy in the future. ml intracameral cefuroxime [Olavi P. Acta Ophthalmol. 2012;90:e153-4]. The error occurred because when Dr Cochener: In France, we also only ask about directions for preparing the solution were sent by the cephalosporin allergy. manufacturer, only two pages of the three page fax were received. The take home message from this and other real- APROKAM USE world examples is that surgeons who have access to The reconstituted Aprokam vial contains 50 mg/5ml, Aprokam should seriously reconsider a decision to use but the dose administered is just 1 mg/0.1 ml. Does anything else. the remainder have to be discarded, or can it be used for other patients? Dr Cochener: In some countries, including France, Dr Cochener: The product is marketed for single-use physicians can be prosecuted for using a product off- only, and for medicolegal reasons should not be used for label for a particular indication when there is an available multiple dosing. alternative licensed for that use.

Use of Intracameral Cefuroxime 6 Supplement november 2014 WREPORESCRS2014