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Across the Pond | Mar 2014

Intracameral Cefuroxime as a Prophylaxis

This agent does not provide total protection against infectious organisms, but it can reduce the rate of endophthalmitis.

Endophthalmitis can cause severe vision loss after cataract surgery; only 33% of patients who develop this inflammatory condition attain a final visual acuity better than 6/12.1 Various strategies and modes of antibiotic delivery for prophylaxis of endophthalmitis have been described, of which the most promising is intracameral cefuroxime. In a telephone interview survey of 800 consultant surgeons in the United Kingdom, 79.3% reported preferring subconjunctival antibiotic injections, 13.6% intracameral antibiotic injections, and 4.1% antibiotic infusions. Of those who used intracameral antibiotics, 10% chose cefuroxime and the remaining 3.6% preferred vancomycin.2

Our surgical unit began using prophylactic intracameral cefuroxime based on recommendations from the European Society of Cataract and Refractive Surgeons (ESCRS) study authors,3 and, in the past 3 years, we have seen a reduction in our endophthalmitis rate. In order to identify the impact of the changes we made to the method of antibiotic delivery since 2006, we recently decided to analyze our historical data.

SINGLE-CENTER STUDY

Reviewing records from January 2000 through November 2009 that included 19,665 cataract surgery procedures, 28 cases of endophthalmitis were identified, confirmed, and cross-checked with the available surgical logbooks. We also analyzed vitreous tap cultures and the final visual acuities of affected patients. Only National Health Service patients operated on by consultants, fellows, or trainees at the West of England Eye Unit in Exeter, United Kingdom, were included. The department used the same phaco machines, consumables, and fluids throughout the period but replaced foldable IOLs with injectable IOL models in 2006.

Between 2000 and 2004, 12 of 8,629 patients (cumulative incidence, 0.14%) developed endophthalmitis; among the cases identified, 28% of vitreous tap cultures were positive for coagulase-negative staphylococci, 22% for viridans streptococci, and 50% had no growth. Of the patients with endophthalmitis, 33% recovered visual acuity better than 6/12, 58% better than 6/60, and 25% had no light perception. During this period, we started using povidone iodine 5% preoperatively in the anesthetic room and gave a subconjunctival injection of cefazolin at the end of surgery.

Between 2004 and 2006, another 12 cases of endophthalmitis were identified from among 4,732 cases performed (cumulative incidence, 0.25%). Among the affected patients, 38% had positive vitreous tap cultures for coagulase-negative staphylococci, 31% for other organisms, and 31% had no growth. At this time, we were participating in the multicenter ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery.3 Patients undergoing routine cataract surgery were randomly assigned to receive intracameral cefuroxime or topical levofloxacin.4

From May 2006 until November 2009, the only prophylaxis used was intracameral cefuroxime. A total of 7,006 patients underwent phacoemulsification, and only four cases of postoperative endophthalmitis were identified (cumulative incidence, 0.057%).

COMPARISON

Comparing the incidence of endophthalmitis across the three periods using the chi-square test, the results were statistically significantly different P = .019). The incidence was significantly lower from 2006 to 2009 than from 2000 to 2004 or from 2004 to 2006 (chi-square tests, P < .05), with an odds ratio (OR) for 2004 to 2006 compared with 2006 to 2009 of 4.45 (95% CI, 1.43-13.81). In total, 50% of the vitreous tap cultures from 2006 to 2009 were positive for coagulase-negative staphylococci.

The final visual outcome was better in the 2006 to 2009 period compared with the earlier audit, with 25% achieving 6/6 visual acuity, 25% with 6/12, and 50% with 6/18. None of the patients who developed postoperative endophthalmitis had risk factors including diabetes, immunosuppression, or prolonged or difficult surgery.

A HISTORICAL PERSPECTIVE

Intraocular gentamicin. Peyman et al were the first to report the use of intracameral antibiotics in 1977.5 When they introduced intraocular gentamicin as prophylaxis, the incidence of endophthalmitis decreased from a range of 3% to 6% to 0.37% in patients treated at South Indian eye camps. Likewise, when gentamicin was introduced into an irrigating solution, Gimbel et al noticed a reduced rate of bacterial infection.6

Intracameral cefazolin. Garat et al showed good outcomes with the use intracameral cefazolin (2.5 mg in 0.1 mL balanced saline solution).7 As reported in that study, cefazolin is more easily available in developing countries and costs 41% less than cefuroxime. In a study of 7,268 patients, Romero et al reported a decrease in incidence of endophthalmitis, from 0.63% to 0.055%, with intracameral cefazolin (1 mg in 0.1 mL balanced saline solution).8

Intracameral vancomycin. In an 11-year study of 16,606 cataract surgeries, Anijeet et al reported a decrease in endophthalmitis rates from 0.3% to 0.008% with intracameral vancomycin prophylaxis9. However, these authors cautioned that this antibiotic has poor efficacy against gram-positive enterocooci, targeting exclusively on infections caused by multiresistant gram-positive bacteria and the possibility of developing vancomycin resistance.

Intracameral cefuroxime. Montan et al reported a fivefold reduction in endophthalmitis with intracameral cefuroxime from large retrospective and prospective studies.10 In a prospective study of more than 225,000 patients who received prophylactic intracameral cefuroxime—and with fewer than 5% receiving topical antibiotics postoperatively—Lundstrom et al reported an endophthalmitis rate under 0.05%.4

The ESCRS study is the only published multicenter, randomized, controlled trial assessing the efficacy of intracameral cefuroxime.3 Our center was one of 24 in Europe that took part in the trial. Of 16,000 patients recruited from September 2003 to January 2006, follow-up was completed in 13,698. The incidence of endophthalmitis among those who did not receive intracameral cefuroxime was five times higher than among the patients who did (OR 4.59; 95% CI, 1.74–12.08; P = .02). Our incidence of endophthalmitis in the most recent period analyzed in this study (0.057%) is lower than that in the ESCRS study (0.073%).

A retrospective study in Sunderland, United Kingdom, including 36,743 patients showed a threefold reduction in endophthalmitis when intracameral cefuroxime was used instead of subconjunctival cefuroxime.11 In a cost-effectiveness analysis, intracameral cefuroxime was more cost-effective than topical antibiotics in the prevention of postoperative endophthalmitis. A topical fluoroquinolone such as ciprofloxacin would have to be eight times more effective than intracameral cefuroxime to achieve similar cost-effectiveness.12

CURRENT USE

A survey on the use of antibiotic prophylaxis after publication of the ESCRS endophthalmitis study found that 55% of United Kingdom & Ireland Society of Cataract and Refractive Surgeons (UKISCRS) consultant members used intracameral cefuroxime and that 48% had switched to this regimen following the publication of the report.13 In a survey of American Society of Cataract and Refractive Surgery (ASCRS) members, 77% who responded preferred postoperative topical antibiotics such as fourth-generation fluorouinolones.14

In total, 68% of respondents in the United Kingdom and 82% in the United States who did not report use of intracameral cefuroxime cited the lack of a preformulated preparation as the reason for not choosing that option for prophylaxis. Other reasons included fear of endothelial toxicity and concerns regarding bacterial contamination during preparation.

OTHER FACTORS

Surgical technique can also influence endophthalmitis rates. Studies have shown that decreased wound integrity and variable intraocular pressure are more highly associated with clear corneal incisions than with scleral incisions.15-17

Also, the choice of IOL insertion method may have an impact on endophthalmitis rate. In a 10-year retrospective study, Mayer et al found that the incidence of endophthalmitis decreased from 1.21% to 0.28% with the use of injected IOLs compared with manually folded lenses.18 They proposed that decreased contact between the ocular surface and the IOL with the use of an injector was responsible for the risk reduction.

CONCLUSION

Intracameral cefuroxime has not completely eradicated endophthalmitis. It does not provide total protection against infectious organisms, as its duration of effect in the anterior chamber is less than 24 hours. There is also risk of contamination by organisms entering the anterior chamber through unsealed wounds in the postoperative period.19 However, our findings clearly show that intracameral cefuroxime can reduce the rate of postoperative endophthalmitis, and we strongly recommend it as a prophylactic practice for cataract surgery patients. We can further prevent endophthalmitis by urging patients to adhere to their postoperative medication regimens.20

Daniel Byles, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Byles states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: daniel.byles@gmail.com.

Caspar Gibbon, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Gibbon states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: caspar.gibbon@ndevon.swest.nhs.uk.

Fiona Irvine, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Irvine states that she has no financial interest in the products or companies mentioned. She may be reached at e-mail: fiona.irvine@rdeft.nhs.uk.

John Jacob, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Jacob states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: john.jacob@rdeft.nhs.uk.

Roland Ling, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Ling states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: roland.ling@rdeft.nhs.uk.

Anthony Quinn, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Quinn states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: Anthony.Quinn@rdeft.nhs.uk.

Atul Shah, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Shah states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: abmshah@gmail.com.

Peter Simcock, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital, United Kingdom. Dr. Simcock states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: Peter.Simcock@rdeft.nhs.uk .

Michael Smith, FRCOphth, practices in the West of England Eye Unit, Royal Devon and Exeter Hospital. Dr. Smith states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: michael.smith@rdeft.nhs.uk.

Yew Chong Yap, FRCOphth, practices in the Department of Ophthalmology at the University Hospital Aintree in Liverpool, United Kingdom. Dr. Yap states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: eyapyc@gmail.com.

The authors wish to acknowledge Peter Barry, Chairman of the ESCRS Endophthalmitis study, for his review of the data presented and S. Shaw the at University of Plymouth for statistical analysis..

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