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Endophthalmitis
FROM THE EDITOR
Endophthalmitis Endophthalmitis is the scourge of cataract surgeons but fortunately is a rare, although serious, event. Infection origin is almost always exogenous, which means the infecting organism gains access to the inner eye during surgery or early in the postoperative period. Asepsis and antisepsis are the keys to operative risk; ocular hygiene and topical antibiotic agents are the key to eliminating postoperative risk. Despite attempts to sterilize the ocular surface prior to surgical intervention, several studies have confirmed that bacterial contamination may survive the operative session1,2 and thereby gain access to the inner eye during surgery. Thereafter, wound security or lack of it may allow ingress of bacterial contamination, including suture presence or removal in the early postoperative period.3,4 Topical antibiotic therapy at the conclusion of a cataract operation may have limited ocular penetration to counter potential bacterial ingress and limited duration of effect on the ocular surface. Intracameral antibiotic agents, on the other hand, are there to counteract inadvertent bacterial contamination during surgery and up to an hour postsurgery, as many studies now confirm their efficacy. The European Society of Cataract and Refractive Surgeons (ESCRS) performed a prospective multicenter trial of postoperative endophthalmitis after cataract surgery5 and reported a rate of 0.07% of presumed infectious endophthalmitis after intracameral cefuroxime treatment versus a rate of 0.34% in control groups. In this issue, Garcı´a-Sa´enz et al. (pages 203–207) report an infectious endophthalmitis rate of 0.043% (95% confidence interval [CI], 0.02%-0.06%) from October 2005 to December 2008 with intracameral cefuroxime compared with a rate of 0.59% without cefuroxime, confirming the outcome of the ESCRS multicenter study. The efficacy of intracameral cefuroxime as a prophylactic measure against infectious endophthalmitis is now well established. It is not a perfect prophylactic because of limited efficacy against gram-negative bacteria. Cefuroxime is not available in prepackaged form for intracameral use; it has to be diluted from concentrate in the operating room, giving scope for errors in dilution and contamination. Cefuroxime is a second-generation cephalosporin from compounds that were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu.6 He noticed that these cultures produced substances that were effective against Salmonella typhi, the cause of typhoid fever, which had beta-lactamase. BetaQ 2010 ASCRS and ESCRS Published by Elsevier Inc.
lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotic agents such as penicillins, whereas cephalosporins are relatively resistant to beta-lactamase. Cefuroxime exerts antibacterial activity by inhibition of bacterial cell wall synthesis in susceptible species. In the ESCRS multicenter study,5 in the proven infective endophthalmitis cases, the absence of cefuroxime and the use of silicone intraocular lens (IOL) optic material and clear corneal incisions were significantly associated with an increased risk and there was evidence that men were more predisposed to infection. The absence of an intracameral cefuroxime prophylactic regimen at 1.0 mg in 0.1 mL normal saline was associated with a 4.92-fold increase (95% CI, 1.87-12.9) in the risk for total postoperative endophthalmitis. Is There a Downside to Intracameral Cefuroxime in Cataract Surgery? Is It Safe? A severe anaphylactic reaction has been reported 5 minutes after 1.0 mg of cefuroxime was injected into the anterior chamber after routine phacoemulsification and IOL implantation.7 The patient, who had a known allergy to penicillin, recovered well after immediate resuscitative action was taken, emphasizing the need for immediate availability of trained resuscitation staff in the operating room. However, immunoglobulin E-mediated allergy to cefuroxime is rare in the cataract population. Intracameral cefuroxime 1.0 mg appears safe in terms of local toxicity. It achieves high aqueous concentrations even 1 hour after surgery.8 What Happens to the Macula and Fovea During and After Cataract and IOL Implantation Surgery and Does Cefuroxime Have Any Effect? In a study of foveal and perifoveal thickness measured by optical coherence tomography after phacoemulsification and IOL implantation, the initial (preoperative) mean value of 234.1 G 2.6 (SEM) (n Z 536) in the 6.0 mm perifoveal region increased to 242.5 G 2.6 mm (n Z 488) (P!.01) at 1 week, 247.7 G 4.6 mm (n Z 352) (P!.01) at 1 month, and 246.0 G 5.9 mm (n Z 208) (P!.05) at 2 months. However, the relative change in macular thickness was moderated3.5%, 5.6%, and 5.3%, respectively. There was no reported correlation between macular thickening and visual acuity.9,10 Cefuroxime 1.0 mg intracameral use in a double-masked clinical study showed no significant difference in postoperative macular thickness.11 0886-3350/10/$dsee front matter doi:10.1016/j.jcrs.2009.12.013
191
192
FROM THE EDITOR
How Cost Effective Is the Use of Intracameral Cefuroxime in Preventing Endophthalmitis After Cataract Surgery? In a recently reported study, Sharifi et al.12 concluded that owing to their high costs, the many commonly used topical antibiotic agents are not cost effective compared with intracameral cefuroxime, even under optimistic assumptions about their efficacy. Efficacy was defined as the absolute reduction in rate of infection from background rate of infection, sourced from the ophthalmic literature. The most expensive topical fluoroquinolones studied, gatifloxacin and moxifloxacin, would have to be more than or equal to 19 times more effective than intracameral cefuroxime to achieve cost-effective equivalence.
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What Has Been the Effect of the Positive Findings of the ESCRS Multicenter Trial of the Efficacy of Intracameral Cefuroxime in Cataract Surgery on Surgeon Protocols? The ESCRS endophthalmitis study published preliminary results in 200613 showing a near 5-fold decrease in the rates of postoperative endophthalmitis with the use of intracameral cefuroxime. The findings generated considerable controversy and 1 year later, its recommendations had been heeded by only 6% of ASCRS members.14 A United Kingdom survey sought to gauge the uptake among surgeons in the U.K. Fiftyfive percent of respondents were using intracameral cefuroxime; 48% had switched after publication of the ESCRS study. Of those remaining, 68% reported their main concern was the risk for dilution errors in the absence of a commercially preformulated preparation, with 67% stating they would switch if such a product became available.15 Emanuel Rosen, FRCSE
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REFERENCES 1. Tervo T, Ljungberg P, Kautiainen T, Puska P, Lehto I, Raivio I, Ja¨rvinen E, Kuusela P, Tarkkanen A. Prospective evaluation of external ocular microbial growth and aqueous humor contamination during cataract surgery. J Cataract Refract Surg 1999; 25:65–71 2. Mistlberger A, Ruckhofer J, Raithel E, Mu¨ller M, Alzner E, Egger SF, Grabner G. Anterior chamber contamination during
15.
cataract surgery with intraocular lens implantation. J Cataract Refract Surg 1997; 23:1064–1069 Lee BJ, Smith SD, Jeng BH. Suture related corneal infections after clear corneal cataract surgery. J Cataract Refract Surg 2009; 35:939–942 Kelly SP, Ajit RR, Glenister HM. Hazards of redundant corneal sutures: a safety message [letter]. J Cataract Refract Surg 2004; 30:1151–1152 ESCRS Endophthalmitis Study Group. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg 2007; 33:978–988 Bo G. Giuseppe Brotzu and the discovery of cephalosporins. Clin Microbiol Infect 2000; 6(suppl 3):6–9 Villada JR, Vicente U, Javaloy J, Alio´ JL. Severe anaphylactic reaction after intracameral antibiotic administration during cataract surgery. J Cataract Refract Surg 2005; 31:620–621 Montan PG, Wejde G, Setterquist H, Rylander M, Zetterstro¨m C. Prophylactic intracameral cefuroxime; evaluation of safety and kinetics in cataract surgery. J Cataract Refract Surg 2002; 28:982–987 Biro Z, Balla Z, Kovacs B. Change of foveal and perifoveal thickness measured by OCT after phacoemulsification and IOL implantation. Eye 2008; 22:8–12. Available at: http:// www.nature.com/eye/journal/v22/n1/pdf/6702460a.pdf. Accessed November 21, 2009 von Jagow B, Ohrloff C, Kohnen T. Macular thickness after uneventful cataract surgery determined by optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2007; 245:1765–1771 Gupta MS, McKee HDR, Saldan˜a M, Stewart OG. Macular thickness after cataract surgery with intracameral cefuroxime. J Cataract Refract Surg 2005; 31:1163–1166 Sharifi E, Porco TC, Naseri A. Cost-effectiveness analysis of intracameral cefuroxime use for prophylaxis of endophthalmitis after cataract surgery. Ophthalmology 2009; 116:1887–1896 Barry P, Seal DV, Gettinby G, Lees F, Peterson M, Revie CW. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; preliminary report of principal results from a European multicenter study; the ESCRS Endophthalmitis Study Group. J Cataract Refract Surg 2006; 32:407–410 Chang DF, Braga-Mele R, Mamalis N, Masket S, Miller KM, Nichamin LD, Packard RB, Packer M. Prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2007 ASCRS member survey; the ASCRS Cataract Clinical Committee. J Cataract Refract Surg 2007; 33:1801– 1805 Gore DM, Angunawela RI, Little BC. United Kingdom survey of antibiotic prophylaxis practice after publication of the ESCRS Endophthalmitis Study. J Cataract Refract Surg 2009; 35:770– 773
J CATARACT REFRACT SURG - VOL 36, FEBRUARY 2010
Endophthalmitis Endophthalmitis is the scourge of cataract surgeons but fortunately is a rare, although serious, event. Infection origin is almost always exogenous, which means the infecting organism gains access to the inner eye during surgery or early in the postoperative period. Asepsis and antisepsis are the keys to operative risk; ocular hygiene and topical antibiotic agents are the key to eliminating postoperative risk. Despite attempts to sterilize the ocular surface prior to surgical intervention, several studies have confirmed that bacterial contamination may survive the operative session1,2 and thereby gain access to the inner eye during surgery. Thereafter, wound security or lack of it may allow ingress of bacterial contamination, including suture presence or removal in the early postoperative period.3,4 Topical antibiotic therapy at the conclusion of a cataract operation may have limited ocular penetration to counter potential bacterial ingress and limited duration of effect on the ocular surface. Intracameral antibiotic agents, on the other hand, are there to counteract inadvertent bacterial contamination during surgery and up to an hour postsurgery, as many studies now confirm their efficacy. The European Society of Cataract and Refractive Surgeons (ESCRS) performed a prospective multicenter trial of postoperative endophthalmitis after cataract surgery5 and reported a rate of 0.07% of presumed infectious endophthalmitis after intracameral cefuroxime treatment versus a rate of 0.34% in control groups. In this issue, Garcı´a-Sa´enz et al. (pages 203–207) report an infectious endophthalmitis rate of 0.043% (95% confidence interval [CI], 0.02%-0.06%) from October 2005 to December 2008 with intracameral cefuroxime compared with a rate of 0.59% without cefuroxime, confirming the outcome of the ESCRS multicenter study. The efficacy of intracameral cefuroxime as a prophylactic measure against infectious endophthalmitis is now well established. It is not a perfect prophylactic because of limited efficacy against gram-negative bacteria. Cefuroxime is not available in prepackaged form for intracameral use; it has to be diluted from concentrate in the operating room, giving scope for errors in dilution and contamination. Cefuroxime is a second-generation cephalosporin from compounds that were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu.6 He noticed that these cultures produced substances that were effective against Salmonella typhi, the cause of typhoid fever, which had beta-lactamase. BetaQ 2010 ASCRS and ESCRS Published by Elsevier Inc.
lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotic agents such as penicillins, whereas cephalosporins are relatively resistant to beta-lactamase. Cefuroxime exerts antibacterial activity by inhibition of bacterial cell wall synthesis in susceptible species. In the ESCRS multicenter study,5 in the proven infective endophthalmitis cases, the absence of cefuroxime and the use of silicone intraocular lens (IOL) optic material and clear corneal incisions were significantly associated with an increased risk and there was evidence that men were more predisposed to infection. The absence of an intracameral cefuroxime prophylactic regimen at 1.0 mg in 0.1 mL normal saline was associated with a 4.92-fold increase (95% CI, 1.87-12.9) in the risk for total postoperative endophthalmitis. Is There a Downside to Intracameral Cefuroxime in Cataract Surgery? Is It Safe? A severe anaphylactic reaction has been reported 5 minutes after 1.0 mg of cefuroxime was injected into the anterior chamber after routine phacoemulsification and IOL implantation.7 The patient, who had a known allergy to penicillin, recovered well after immediate resuscitative action was taken, emphasizing the need for immediate availability of trained resuscitation staff in the operating room. However, immunoglobulin E-mediated allergy to cefuroxime is rare in the cataract population. Intracameral cefuroxime 1.0 mg appears safe in terms of local toxicity. It achieves high aqueous concentrations even 1 hour after surgery.8 What Happens to the Macula and Fovea During and After Cataract and IOL Implantation Surgery and Does Cefuroxime Have Any Effect? In a study of foveal and perifoveal thickness measured by optical coherence tomography after phacoemulsification and IOL implantation, the initial (preoperative) mean value of 234.1 G 2.6 (SEM) (n Z 536) in the 6.0 mm perifoveal region increased to 242.5 G 2.6 mm (n Z 488) (P!.01) at 1 week, 247.7 G 4.6 mm (n Z 352) (P!.01) at 1 month, and 246.0 G 5.9 mm (n Z 208) (P!.05) at 2 months. However, the relative change in macular thickness was moderated3.5%, 5.6%, and 5.3%, respectively. There was no reported correlation between macular thickening and visual acuity.9,10 Cefuroxime 1.0 mg intracameral use in a double-masked clinical study showed no significant difference in postoperative macular thickness.11 0886-3350/10/$dsee front matter doi:10.1016/j.jcrs.2009.12.013
191
192
FROM THE EDITOR
How Cost Effective Is the Use of Intracameral Cefuroxime in Preventing Endophthalmitis After Cataract Surgery? In a recently reported study, Sharifi et al.12 concluded that owing to their high costs, the many commonly used topical antibiotic agents are not cost effective compared with intracameral cefuroxime, even under optimistic assumptions about their efficacy. Efficacy was defined as the absolute reduction in rate of infection from background rate of infection, sourced from the ophthalmic literature. The most expensive topical fluoroquinolones studied, gatifloxacin and moxifloxacin, would have to be more than or equal to 19 times more effective than intracameral cefuroxime to achieve cost-effective equivalence.
3.
4.
5.
6. 7.
8.
What Has Been the Effect of the Positive Findings of the ESCRS Multicenter Trial of the Efficacy of Intracameral Cefuroxime in Cataract Surgery on Surgeon Protocols? The ESCRS endophthalmitis study published preliminary results in 200613 showing a near 5-fold decrease in the rates of postoperative endophthalmitis with the use of intracameral cefuroxime. The findings generated considerable controversy and 1 year later, its recommendations had been heeded by only 6% of ASCRS members.14 A United Kingdom survey sought to gauge the uptake among surgeons in the U.K. Fiftyfive percent of respondents were using intracameral cefuroxime; 48% had switched after publication of the ESCRS study. Of those remaining, 68% reported their main concern was the risk for dilution errors in the absence of a commercially preformulated preparation, with 67% stating they would switch if such a product became available.15 Emanuel Rosen, FRCSE
9.
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REFERENCES 1. Tervo T, Ljungberg P, Kautiainen T, Puska P, Lehto I, Raivio I, Ja¨rvinen E, Kuusela P, Tarkkanen A. Prospective evaluation of external ocular microbial growth and aqueous humor contamination during cataract surgery. J Cataract Refract Surg 1999; 25:65–71 2. Mistlberger A, Ruckhofer J, Raithel E, Mu¨ller M, Alzner E, Egger SF, Grabner G. Anterior chamber contamination during
15.
cataract surgery with intraocular lens implantation. J Cataract Refract Surg 1997; 23:1064–1069 Lee BJ, Smith SD, Jeng BH. Suture related corneal infections after clear corneal cataract surgery. J Cataract Refract Surg 2009; 35:939–942 Kelly SP, Ajit RR, Glenister HM. Hazards of redundant corneal sutures: a safety message [letter]. J Cataract Refract Surg 2004; 30:1151–1152 ESCRS Endophthalmitis Study Group. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg 2007; 33:978–988 Bo G. Giuseppe Brotzu and the discovery of cephalosporins. Clin Microbiol Infect 2000; 6(suppl 3):6–9 Villada JR, Vicente U, Javaloy J, Alio´ JL. Severe anaphylactic reaction after intracameral antibiotic administration during cataract surgery. J Cataract Refract Surg 2005; 31:620–621 Montan PG, Wejde G, Setterquist H, Rylander M, Zetterstro¨m C. Prophylactic intracameral cefuroxime; evaluation of safety and kinetics in cataract surgery. J Cataract Refract Surg 2002; 28:982–987 Biro Z, Balla Z, Kovacs B. Change of foveal and perifoveal thickness measured by OCT after phacoemulsification and IOL implantation. Eye 2008; 22:8–12. Available at: http:// www.nature.com/eye/journal/v22/n1/pdf/6702460a.pdf. Accessed November 21, 2009 von Jagow B, Ohrloff C, Kohnen T. Macular thickness after uneventful cataract surgery determined by optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2007; 245:1765–1771 Gupta MS, McKee HDR, Saldan˜a M, Stewart OG. Macular thickness after cataract surgery with intracameral cefuroxime. J Cataract Refract Surg 2005; 31:1163–1166 Sharifi E, Porco TC, Naseri A. Cost-effectiveness analysis of intracameral cefuroxime use for prophylaxis of endophthalmitis after cataract surgery. Ophthalmology 2009; 116:1887–1896 Barry P, Seal DV, Gettinby G, Lees F, Peterson M, Revie CW. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; preliminary report of principal results from a European multicenter study; the ESCRS Endophthalmitis Study Group. J Cataract Refract Surg 2006; 32:407–410 Chang DF, Braga-Mele R, Mamalis N, Masket S, Miller KM, Nichamin LD, Packard RB, Packer M. Prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2007 ASCRS member survey; the ASCRS Cataract Clinical Committee. J Cataract Refract Surg 2007; 33:1801– 1805 Gore DM, Angunawela RI, Little BC. United Kingdom survey of antibiotic prophylaxis practice after publication of the ESCRS Endophthalmitis Study. J Cataract Refract Surg 2009; 35:770– 773
J CATARACT REFRACT SURG - VOL 36, FEBRUARY 2010