- Email: [email protected]
Incidence of endophthalmitis and impact of prophylaxis with cefuroxime on cataract surgery
ARTICLE
Incidence of endophthalmitis and impact of prophylaxis with cefuroxime on cataract surgery Gil Rodríguez-Caravaca, MD, PhD, MPH, Ma Carmen García-Saenz, MD, PhD, Ma Concepci on Villar-del-Campo, MD, PhD, Yolanda Andres-Alba, MD, Alfonso Arias-Puente, MD, PhD
PURPOSE: To evaluate the clinical and economic impact of prophylactic administration of intracameral cefuroxime on cataract surgery. SETTING: Hospital Universitario Fundacion Alcorcon, Madrid, Spain. DESIGN: Quasi-experimental study with before and after analysis. METHODS: The evolution of the cumulative incidence of endophthalmitis before and after (October 2005) administration of intracameral cefuroxime as endophthalmitis prophylaxis in cataract surgery was studied. The annual incidence adjusting to a Poisson distribution was compared. The effectiveness of the prophylaxis was evaluated with the relative risk (RR). The impact of cefuroxime was evaluated with the attributable risk fraction and the number of patients needed to treat to avoid a case of endophthalmitis. RESULTS: Cataract surgery was performed in 19 463 patients, 6595 patients before and 12 868 patients after October 2005. Endophthalmitis was diagnosed in 44 cases (39 before and 5 after). Positive microbiology cultures were obtained in 29 patients (66%). The overall cumulative incidence was 0.23 cases per 100 patients. Cefuroxime protected against endophthalmitis (RR Z 0.06; P<.05; 95% confidence interval [CI], 0.03-0.17); the impact or number needed to treat was 182, and the attributable risk fraction was 0.93% (P<.05; 95% CI, 0.82 to 0.97). The cost of a dose of cefuroxime was V1, and the cost of a case of endophthalmitis was V1358. The potential saving with cefuroxime was V1177 for every 182 patients treated. CONCLUSION: Intracameral cefuroxime reduced the incidence of endophthalmitis in cataract surgery and had a high clinical and economic impact on its prevention. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2013; 39:1399–1403 Q 2013 ASCRS and ESCRS
Cataract extraction is the most common ophthalmologic surgery. Postoperative complications of this type of surgery are varied, and endophthalmitis is the most severe and most feared by ophthalmologists. In the majority of cases, endophthalmitis appears unexpectedly and can lead to vision loss.1 The incidence of postoperative endophthalmitis varies between 0.01% and 1.0%.2 Although the diagnosis and treatment of this disease has improved greatly, all possible effort should be made to reduce its incidence. Several factors, such as age, intraoperative complications, and type of surgical incision,3 can influence its onset. Among the factors that appear to have the most Q 2013 ASCRS and ESCRS Published by Elsevier Inc.
influence on ocular infection is the type of antibiotic prophylaxis and its route of administration.4 Intracameral cefuroxime has been shown to be effective in preventing ocular infection after cataract surgery and in reducing the incidence of ocular infection in this type of surgery.5 In Spain, we do not have a centralized registry of the incidence of endophthalmitis and published epidemiologic studies in the incidence of this disease are scarce and local, with the majority being retrospective.6 There are registries in countries in our region that monitor the incidence of this disease and provide sufficient understanding of its magnitude.7,8 With 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2013.03.031
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these registries, we can perform clinical follow-up and an epidemiologic study of cases of postoperative endophthalmitis. When Hospital Universitario Fundacion Alcorcon opened in 1998, we designed a registry of incident cases of postoperative endophthalmitis in patients who had cataract surgery. Intracameral prophylaxis with cefuroxime was instituted in 2005 for cataract surgery to reduce the incidence of endophthalmitis. The purpose of this study was to describe the evolution of the incidence of postoperative endophthalmitis from 1998 to 2012 and to evaluate the clinical and economic impact of introducing intracameral cefuroxime administration as antibiotic prophylaxis and a preventive measure for endophthalmitis after cataract surgery. PATIENTS AND METHODS This quasi-experimental study included before-and-after analysis to compare the incidence of endophthalmitis after administration of 2 antibiotic prophylaxis regimens before cataract surgery during 2 consecutive time periods. The study was performed between January 1999 and December 2012. The study was approved by the hospital's Ethics and Research Committee, and all patients signed an informed consent form. Patients who had cataract surgery with intraocular lens (IOL) placement at Hospital Universitario Fundacion Alcorcon were included and divided into 2 groups according to the antibiotic prophylaxis regimen. The common antiseptic protocol for all patients included povidone–iodine 10.0% on the skin and povidone–iodine 5.0% placed in the conjunctival sac (or chlorhexidine 0.05% in allergic patients) for 5 minutes before surgery. The surgeon checked the right time of application of the antiseptic and then covered the patient with an adhesive ophthalmic drape. The before group was made up of patients who had surgery before October 2005 who received postoperative topical ofloxacin 0.3% drops and dexamethasone 0.1% drops. In the case of retrobulbar anesthesia, a subconjunctival aminoglycoside Submitted: February 8, 2013. Final revision submitted: March 16, 2013. Accepted: March 18, 2013. From the Preventive Medicine Unit (Rodrıguez-Caravaca), Hospital Universitario Fundacion Alcorcon, the Department of Preventive Medicine and Public Health (Rodrıguez-Caravaca) and Department of Medicine and Surgery (Arias-Puente), Universidad Rey Juan Carlos, Alcorcon, the Ophthalmology Unit (Garcıa-Saenz, Andres-Alba, Arias-Puente), Hospital Universitario Fundacion Alcorcon, and the Department of Medicine (Villar-del-Campo), Universidad Complutense, Madrid, Spain. Guillermo Lopez Calderon, Montserrat Perez Encinas, and Silvia del Riego Sayalero helped with the cost analysis in this work. Corresponding author: Gil Rodrıguez-Caravaca, MD, PhD, MPH, Preventive Medicine Unit, Hospital Universitario Fundaci on Alcorcon, C/Budapest, 1, 28922 Alcorcon, Madrid, Spain. E-mail: [email protected].
(20 mg gentamicin) was added. The after group consisted of patients who had surgery from October 2005 to December 2012 who, in addition to the previous regimen, were administered intracameral cefuroxime in a slow injection just at the end of the surgery at a dosage of 1 mg/0.1 mL (or vancomycin 1 mg/0.1 mL in patients who were allergic). Endophthalmitis was considered to be present in patients with compatible signs and symptoms for which other causes of intraocular inflammation, such as toxic anterior segment syndrome or noninfectious uveitis, had been ruled out. The follow-up of all cases of endophthalmitis was at least 12 months. All cases were patients who presented back to the hospital. The signs and symptoms of endophthalmitis are pain, palpebral edema, conjunctival chemosis, hypopyon, turbidity of the anterior chamber and vitreous, and loss of vision. All patients in whom there was a clinical suspicion of endophthalmitis had samples collected from the aqueous and vitreous humor for microbiology study. The final diagnosis was always made by an expert ophthalmologist. Patients were followed clinically after the intervention, and the diagnosis of infection was set according to the Centers for Disease Control/National Healthcare Safety Network surveillance definitions of health care–associated infections.9 The variables studied included sex, age, microorganism, study group (before group and after group), administration of antibiotic prophylaxis, the surgeon, and the presence of infection. The cost of a dose of cefuroxime and the hospital costs of a case of endophthalmitis were calculated with full-cost analysis of analytic accounting, taking into account all hospital expenses of each case of endophthalmitis with all the expenses. The cumulative incidence of endophthalmitis was studied and evaluated on a continuous and prospective basis throughout the study period. The incidence of endophthalmitis was evaluated and its temporal tendency adjusted with a Poisson distribution; using this, the annual probability of cases of endophthalmitis was calculated. The qualitative variables were described with frequency distributions and compared using the chi-square or Fisher exact test when the application criteria were not met. The quantitative variables were described as the mean G SD and compared using the Student t test. The relative risk (RR) of infection was calculated by comparing the incidence of infection before and after October 2005 in each group. The absolute difference in the risk or the difference between the incidence of infection in those treated with cefuroxime and those not treated (attributable risk), the absolute reduction in the risk or the percentage of risk reduction, the attributable fraction or relative difference in risk, the RR reduction, and the impact of the use of prophylaxis with cefuroxime (defined as the number of patients needed to treat to avoid an addition infection versus the incidence before 2005) were calculated. Statistical significance was defined as a P value less than 0.05. Statistical analysis was performed using SPSS software (version 19.0., SPSS, Inc.).
RESULTS This study evaluated 19 463 patients who had surgery for cataract. Of the patients, 8369 (43%) were men and 11094 (57%) were women (P!.05). The before group without prophylaxis with cefuroxime comprised 6595 patients, and the after group with prophylaxis with cefuroxime comprised 12 868 patients. No patient refused to participate.
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Figure 1. Number of cases and microorganisms responsible for endophthalmitis (N Z 44).
Figure 2. Evolution of the incidence of endophthalmitis and comparison before and after 2005 (P!.05).
Forty-four cases of postoperative endophthalmitis (39 before and 5 after) were diagnosed, 19 in men and 25 in women (PO.05). The mean age of the men who had surgery was 71.2 years G 7.3 (SD) and the mean age of the women, 80.4 G 8.5 years (P!.05). Positive microbiology cultures from the aqueous or vitreous humor were obtained in 29 patients (65.9%). The most commonly isolated microorganisms were coagulase-negative Staphylococcus (CoNS) species (38.6%) and Staphylococcus aureus (16.6%) (Figure 1). Patients were operated on by 1 of 15 attending surgeons; no association was found between infected patients and the treating physician (P!.05). The overall cumulative incidence of endophthalmitis was 0.23 cases per 100 patients. The continuous progress of the annual cumulative incidence showed a stable trend that had decreased since 2005 (Figure 2) after the introduction of intracameral prophylaxis with cefuroxime (P!.05). The RR of prophylaxis with cefuroxime or risk for developing endophthalmitis when treated with cefuroxime was very low (RR Z 0.06; P!.05; 95% confidence interval [CI], 0.03-0.17). The impact or number of patients needed to treat to avoid an additional infection was 182, and the
attributable risk fraction or difference in the RR was 0.93% (P!.05; 95% CI, 0.82 to 0.97). Table 1 shows the impact and effect measures with their significance and 95% CI. Analysis using analytic accounting of the cost of a dose of cefuroxime was V1.0. The cost of a case of endophthalmitis, taking into account all the hospital costs, was V1358.7. The potential savings was V1176.7 for every 182 patients treated prophylactically with intracameral cefuroxime.
Table 1. Effect and impact indices of prophylaxis with cefuroxime. Index Relative risk Absolute difference in risk (AR) (%) Absolute risk reduction (%) Difference in relative risk (AF) (%) Relative risk reduction
Estimation
95% CI 0.17 0.61
P Value !.05 !.05
0.06 0.55
0.03, 0.49,
0.55
0.46, 0.61
!.05
0.93
0.82,
!.05
0.93
0.82, 0.97
0.97
!.05
AF Z attributable risk fraction; AR Z attributable risk; CI Z confidence interval
DISCUSSION Endophthalmitis is a very severe complication10,11 that can be caused by various factors, and its most common clinical presentation is the acute form after cataract surgery.12 It is important to evaluate the incidence of endophthalmitis to understand the true magnitude of the problem. According to studies published in recent decades,2,6,13 the incidence varies between 0.01% and 1.0%. We implemented a prospective evaluation plan for the incidence of endophthalmitis in cataract surgery from the moment our hospital opened in 1998. Analysis of the evolution of our infection rates, according to data reported previously, showed a stable incidence of endophthalmitis that was relatively high until 2005,14 when it decreased significantly after a change in the prophylaxis regimen in October of that year. Other factors related to antisepsis or the phacoemulsification technique may have influenced the final rate of endophthalmitis; these factors include surgical experience, smaller incisions, and the use of injected IOLs instead of foldable IOLs, the latter of which could have more contact with the periocular area. However, no substantial changes were made before that timepoint except for the introduction of cefuroxime. Since then, the incidence of endophthalmitis has gradually decreased; our current incidence is one of the lowest reported.10–13 In addition, the robustness of our prospective cohort study should be highlighted;
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our design provides a high level of scientific evidence and ours is one of the largest prospective studies of endophthalmitis published in Spain.6,15,16 One of the most useful strategies for preventing endophthalmitis is the use of prophylactic antibiotics, and there is evidence supporting the efficacy of using intracameral cefuroxime5,17 and its cost effectiveness.18 Swedish ophthalmologists began using cefuroxime prophylaxis on a routine basis starting in 2002 with very good results.7,19 The multicenter European Society of Cataract & Refractive Surgeons study confirmed the Swedish experience and found a reduction in the incidence of endophthalmitis, down to rates as low as 0.05%, after an injection of cefuroxime at the end of cataract surgery.5,20 The study also considered the suitability of coverage of cefuroxime against the majority of microorganisms that cause endophthalmitis in our region, which include CoNS, S aureus, and other gram-negative bacteria to a lesser extent. There is also evidence of the usefulness of cefuroxime as a prophylactic antibiotic for this flora in surgical procedures other then cataract extraction.21,22 After prospective evaluation of the incidence of endophthalmitis since the prophylactic introduction of intracameral cefuroxime, we found a decrease in the risk for infection compared with the risk using the previous prophylactic regimen, with a significantly lower incidence of endophthalmitis in patients treated with cefuroxime (RR Z 0.06; P!.05). Another study16 also found a decrease in the incidence of endophthalmitis in cataract surgery after administration of intracameral prophylaxis with cephalosporins other than cefuroxime, such as cephazolin. Given that the RR is independent of the incidence, we calculated the attributable risk or difference in incidences between those treated with cefuroxime and those who did not receive cefuroxime. The attributable risk was 0.55%, and its negative sign indicates a decrease in the risk or a preventative or protective effect of cefuroxime. Therefore, for every 1000 patients treated with cefuroxime, 5.4 fewer cases of endophthalmitis resulted (absolute risk reduction 0.55%). The attributable fraction for cefuroxime, which estimates the proportion of disease avoided by is use, was also calculated by taking into account the baseline incidence in patients not exposed to the antibiotic. We obtained an attributable fraction of 93%, which represents a reduction in the RR of 92.8%, meaning a reduction in the risk for endophthalmitis of 93% in patients treated with cefuroxime versus those treated with the previous prophylaxis regimen. This reduction led to the prevention of 1 case of endophthalmitis for every 182 patients treated with cefuroxime (number of patients needed to treat Z 182), with the subsequent economic savings to the hospital of V1176.70 for every
182 patients who were administered cefuroxime. One should also consider the intangible savings of avoiding patient suffering and disability (sometimes blindness), although these expenses and other out-ofhospital expenses (eg, losing work, lost working hours) were not calculated. The majority of microorganisms isolated in the cultures from infected patients corresponded to the saprophytic conjunctival flora of healthy individuals and the flora described in other studies.6,15,17 We do not know the effect of environmental factors (eg, hygiene, asepsis) on the cases of disease that were not prevented by cefuroxime because we did not evaluate them. However, we have protocols for cleaning, disinfecting, and sterilizing the operating room, environment, and the surgical material used to minimize this effect. The surgical technique and the technical conditions in the operating rooms did not change substantially during the study, and selection bias was controlled for by including all cataract interventions in the study. In addition, the quasiexperimental design with before and after analysis provided a high level of scientific evidence even though the patients were not randomized. This gives robustness to our work compared with many studies with a retrospective design. We conclude that intracameral administration of cefuroxime in the prevention of endophthalmitis after cataract surgery seems effective and may contribute to the reduction in the incidence of endophthalmitis and, therefore, to cost reductions by preventing cases of endophthalmitis. This is 1 more prophylaxis alternative, and its impact, antibiotic spectrum, and cost effectiveness should be taken into account. WHAT WAS KNOWN Endophthalmitis is a severe complication of cataract surgery, and its incidence has been decreasing for the past decade. Studies of the incidence of endophthalmitis are common; however, most are retrospective. Intracameral cefuroxime has been shown to be effective in preventing ocular infection after cataract surgery and to be cost effective. WHAT THIS PAPER ADDS Intracameral cefuroxime reduced the incidence of endophthalmitis significantly since its introduction. It had a high clinical and economical impact; it prevented a case of endophthalmitis for every 182 patients who were administered prophylaxis.
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REFERENCES 1. Eifrig CWG, Flynn HW Jr, Scott IU, Newton J. Acute-onset postoperative endophthalmitis: review of incidence and visual outcomes (1995–2001). Ophthalmic Surg Lasers 2002; 33: 373–378; erratum, 2003; 34:80 2. Taban M, Behrens A, Newcomb RL, Nobe MY, Saedi G, Sweet PM, McDonnell PJ. Acute endophthalmitis following cataract surgery; a systematic review of the literature. Arch Ophthalmol 2005; 123:613–620. Available at: http://archopht. jamanetwork.com/data/Journals/OPHTH/9940/ecs40117.pdf. Accessed April 4, 2013 €m M, Wejde G, Stenevi U, Thorburn W, Molntan P. En3. Lundstro dophthalmitis after cataract surgery; a nationwide prospective study evaluating incidence in relation to incision type and location. Ophthalmology 2007; 114:866–870 4. Cochereau I, Korobelnik J-F, Robert P-Y, Hajjar J. Antibiopro propos des recomphylaxie en chirurgie ophtalmologique. A mandations de l’AFSSAPS [Antibioprophylaxis in ocular surgery. AFSSAPS recommendations]. J Fr Ophtalmol 2011; 34:428–430 5. Barry P, Seal DV, Gettinby G, Lees F, Peterson M, Revie CW; ESCRS Endophthalmitis Study Group. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; preliminary report of principal results from a European multicenter study. J Cataract Refract Surg 2006; 32:407–410; erratum, 709 6. Duch A, Hurtado M, Lopez-Corell P, Diaz M, Menezo JL, Harto MA. Endoftalmitis postquirugicas. I: estudio retrospective ~os de endoftalmitis post-cirugia de cataractas [Postopde 12 an erative endophthalmitis. I: a 12-year retrospective study of endophthalmitis following cataract surgery]. Arch Soc Esp Oftalmol 1993; 65:317–324 € m M, Stenevi U, Thorburn W. En7. Wejde G, Montan P, Lundstro dophthalmitis following cataract surgery in Sweden: national Prospective Survey 1999–2001. Acta Ophthalmol Scand 2005; 83:7–10. Available at: http://www3.interscience.wiley.com/cgibin/fulltext/120092610/PDFSTART. Accessed April 4, 2013 8. Kodjikian L, Salvanet-Bouccara A, Grillon S, Forestier F, Seegmuller J-L, Berdeaux G; French Collaborative Study Group on Endophthalmitis. Postcataract acute endophthalmitis in France: national prospective survey. J Cataract Refract Surg 2009; 35:89–97 9. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care–associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36:309–332 n A. oculares asociadas a los 10. Casaroli-Marano RP, Ada implantes oculares [Eye infections associated with ocular implants]. Enferm Infecc Microbiol Clin 2008; 26:581–588. Available at: http://apps.elsevier.es/watermark/ctl_servlet?_fZ10& pident_articuloZ13128276&pident_usuarioZ0&pcontactidZ &pident_revistaZ28&tyZ93&accionZL&origenZelsevier& webZwww.elsevier.es&;lanZes&ficheroZ28v26n09a131282 76pdf001.pdf. Accessed April 4, 2013 11. Lalitha P, Rajagopalan J, Prakash K, Ramasamy K, Prajna NV, Srinivasan M. Postcataract endophthalmitis in South India; incidence and outcome. Ophthalmology 2005; 112:1885–1890
12. Altan T, Acar N, Kapran Z, Unver YB, Yurttaser S, € c‚u €ksu € mer Y, Eser I. Acute-onset endophthalmitis after cataKu ract surgery; success of initial therapy, visual outcomes, and related factors. Retina 2009; 29:606–612 13. Miller JJ, Scott IU, Flynn HW Jr, Smiddy WE, Newton J, Miller D. Acute-onset endophthalmitis after cataract surgery (2000– 2004): incidence, clinical settings, and visual acuity outcomes after treatment. Am J Ophthalmol 2005; 139:983–987 enz MC, Arias-Puente A, Rodrıguez-Caravaca G, 14. Garcıa-Sa ~uelos JB. Effectiveness of intracameral cefuroxime in Ban preventing endophthalmitis after cataract surgery; ten-year comparative study. J Cataract Refract Surg 2010; 36:203–207 15. Hurtado M, Duch AM, Mengual E, Menezo JL, Harto MA. Endof~os de talmitis postquirugicas. II: estudio retrospective de 12 an endoftalmitis post-cirugia no cristaliniana [Postoperative endophthalmitis. II: a 12-year retrospective study of endophthalmitis following non-crystalline surgery]. Arch Soc Esp Oftalmol 1993; 65:309–316 ndez-Marin I, Salvat-Serra M, Ferna ndez16. Romero-Aroca P, Me Ballart J, Almena-Garcia M, Reyes-Torres J. Results at seven years after the use of intracamerular cefazolin as an endophthalmitis prophylaxis in cataract surgery. BMC Ophthalmol 2012; 12:2. Available at: http://www.biomedcentral.com/content/pdf/ 1471-2415-12-2.pdf. Accessed April 4, 2013 17. Lockington D, Flowers H, Young D, Yorston D. Assessing the accuracy of intracameral antibiotic preparation for use in cataract surgery. J Cataract Refract Surg 2010; 36:286–289 18. 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 19. Montan PG, Wejde G, Koranyi G, Rylander M. Prophylactic intracameral cefuroxime; efficacy in preventing endophthalmitis after cataract surgery. J Cataract Refract Surg 2002; 28:977– 981 20. Bohigian GM. ESCRS study of endophthalmitis prophylaxis [letter]. J Cataract Refract Surg 2006; 32:1406–1407; reply by P Barry, 1407 €la € H. Comparison of vancomycin 21. Vuorisalo S, Pokela R, Syrja and cefuroxime for infection prophylaxis in coronary artery bypass surgery. Infect Control Hosp Epidemiol 1998; 19:234–239 22. Iribarren O, Araujo M. Effect of antimicrobial prophylaxis on the incidence of infections in clean surgical wounds in hospitals undergoing renovation. Infect Control Hosp Epidemiol 2006; 27:1372–1376. Available at: http://www.jstor.org/stable/ pdfplus/10.1086/509850.pdf. Accessed April 4, 2013
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First author: Gil Rodríguez-Caravaca, MD, PhD, MPH Preventive Medicine Unit, Hospital Universitario Fundacion Alcorcon, Madrid, Spain
Incidence of endophthalmitis and impact of prophylaxis with cefuroxime on cataract surgery Gil Rodríguez-Caravaca, MD, PhD, MPH, Ma Carmen García-Saenz, MD, PhD, Ma Concepci on Villar-del-Campo, MD, PhD, Yolanda Andres-Alba, MD, Alfonso Arias-Puente, MD, PhD
PURPOSE: To evaluate the clinical and economic impact of prophylactic administration of intracameral cefuroxime on cataract surgery. SETTING: Hospital Universitario Fundacion Alcorcon, Madrid, Spain. DESIGN: Quasi-experimental study with before and after analysis. METHODS: The evolution of the cumulative incidence of endophthalmitis before and after (October 2005) administration of intracameral cefuroxime as endophthalmitis prophylaxis in cataract surgery was studied. The annual incidence adjusting to a Poisson distribution was compared. The effectiveness of the prophylaxis was evaluated with the relative risk (RR). The impact of cefuroxime was evaluated with the attributable risk fraction and the number of patients needed to treat to avoid a case of endophthalmitis. RESULTS: Cataract surgery was performed in 19 463 patients, 6595 patients before and 12 868 patients after October 2005. Endophthalmitis was diagnosed in 44 cases (39 before and 5 after). Positive microbiology cultures were obtained in 29 patients (66%). The overall cumulative incidence was 0.23 cases per 100 patients. Cefuroxime protected against endophthalmitis (RR Z 0.06; P<.05; 95% confidence interval [CI], 0.03-0.17); the impact or number needed to treat was 182, and the attributable risk fraction was 0.93% (P<.05; 95% CI, 0.82 to 0.97). The cost of a dose of cefuroxime was V1, and the cost of a case of endophthalmitis was V1358. The potential saving with cefuroxime was V1177 for every 182 patients treated. CONCLUSION: Intracameral cefuroxime reduced the incidence of endophthalmitis in cataract surgery and had a high clinical and economic impact on its prevention. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2013; 39:1399–1403 Q 2013 ASCRS and ESCRS
Cataract extraction is the most common ophthalmologic surgery. Postoperative complications of this type of surgery are varied, and endophthalmitis is the most severe and most feared by ophthalmologists. In the majority of cases, endophthalmitis appears unexpectedly and can lead to vision loss.1 The incidence of postoperative endophthalmitis varies between 0.01% and 1.0%.2 Although the diagnosis and treatment of this disease has improved greatly, all possible effort should be made to reduce its incidence. Several factors, such as age, intraoperative complications, and type of surgical incision,3 can influence its onset. Among the factors that appear to have the most Q 2013 ASCRS and ESCRS Published by Elsevier Inc.
influence on ocular infection is the type of antibiotic prophylaxis and its route of administration.4 Intracameral cefuroxime has been shown to be effective in preventing ocular infection after cataract surgery and in reducing the incidence of ocular infection in this type of surgery.5 In Spain, we do not have a centralized registry of the incidence of endophthalmitis and published epidemiologic studies in the incidence of this disease are scarce and local, with the majority being retrospective.6 There are registries in countries in our region that monitor the incidence of this disease and provide sufficient understanding of its magnitude.7,8 With 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2013.03.031
1399
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these registries, we can perform clinical follow-up and an epidemiologic study of cases of postoperative endophthalmitis. When Hospital Universitario Fundacion Alcorcon opened in 1998, we designed a registry of incident cases of postoperative endophthalmitis in patients who had cataract surgery. Intracameral prophylaxis with cefuroxime was instituted in 2005 for cataract surgery to reduce the incidence of endophthalmitis. The purpose of this study was to describe the evolution of the incidence of postoperative endophthalmitis from 1998 to 2012 and to evaluate the clinical and economic impact of introducing intracameral cefuroxime administration as antibiotic prophylaxis and a preventive measure for endophthalmitis after cataract surgery. PATIENTS AND METHODS This quasi-experimental study included before-and-after analysis to compare the incidence of endophthalmitis after administration of 2 antibiotic prophylaxis regimens before cataract surgery during 2 consecutive time periods. The study was performed between January 1999 and December 2012. The study was approved by the hospital's Ethics and Research Committee, and all patients signed an informed consent form. Patients who had cataract surgery with intraocular lens (IOL) placement at Hospital Universitario Fundacion Alcorcon were included and divided into 2 groups according to the antibiotic prophylaxis regimen. The common antiseptic protocol for all patients included povidone–iodine 10.0% on the skin and povidone–iodine 5.0% placed in the conjunctival sac (or chlorhexidine 0.05% in allergic patients) for 5 minutes before surgery. The surgeon checked the right time of application of the antiseptic and then covered the patient with an adhesive ophthalmic drape. The before group was made up of patients who had surgery before October 2005 who received postoperative topical ofloxacin 0.3% drops and dexamethasone 0.1% drops. In the case of retrobulbar anesthesia, a subconjunctival aminoglycoside Submitted: February 8, 2013. Final revision submitted: March 16, 2013. Accepted: March 18, 2013. From the Preventive Medicine Unit (Rodrıguez-Caravaca), Hospital Universitario Fundacion Alcorcon, the Department of Preventive Medicine and Public Health (Rodrıguez-Caravaca) and Department of Medicine and Surgery (Arias-Puente), Universidad Rey Juan Carlos, Alcorcon, the Ophthalmology Unit (Garcıa-Saenz, Andres-Alba, Arias-Puente), Hospital Universitario Fundacion Alcorcon, and the Department of Medicine (Villar-del-Campo), Universidad Complutense, Madrid, Spain. Guillermo Lopez Calderon, Montserrat Perez Encinas, and Silvia del Riego Sayalero helped with the cost analysis in this work. Corresponding author: Gil Rodrıguez-Caravaca, MD, PhD, MPH, Preventive Medicine Unit, Hospital Universitario Fundaci on Alcorcon, C/Budapest, 1, 28922 Alcorcon, Madrid, Spain. E-mail: [email protected].
(20 mg gentamicin) was added. The after group consisted of patients who had surgery from October 2005 to December 2012 who, in addition to the previous regimen, were administered intracameral cefuroxime in a slow injection just at the end of the surgery at a dosage of 1 mg/0.1 mL (or vancomycin 1 mg/0.1 mL in patients who were allergic). Endophthalmitis was considered to be present in patients with compatible signs and symptoms for which other causes of intraocular inflammation, such as toxic anterior segment syndrome or noninfectious uveitis, had been ruled out. The follow-up of all cases of endophthalmitis was at least 12 months. All cases were patients who presented back to the hospital. The signs and symptoms of endophthalmitis are pain, palpebral edema, conjunctival chemosis, hypopyon, turbidity of the anterior chamber and vitreous, and loss of vision. All patients in whom there was a clinical suspicion of endophthalmitis had samples collected from the aqueous and vitreous humor for microbiology study. The final diagnosis was always made by an expert ophthalmologist. Patients were followed clinically after the intervention, and the diagnosis of infection was set according to the Centers for Disease Control/National Healthcare Safety Network surveillance definitions of health care–associated infections.9 The variables studied included sex, age, microorganism, study group (before group and after group), administration of antibiotic prophylaxis, the surgeon, and the presence of infection. The cost of a dose of cefuroxime and the hospital costs of a case of endophthalmitis were calculated with full-cost analysis of analytic accounting, taking into account all hospital expenses of each case of endophthalmitis with all the expenses. The cumulative incidence of endophthalmitis was studied and evaluated on a continuous and prospective basis throughout the study period. The incidence of endophthalmitis was evaluated and its temporal tendency adjusted with a Poisson distribution; using this, the annual probability of cases of endophthalmitis was calculated. The qualitative variables were described with frequency distributions and compared using the chi-square or Fisher exact test when the application criteria were not met. The quantitative variables were described as the mean G SD and compared using the Student t test. The relative risk (RR) of infection was calculated by comparing the incidence of infection before and after October 2005 in each group. The absolute difference in the risk or the difference between the incidence of infection in those treated with cefuroxime and those not treated (attributable risk), the absolute reduction in the risk or the percentage of risk reduction, the attributable fraction or relative difference in risk, the RR reduction, and the impact of the use of prophylaxis with cefuroxime (defined as the number of patients needed to treat to avoid an addition infection versus the incidence before 2005) were calculated. Statistical significance was defined as a P value less than 0.05. Statistical analysis was performed using SPSS software (version 19.0., SPSS, Inc.).
RESULTS This study evaluated 19 463 patients who had surgery for cataract. Of the patients, 8369 (43%) were men and 11094 (57%) were women (P!.05). The before group without prophylaxis with cefuroxime comprised 6595 patients, and the after group with prophylaxis with cefuroxime comprised 12 868 patients. No patient refused to participate.
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Figure 1. Number of cases and microorganisms responsible for endophthalmitis (N Z 44).
Figure 2. Evolution of the incidence of endophthalmitis and comparison before and after 2005 (P!.05).
Forty-four cases of postoperative endophthalmitis (39 before and 5 after) were diagnosed, 19 in men and 25 in women (PO.05). The mean age of the men who had surgery was 71.2 years G 7.3 (SD) and the mean age of the women, 80.4 G 8.5 years (P!.05). Positive microbiology cultures from the aqueous or vitreous humor were obtained in 29 patients (65.9%). The most commonly isolated microorganisms were coagulase-negative Staphylococcus (CoNS) species (38.6%) and Staphylococcus aureus (16.6%) (Figure 1). Patients were operated on by 1 of 15 attending surgeons; no association was found between infected patients and the treating physician (P!.05). The overall cumulative incidence of endophthalmitis was 0.23 cases per 100 patients. The continuous progress of the annual cumulative incidence showed a stable trend that had decreased since 2005 (Figure 2) after the introduction of intracameral prophylaxis with cefuroxime (P!.05). The RR of prophylaxis with cefuroxime or risk for developing endophthalmitis when treated with cefuroxime was very low (RR Z 0.06; P!.05; 95% confidence interval [CI], 0.03-0.17). The impact or number of patients needed to treat to avoid an additional infection was 182, and the
attributable risk fraction or difference in the RR was 0.93% (P!.05; 95% CI, 0.82 to 0.97). Table 1 shows the impact and effect measures with their significance and 95% CI. Analysis using analytic accounting of the cost of a dose of cefuroxime was V1.0. The cost of a case of endophthalmitis, taking into account all the hospital costs, was V1358.7. The potential savings was V1176.7 for every 182 patients treated prophylactically with intracameral cefuroxime.
Table 1. Effect and impact indices of prophylaxis with cefuroxime. Index Relative risk Absolute difference in risk (AR) (%) Absolute risk reduction (%) Difference in relative risk (AF) (%) Relative risk reduction
Estimation
95% CI 0.17 0.61
P Value !.05 !.05
0.06 0.55
0.03, 0.49,
0.55
0.46, 0.61
!.05
0.93
0.82,
!.05
0.93
0.82, 0.97
0.97
!.05
AF Z attributable risk fraction; AR Z attributable risk; CI Z confidence interval
DISCUSSION Endophthalmitis is a very severe complication10,11 that can be caused by various factors, and its most common clinical presentation is the acute form after cataract surgery.12 It is important to evaluate the incidence of endophthalmitis to understand the true magnitude of the problem. According to studies published in recent decades,2,6,13 the incidence varies between 0.01% and 1.0%. We implemented a prospective evaluation plan for the incidence of endophthalmitis in cataract surgery from the moment our hospital opened in 1998. Analysis of the evolution of our infection rates, according to data reported previously, showed a stable incidence of endophthalmitis that was relatively high until 2005,14 when it decreased significantly after a change in the prophylaxis regimen in October of that year. Other factors related to antisepsis or the phacoemulsification technique may have influenced the final rate of endophthalmitis; these factors include surgical experience, smaller incisions, and the use of injected IOLs instead of foldable IOLs, the latter of which could have more contact with the periocular area. However, no substantial changes were made before that timepoint except for the introduction of cefuroxime. Since then, the incidence of endophthalmitis has gradually decreased; our current incidence is one of the lowest reported.10–13 In addition, the robustness of our prospective cohort study should be highlighted;
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our design provides a high level of scientific evidence and ours is one of the largest prospective studies of endophthalmitis published in Spain.6,15,16 One of the most useful strategies for preventing endophthalmitis is the use of prophylactic antibiotics, and there is evidence supporting the efficacy of using intracameral cefuroxime5,17 and its cost effectiveness.18 Swedish ophthalmologists began using cefuroxime prophylaxis on a routine basis starting in 2002 with very good results.7,19 The multicenter European Society of Cataract & Refractive Surgeons study confirmed the Swedish experience and found a reduction in the incidence of endophthalmitis, down to rates as low as 0.05%, after an injection of cefuroxime at the end of cataract surgery.5,20 The study also considered the suitability of coverage of cefuroxime against the majority of microorganisms that cause endophthalmitis in our region, which include CoNS, S aureus, and other gram-negative bacteria to a lesser extent. There is also evidence of the usefulness of cefuroxime as a prophylactic antibiotic for this flora in surgical procedures other then cataract extraction.21,22 After prospective evaluation of the incidence of endophthalmitis since the prophylactic introduction of intracameral cefuroxime, we found a decrease in the risk for infection compared with the risk using the previous prophylactic regimen, with a significantly lower incidence of endophthalmitis in patients treated with cefuroxime (RR Z 0.06; P!.05). Another study16 also found a decrease in the incidence of endophthalmitis in cataract surgery after administration of intracameral prophylaxis with cephalosporins other than cefuroxime, such as cephazolin. Given that the RR is independent of the incidence, we calculated the attributable risk or difference in incidences between those treated with cefuroxime and those who did not receive cefuroxime. The attributable risk was 0.55%, and its negative sign indicates a decrease in the risk or a preventative or protective effect of cefuroxime. Therefore, for every 1000 patients treated with cefuroxime, 5.4 fewer cases of endophthalmitis resulted (absolute risk reduction 0.55%). The attributable fraction for cefuroxime, which estimates the proportion of disease avoided by is use, was also calculated by taking into account the baseline incidence in patients not exposed to the antibiotic. We obtained an attributable fraction of 93%, which represents a reduction in the RR of 92.8%, meaning a reduction in the risk for endophthalmitis of 93% in patients treated with cefuroxime versus those treated with the previous prophylaxis regimen. This reduction led to the prevention of 1 case of endophthalmitis for every 182 patients treated with cefuroxime (number of patients needed to treat Z 182), with the subsequent economic savings to the hospital of V1176.70 for every
182 patients who were administered cefuroxime. One should also consider the intangible savings of avoiding patient suffering and disability (sometimes blindness), although these expenses and other out-ofhospital expenses (eg, losing work, lost working hours) were not calculated. The majority of microorganisms isolated in the cultures from infected patients corresponded to the saprophytic conjunctival flora of healthy individuals and the flora described in other studies.6,15,17 We do not know the effect of environmental factors (eg, hygiene, asepsis) on the cases of disease that were not prevented by cefuroxime because we did not evaluate them. However, we have protocols for cleaning, disinfecting, and sterilizing the operating room, environment, and the surgical material used to minimize this effect. The surgical technique and the technical conditions in the operating rooms did not change substantially during the study, and selection bias was controlled for by including all cataract interventions in the study. In addition, the quasiexperimental design with before and after analysis provided a high level of scientific evidence even though the patients were not randomized. This gives robustness to our work compared with many studies with a retrospective design. We conclude that intracameral administration of cefuroxime in the prevention of endophthalmitis after cataract surgery seems effective and may contribute to the reduction in the incidence of endophthalmitis and, therefore, to cost reductions by preventing cases of endophthalmitis. This is 1 more prophylaxis alternative, and its impact, antibiotic spectrum, and cost effectiveness should be taken into account. WHAT WAS KNOWN Endophthalmitis is a severe complication of cataract surgery, and its incidence has been decreasing for the past decade. Studies of the incidence of endophthalmitis are common; however, most are retrospective. Intracameral cefuroxime has been shown to be effective in preventing ocular infection after cataract surgery and to be cost effective. WHAT THIS PAPER ADDS Intracameral cefuroxime reduced the incidence of endophthalmitis significantly since its introduction. It had a high clinical and economical impact; it prevented a case of endophthalmitis for every 182 patients who were administered prophylaxis.
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First author: Gil Rodríguez-Caravaca, MD, PhD, MPH Preventive Medicine Unit, Hospital Universitario Fundacion Alcorcon, Madrid, Spain