Cataract surgery is the most commonly performed surgical procedure in many developed countries,1–3 and the frequency continues to increase, probably because of changes in population structure,4 technical advances with better outcomes, and an increasing proportion of outpatient and second-eye procedures.5
Infectious postoperative endophthalmitis (IPOE) is the most dreaded complication of cataract surgery. Infectious postoperative endophthalmitis has a devastating prognosis, with a visual outcome of 20/200 or worse in 15% to 30% of cases.6–8 The severity and clinical course of IPOE depend on the virulence and the number of inoculated pathogens, as well as the patient’s immune state and the time of diagnosis and treatment.9,10 The most common pathogens remain gram-positive Staphylococcus epidermidis (or coagulase-negative staphylococci [CNS]) and S aureus (Table 1).6,10–16
Increasing resistance of Staphylococcus sp to a broad spectrum of antibiotics, including the latest fourth-generation fluoroquinolones, eg, methicillin-resistant S aureus (MRSA) and methicillin-resistant S epidermidis (MRSE), is currently a major concern.17,18 Fortunately, IPOE is a rare complication. Reported IPOE frequency varies widely, but a systematic review has shown an overall estimate of 0.128% between 1963 and 2003.2 Despite the low incidence rate, IPOE generates a substantial healthcare burden because of the high number of procedures performed and the severe consequences of overt infections.
Various operative and nonoperative measures have been advocated to prevent this serious complication.19,20 Preoperative antisepsis of the periocular area with topical povidone–iodine is widely adopted and is considered the basic standard of IPOE prevention,21 although chlorhexidine is preferred in some countries. Antibiotic prophylaxis is another commonly used preventive measure. However, proposed antibiotic prophylaxis protocols are very diverse in agents used (eg, aminoglycosides, cephalosporins, fluoroquinolones, chloramphenicol), administration routes (topical, intraocular, subconjunctival, oral, intravenous), and timing (preoperative, intraoperative, perioperative, postoperative).22–25
The European Society of Cataract & Refractive Surgeons (ESCRS) prospective randomized controlled trial of IPOE prophylaxis26 served as the basis for the 2007 ESCRS practice guidelines, which recommended systematic use of intracameral cefuroxime.10 The results were coherent, with data from over 400 000 patients in the Swedish National Cataract Registry27,28 showing an IPOE rate of 0.048%.29,30 In the Swedish National Cataract Registry, the 1.0% of cataract surgeries that did not receive intracameral cefuroxime had a significantly higher risk for IPOE (odds ratio [OR], 7.24; 95% confidence interval [CI], 3.71-14.11).29 In addition, a series of retrospective studies from France, Spain, and the United Kingdom consistently confirmed a significant decrease in IPOE rates with systematic intracameral cefuroxime injections.15,20,24,31,32
Given these data, we decided to assess the IPOE prophylaxis practice patterns and intracameral cefuroxime use in Europe in 2012, ie, 5 years after publication of the ESCRS study and guidelines.
Materials and methods
This overview was based on a comprehensive review of available literature completed by summary reports by the authors, who represented 9 European countries: Belgium, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, and United Kingdom. Identification of relevant sources and findings were discussed during meetings of the authors. Questions of interest were pooled within 5 domains: (1) Current cataract surgery procedures and known IPOE incidence rates from a National Registry or other sources; (2) nonantibiotic prophylactic measures used: hygiene rules, patient selection, antisepsis; (3) topical antibiotic use: type(s) and rationale, dose regimens; (4) intracameral antibiotic use: frequency of use, preferred type, legal incentives, or barriers; (5) guidelines: existence or absence of national practice guidelines for IPOE prevention, guideline source (health authorities, learned societies), coherence to the ESCRS 2007 guidelines. A summary of the findings in these countries is presented in Table 2.
Sweden has a long experience with intracameral cefuroxime-based antibiotic prophylaxis, which has already been highlighted. The National Cataract Register was implemented in 1992 and now covers 100% of clinics and 98.5% of procedures. Updated data covering more than 1 000 000 cataract surgeries were recently published.33 In 2010, 91 421 cataract surgery procedures were performed by 60 cataract centers (43 public, 17 private). The IPOE rate is currently less than 0.02,A whereas it was 0.1% in 1998 and 0.0595% during the 1999 to 2001 period.
Ordinary routines are followed in patient selection, hygiene rules in the operating room, and eyedrop instillation. Antiseptic showers before surgery are not used. Ocular antisepsis is based on chlorhexidine. Use of intracameral cefuroxime (1.0 mg/0.1 mL at the end of the procedure) started in 1999 and currently applies to about 90% of cataract surgery procedures, but intracameral antibiotics are used almost unanimously, with moxifloxacin as the preferred option in a few centers. Cefuroxime is prepared in various settings (local pharmacy, national pharmacy, or operating room). A combined antibiotic prophylaxis with cefuroxime and ampicillin is sometimes used in bilateral surgery or in patients with risk factors. Likewise, routine use of topical antibiotics is uncommon, but fluoroquinolones may be used in refractive lens exchange and in high-risk patients. The rate of IPOE was lower from 1999 to 2009 than in 1998, and analyses clearly showed that this was attributable to generalized intracameral cefuroxime use.
There are no formal national guidelines, but there are informal recommendations from the National Cataract Registry and the Swedish Ophthalmological Society.
In France, national guidelines on intracameral cefuroxime were recently released by the Health Ministry-governed regulatory Agence Française de Sécurité Sanitaire des Produits de Santé,18 a unique feature among the 9 reviewed countries. About 630 000 cataract procedures are performed each year by 706 cataract centers (237 public hospitals, 469 private clinics).B Endophthalmitis reporting to the national register (Observatoire National Des Endophtalmies)14 is not mandatory. Historical epidemiological studies have reported various incidence rates over time—0.32% in 1992,12 0.21% during the 2000 to 2002 period34— but the true current rate is not known.
Patients’ infection risk assessments and antiseptic showers and shampoos (povidone–iodine the day before and the morning before surgery) are routinely performed. Recommended antiseptic preparation of the operative site is based on povidone–iodine applied 3 times (10% on skin during dilation, 5% on skin and eye in the anesthesia room, 5% into conjunctival sac on the operating table). Moreover, antisepsis duration should be timed with a stopwatch (2 minutes at each step). These measures must be associated with a patient-selection process to identify infected and high-risk patients, as well as hygiene measures in the operating room applicable to staff, equipment, and the environment.18
Topical antibiotics are not recommended before cataract surgery. The national guidelines emphasize that because of their high selective power, topical fluoroquinolones should be reserved for curative treatment of severe eye infection.18 However, postoperative topical antibiotic prophylaxis is recommended during 1 week and should target common IPOE-causative bacteria, ie, gram-positive cocci.18,35 Cefuroxime (1.0 mg/0.1 mL) intracameral injection at the end of the procedure is a strongly recommended antibiotic prophylaxis in the absence of any contraindication to cephalosporins.18 The drug is usually prepared by the center’s local pharmacy. Subconjunctival injections and antibiotic prophylaxis added to the irrigation fluid are not recommended. When cephalosporin administration is contraindicated or in patients at risk, the national guidelines recommend oral levofloxacin (500 mg the day before and 500 mg on the day of surgery). In general, at-risk patients are those with diabetes mellitus, previous implantation of an intraocular device other than for cataract surgery, and previous postoperative endophthalmitis in the fellow eye; for cataract surgery only, cited risk factors are intracapsular extraction and secondary implantation. In cases of capsule rupture in patients who did not receive a preoperative systemic antibiotic, perioperative intravenous levofloxacin is recommended.18
According to a prospective longitudinal multicenter observational study that enrolled 781 patients from September 2007 to February 2008 before the ESCRS study, 28.5% of patients received preoperative topical antibiotic prophylaxis and 94.7% received postoperative topical combined antibiotic plus steroid drops.36 A recent report from 2 large centers covering 3316 patients during a 2-year period (January 2007 to December 2008) showed a 0.06% IPOE rate after the implementation of systematic intracameral cefuroxime injections.32 A recent survey showed that the use of intracameral antibiotics (cefuroxime in 60% to 73% of cases) dramatically increased from 2006 to 2011 (from 7% to 61%, respectively).C This trend is expected to increase in future years because of the publication of the national guidelines in 2011.
Data on IPOE epidemiology and practice patterns in the U.K. are fairly well known from the large series of reports published over the past decade.7,13,19,20,23,37–44 According to a recent survey by the Royal National Institute of Blind People, the number of cataract operations reached 350 602 in 2010 but fell to 338 565 in 2011 because of cost-cutting measures.D The baseline IPOE rate reported in the British Ophthalmological Surveillance Unit study was 1/700 cataract surgeries (0.14%); it was also estimated that only 62% of IPOE cases were reported.7 A 2009 review by Carrim et al.13 found that published IPOE rates during the 1997 to 2006 period (observed at single-unit, regional, or national level) varied from 0.03% to 0.2%.7,13,37–40
According to 4 surveys of ophthalmologists’ practices, subconjunctival antibiotics, predominantly cefuroxime, were administered at the end of surgery in 68% to 82% of cases compared with intracameral antibiotics in only 10% to 16% of cases.7,23,42,43 Some clinicians have argued that there is no evidence that a change from subconjunctival to intracameral cefuroxime would be more effective.45,46 Later surveys have shown a strong shift toward the use of intracameral cefuroxime, with 44.7% to 61.0% of surgeons preferring the intracameral administration route.19,44,47 A single-center retrospective analysis of 36 743 phacoemulsification procedures reported that intracameral cefuroxime was a safe alternative to subconjunctival cefuroxime with a significantly lower rate of IPOE (subconjunctival versus intracameral route: OR, 3.01; 95% CI, 1.37-6.63).20
Regarding practice guidelines, intracameral antibiotic prophylaxis is recommended for cataract surgery by the Scottish Intercollegiate Guidelines Network48 whereas the Royal College of Ophthalmologists49 leaves the details of antibiotic use to the surgeon’s discretion.
There is no national register for cataract surgery or IPOE in Spain, but some centers have developed their own local observational databases, allowing estimates of IPOE rates based on single-center samples: for instance, no cases of IPOE were observed among the 1151 cataract surgery procedures performed in 2011 at Barcelona’s Instituto de Microcirugía Ocular, with cefuroxime intracameral injections in all cases.E About 200 000 cataract procedures are performed each year.E
The following protocol, based on the ESCRS 2007 guidelines, is used very commonly in private and public Spanish institutions: preoperative prophylaxis combining lid hygiene (scrubs with baby shampoo), topical antibiotics, and povidone–iodine 10% solution applied on the skin before the patient enters the operating room, then again before starting surgery (5-minute wait), combined with a povidone–iodine 5% solution into the conjunctival sac. In case of allergy, povidone–iodine is replaced by a chlorhexidine 0.05% solution. Topical antibiotics (ofloxacin 0.3%) are used both before surgery (1 drop 3 times a day for 3 days) and after surgery (1 drop 4 times a day for 1 week).E
A retrospective survey from the University Hospital Fundación Alcorcón (Madrid) covering a 10-year period (1999 to 2008) showed a mean IPOE rate of 0.30% (95% CI, 0.26%-0.35%),24 with a significant difference in mean rates before and after the implementation of cefuroxime (1999 to 2005: 8099 patients, 0.48% IPOE rate; 2005 to 2008: 7074 patients, 0.056% rate; relative risk 0.12 [0.04-0.33], ie, a nearly 9-fold risk reduction).15 In case of a beta-lactam antibiotic allergy, intracameral vancomycin (0.1 mg/0.1 mL) was used. In another retrospective study covering 4281 cataract surgeries,31 the IPOE rate dropped from 0.5% to 0.11% after the implementation of cefuroxime.
According to the results of an annual survey by the Deutschsprachige Gesellschaft für Intraokularlinsen-Implantation, Interventionelle und Refraktive Chirurgie and Deutsche Ophthalmologische Gesellschaft (DGII/DOG) involving all major centers and encompassing half of all cataract surgery procedures, about 700 000 cataract surgeries are performed each year in Germany, 75% of which are done in private office settings.F There is no national register, but data are available from the DGII/DOG joint committee questionnaire.
Much about German practices was learned from the results of a cross-sectional anonymous survey published in 1999 by Schmitz et al.25 that analyzed 311 surgical centers (67% answer rate) and reported data on 340 633 cataract surgeries performed in 1996. The survey found a mean IPOE rate of 0.148% and provided a comprehensive picture of prophylactic treatments used at that time. The use of intraocular antibiotics (60% of the respondents) was associated with a significantly lower incidence of IPOE in both univariate and multivariate analyses (OR, 0.65; 95% CI, 0.43-0.98). However, in more than 90% of cases, the intraocular antibiotics were added to the irrigating solution; intracameral injection was used in only 5% of cases. Aminoglycoside antibiotics were used in 85% of cases, vancomycin in 7%, and a combination of vancomycin and aminoglycoside in 5%. The application of povidone–iodine (68% of respondents) to the conjunctiva was also associated with a significantly decreased risk for IPOE (OR, 0.59; 95% CI, 0.36-0.99). However, the use of preoperative topical antibiotics was associated with a significantly increased risk (OR, 2.38; 95% CI, 1.21-4.68), and a comparable trend was found with topical antibiotic use after surgery (OR, 1.3; 95% CI, 0.87-1.92).25 A later and comparable survey involving 538 centers and more than 400 000 cataract procedures found a 0.072% IPOE overall rate.50
Currently, povidone–iodine 5% is usually applied on the ocular surface during 5 + 5 minutes. Various topical antibiotics (quinolones, aminoglycosides) are applied before, during, and after the procedure for 1 to 4 weeks.F A recently published single-center retrospective survey including more than 26 500 procedures found a 0.06% IPOE rate when prophylaxis was based on topical povidone–iodine and gentamicin-containing irrigation fluid administered preoperatively.51
Use of intracameral cefuroxime commenced after the publication of the ESCRS 2007 guidelines. Intracameral cefuroxime is currently used in an unknown proportion of procedures, probably fewer than 20%, because specific legal issues oppose this practice. There are no national IPOE prevention guidelines, but German ophthalmologists tend to follow the ESCRS 2007 recommendations.
The estimated annual number of cataract surgery procedures is 120 000.G The number of active centers is unknown. Belgium does not have a mandatory registry of postoperative complications after cataract surgery, thus current figures are not known. However, IPOE incidence at the Antwerp University Hospital is 0.0% since the voluntary registry of the cataract surgeries performed at this center in the European Registry for Quality Outcomes of Cataract and Refractive SurgeryG (partner countries: Austria, Belgium, Denmark, Finland, Greece, Germany, Hungary, Ireland, Italy, the Netherlands, Norway, Slovakia, Spain, Sweden, Turkey, and U.K.).5
Only limited information about current national practice trends is available, but implementation of the ESCRS endophthalmitis guidelines started in 2009. No endophthalmitis occurred during the past 2 years at the Antwerp University Hospital where this protocol is routinely used.G Regarding other routine prophylactic measures, patients are checked before surgery for infection and povidone–iodine (5% on ocular surface, 10% on skin over 3 minutes) is used as an antiseptic without prior shower and no preoperative topical antibiotics. Hygiene rules at the operation are focused on a standardized protocol for sterile draping. Topical antibiotics, mainly quinolones, are used during and after surgery, according to licensed doses. Cefuroxime (1.0 mg/0.1 mL intracameral route or during incision hydration) is used in 100% of cataract surgery procedures, according to the ESCRS 2007 guidelines.
A large but unknown number of Italian cataract centers perform an estimated 300 000 to 400 000 cataract surgery procedures per year.H Although there is no national register, the incidence of IPOE has been estimated to be 0.05% to 0.35%, ie, similar to other European figures.4
Prophylactic measures usually start with the screening of high-risk patients for local risks (blepharitis, dacryocystitis, severe dry eye), systemic comorbidities (diabetes mellitus, immunosuppression, pulmonary infections, sustained antibiotic/steroid therapy), and very high age (>85 years old). The reported data are the result of a survey conducted in 2010 by the Italian Association of Cataract and Refractive Surgeons. An eyelid cleaning is advised during the week before surgery. Antiseptics are used in 100% of the procedures, mainly povidone–iodine (10% on periocular skin, 5% on ocular surface [conjunctival fornix] applied for at least 3 minutes) or chlorhexidine 0.05% in case of povidone–iodine allergy. Routine hygiene and draping rules and single-dose eyedrops are used. A wide-spectrum topical antibiotic (aminoglycosides, fluoroquinolones) is used during the preoperative phase in 76% of cases,52 during the procedure in 41%, and postoperatively in all patients.
Intracameral antibiotics have been used since 2008, following the ESCRS 2007 guidelines and legal aspects. Currently, either cefuroxime (1.0 mg/0.1 mL; 52%) or vancomycin (48%) is used in 41% of procedures.52 Syringes are prepared by local pharmacies. Since there are no specific national guidelines, Italian surgeons tend to follow the ESCRS 2007 recommendations, but the reference source is mainly surgeon-dependent.
In the Netherlands, 140 000 cataract surgery procedures are performed each year, 80% in general hospitals, 12% in academic hospitals, and 8% within an increasing number of ambulatory surgery centers with multiple facilities.I Outcome registration is mandatory for all surgeons, as requested by the Dutch Ophthalmological Society and the Netherlands IntraOcular Implant Club. According to these databases, the IPOE rate is 0.03%.J
Povidone–iodine eyedrops in a concentration varying from 0.3% to 5.0% are instilled preoperatively (0.3% is available as a commercial preparation for topical use), and then povidone–iodine 5% to 10% is applied on the skin and diluted solution (dilution according to surgeon’s preference) on the ocular surface for 0.5 to 3.0 min. Class 1 hygiene rules are applied to the operating room.53 Topical antibiotics are often used before, during, and after the procedure; administrations and dosages vary. Use of intracameral antibiotics started in 2007 after the publication of the ESCRS 2007 guidelines and was used in approximately 27% of procedures in 2010.J Syringes are prepared at the hospital’s pharmacy.
In the absence of specific guidelines from national health authorities and on the basis of the low endophthalmitis rate of 0.03% in the Netherlands, the Dutch Ophthalmological Society recommends cefuroxime in high-risk cases only (capsule breaks, clear cornea incisions). Systematic use is considered debatable.
A retrospective review of all consecutive patients treated for acute IPOE after cataract surgery (N = 250) in a single center from 1996 to 2006 was recently published.16 Bacterial cultures (250 cases) showed bacterial growth in 66.4% of cases. Of these, 53.6% revealed gram-positive CNS, 38.0% other gram-positive bacteria, 6.0% gram-negative pathogens, and 2.4% polymicrobial cultures.
According to the national health insurance refunding system, 152 000 cataract surgery procedures were performed in Poland in 2011. About 15 000 to 20 000 additional cataract surgeries are performed in private practices, although their exact number is not known.K No reliable data on current IPOE incidence rates are available. A survey published in 2004 assessed data from 53 ophthalmology centers in Poland, involving 28 674 cases of routine cataract surgery, 6518 cases of complicated cataract surgery, 1387 cases of combined cataract and glaucoma surgery, and 2978 cases of glaucoma surgery. The prevalence of IPOE in this group of patients ranged from 0.29% after cataract surgery to 0.93% after complex surgery (cataract and glaucoma).54 These high incidence rates were interpreted as possible selection bias due to the small size of the study sample. In addition, IPOE was not proven by culture or polymerase chain reaction so some cases of toxic anterior segment syndrome might have been included.
In the absence of an accurate national observational database, the following information applies to the protocol used in a single center in Warsaw onlyK: Prophylactic measures include patient selection, antiseptic showers before surgery, and systematic povidone–iodine 5% antisepsis on the ocular surface for 1 to 3 min. Routine sterile environment is respected in the operating room. Topical antibiotics are applied before, during, and after surgery. The drug of choice is levofloxacin, and the administration schedule is 1 drop twice daily the day before surgery, 1 drop before surgery, 1 drop during and the night after surgery, 1 drop 4 times a day for 2 weeks after surgery. In high-risk patients (blepharitis, complicated cases), the postoperative dosage is increased to 1 drop every 2 hours on the day of surgery.
Although no hard data are available, intracameral antibiotics are probably not injected in most procedures because of off-label use and complex preparation.K However, cefuroxime (1.0 mg/0.1 mL) has been used in 100% of the procedures in the Warsaw center since 2005; until 2012, the preparation was outsourced to a commercial pharmacy, but currently syringes are prepared in the operating room.
Specific national guidelines have been prepared and are now in the process of being approved. The Polish Society of Ophthalmologists’ recommendations are similar to the ESCRS 2007 guidelines.
We found that the current practice patterns for IPOE prophylaxis between European countries differ significantly and often diverge from the antibiotic prophylaxis practices recommended by the ESCRS guidelines. The data reported in the present overview come from heterogeneous sources: Swedish data are based on a national register with a high coverage; Dutch IPOE rates are based on a mandatory outcome reporting and practice trends; IPOE rates in the U.K. were described by a series of dedicated surveys; in some other countries, data about the volume of cataract surgeries, IPOE prophylaxis practice patterns, and IPOE incidence rates are more or less unknown because an adequate national epidemiological system does not exist. Between these extremes, a variable amount of reliable data documents exists in the remaining countries.
While acknowledging that the variability of source data limits our study’s value, we believe that this limitation is not specific to this review but rather reflects the lack of adequate epidemiologic tools and systematic reporting in most countries. In addition, this overview can by no means determine whether differences in practice patterns and hygiene routines are reflected in the varying IPOE rates. One also has to consider a possible bias since centers participating in surveys or reporting systems may be more attentive to all steps in the processes of patient preparation and surgical procedures. Thus, the present overview does not pretend to report actual practice patterns and epidemiological facts in the reviewed countries or to provide answers to why the IPOE rates differ, but it probably offers a fair picture of the current status in this field. It also helps to explain why the ESCRS guidelines are not yet consistently adopted in these countries.
Practice patterns for general hygiene rules in the operating room and systematic preoperative antisepsis with povidone–iodine or chlorhexidine tend to converge. The use of preoperative antisepsis with povidone–iodine (5% solution on the conjunctiva and cornea and 5% to 10% solution on the periorbital area for ≥3 min) is based on a microbiological and clinical rationale since it has been shown to diminish the bacterial load and prevent IPOE.21,25,55–58 Its use is recommended by current guidelines.10,17,18 If povidone–iodine is contraindicated, chlorhexidine 0.05% is an alternative.10,18,59 The use of chlorhexidine as a primary antisepsis agent in Sweden has proven efficient and safe over a long period.33,60
Regarding antibiotic prophylaxis regimens, data of landmark importance came out of the ESCRS randomized trial, which comprised 16 603 patients and compared (1) intracameral cefuroxime (1.0 mg/0.1 mL) bolus injections at the end of cataract surgery with no intracameral cefuroxime and (2) topical perioperative levofloxacin 0.5% eyedrops with no perioperative topical levofloxacin. Topical levofloxacin was given in all groups postoperatively. The results showed a nearly 5-fold decrease in the risk for presumed and proven IPOE when intracameral cefuroxime was included.4 The effect of topical perioperative levofloxacin was not significant. The incidence rates were 0.345% for total IPOE and 0.247% for proven IPOE in the group with placebo drops and no intracameral cefuroxime, which may be regarded as the true current background rates of IPOE after phacoemulsification in Europe in the absence of antibiotic prophylaxis.4
Our overview shows that postoperative topical antibiotic prophylaxis is also commonly used in all countries (except Sweden), particularly in clear corneal incision surgery, for up to 2 weeks.10,18 Its efficacy, however, is not proven or only weakly proven by retrospective studies.61,62 In the ESCRS study, levofloxacin was administered to all groups postoperatively. According to the authors, the relatively high incidence rates of IPOE in subgroups without intracameral cefuroxime suggested that postoperative levofloxacin alone conferred little benefit. An alternative explanation is that had this type of antibiotic prophylaxis not been used, the rates across all groups would have been higher.4
Much wider variation in preoperative and perioperative topical antibiotic prophylaxis regimens, as well as intracameral cefuroxime, is observed in this overview. The ESCRS study has not assessed the role of preoperative topical antibiotic prophylaxis. A previous systematic review concluded that its efficacy was not yet scientifically proven.21 Thus, the ESCRS 2007 guidelines cite preoperative topical antibiotic prophylaxis as an option to consider,10 while the French 2011 guidelines do not recommend it.18 Subconjunctival antibiotic prophylaxis has also been used over the past 30 years, particularly in the U.K. However, on the basis of available data, the ESCRS guidelines stated that it probably has little prophylactic effect on the prevention of IPOE9,10,21 and the French 2011 guidelines do not recommend its use.18
Intracameral cefuroxime is recommended by ESCRS and French guidelines,11,13 by the Scottish Intercollegiate Guidelines Network,48 and by Canadian guidelines,63 while details of antibiotic use are left to the individual surgeon’s discretion by the Royal College of Ophthalmologists49 and the American Academy of Ophthalmology.17
Ophthalmologists tend to follow the ESCRS recommendations for intracameral cefuroxime in many European countries lacking national guidelines, but legal barriers may oppose its use. Controversy about the scientific rationale for systematic intracameral cefuroxime persists in the U.K., where the subconjunctival route has been historically dominant and in the Netherlands where its use is limited to high-risk patients. Generally, persisting controversies about the scientific rationale for systematic use, legal barriers, and the lack of a commercially available preparation appear to have conferred major practical barriers to intracameral cefuroxime’s widespread use,18,44,64 although a commercially available product is currently being introduced.
Cefuroxime is a second-generation cephalosporin that is effective against most bacteria that cause IPOE,26 in particular staphylococci and streptococci (except MRSA, MRSE, and Enterococcus faecalis). It is also effective against gram-negative bacteria (except Pseudomonas aeruginosa) and P acnes. Bactericidal cefuroxime concentrations of 2742 mg/L are achieved within 30 seconds of intracameral injection and drops to 756 mg/L 1 hour later.27 This was the rationale for establishing the administration regimen still in use (1.0 mg/0.1 mL at the end of phacoemulsification cataract surgery before the wound is closed), which started in Sweden 13 years ago.27–30,33 The regimen has been further supported by the ESCRS randomized trial results4 and additional retrospective studies in France, Spain, and the U.K.20,24,31,32 Intracameral cefuroxime has been shown to have a good safety profile, with no evidence of increased endothelial cell loss or any proof of increased blood–aqueous barrier disturbance.28 The main disadvantage with cefuroxime may instead be the gaps in its antimicrobial spectrum. Notably, there is a striking convergence between the very low IPOE rate in Sweden (<0.040%; 1992–2009),33 where intracameral cefuroxime is used in 90% of cases, mostly without topical antibiotic prophylaxis, and the equally low rate reported in the Netherlands (0.03%),J where topical antibiotics are the basis of IPOE prophylaxis while intracameral cefuroxime is used in only 27% of cases.
Considering the significant differences in IPOE rates seen in scientific reports (including the ESCRS randomized trial), it may appear a bit surprising that intracameral cefuroxime is still far from being consistently adopted by European ophthalmologists either systematically or in targeted cases (ie, high-risk patients). However, it should be noticed that the comparative evidence base is incomplete; for instance, the ESCRS trial did not answer many relevant questions such as the relative efficacy of intracameral cefuroxime compared with a full course of preoperative, perioperative, and postoperative topical antibiotics; subconjunctival injections; or antibiotics in irrigation fluid. Although a systematic comparison of all possible options in large randomized trials is not feasible, it may explain why these ophthalmologists remain unconvinced that they should have changed their practices.
It has been suggested that topical fourth-generation fluoroquinolones such as moxifloxacin and gatifloxacin would be preferable to intracameral cefuroxime, among other things because of their broader spectrum of activity.61,65–67 Fourth-generation fluoroquinolones were the most frequent topical antibiotic prophylaxis used by the American Society of Cataract and Refractive Surgery survey respondents in 2007,64 and their efficacy and safety are further supported by a retrospective study involving 29 276 cataract surgeries.68 Other studies have also reported that intracameral moxifloxacin is safe for IPOE prophylaxis.69,70 The ESCRS guidelines, on the other hand, state that the use of topical fourth-generation fluoroquinolones, similar to that of intracameral vancomycin, raises ethical questions about the use of reserve antibiotics for prophylaxis, as opposed to treatment of established IPOE,10 and the French guidelines state that “topical fluoroquinolones are reserved for curative treatment of severe eye infections.”18
Managing patients with contraindications for cefuroxime is a rare issue. Anaphylactic hypersensitivity reactions, occurring a few minutes after intracameral cefuroxime injection, have been reported27,71–73 but are extremely rare, the risk being estimated at 0.0001% to 0.1%.19,74,75 In patients with a known allergy to cephalosporins, cefuroxime is not recommended.10,18 Suggested alternatives are intracameral injection of vancomycin with intensive topical quinolones (eg, levofloxacin, which may be a useful adjunct for coverage of gram-negative bacteria)10 or preoperative oral levofloxacin.18
Antibiotic prophylaxis should be regarded as one component of a global effective strategy for the control of healthcare-associated infections.48 The first line of prevention must always be general hygiene and asepsis measures, which encompass patient selection, hygiene rules in the operating room, and surgical site antisepsis. As stated by the Scottish Intercollegiate Guidelines Network, antibiotics may then be used in a manner that is supported by evidence of effectiveness, minimizing the effects on the patient’s normal bacterial flora and causing minimal change to the patient’s host defenses.48 To prevent resistance development, guidelines have recommended limiting the prescription of oral fluoroquinolones to high-risk patients (eg, severe atopic dermatitis).10,76
Pathogens found in proven IPOE cases mostly originate from the eye-surrounding flora,56 and the microbial spectrum is dominated by gram-positive staphylococci and streptococci. Intraocular contamination by the facultative pathogenic surrounding flora has been shown to occur in a high proportion of the procedures.10,77–84 Still, the development of a true IPOE is rare. In the ESCRS study, 5 significant risk factors for IPOE development were identified: clear corneal incisions versus scleral tunnel, surgical complications, silicone versus acrylic intraocular lenses (IOLs), less experienced surgeon versus more experienced surgeon, and no use of intracameral cefuroxime.4 Notably, factors such as the use of an IOL injector, immunosuppression, diabetes mellitus, and the use of perioperative topical levofloxacin did not affect the IPOE rate significantly in the ESCRS study.4 It should be emphasized, however, that the literature regarding many of these IPOE risk factors is contradictory. Although some risk factors (such as capsule rupture and vitreous loss) are undisputable, the occurrence of an IPOE is very difficult to predict, which emphasizes the importance of an effective prophylactic strategy in routine practice.
In conclusion, intracameral cefuroxime reduces the risk for IPOE after cataract surgery, as shown by the ESCRS study and multiple retrospective European studies, and is recommended by the ESCRS and the national guidelines in France.
Five years have passed since the publication of the ESCRS study, but the IPOE prophylaxis routines, including the use of intracameral cefuroxime, still vary widely between European countries. There is a convergence in antisepsis routines with povidone–iodine and in the use of postoperative topical antibiotics (despite the findings of the ESCRS study), with few exceptions. On the contrary, the use of preoperative and intraoperative topical antibiotics and the use of intracameral or subconjunctival antibiotics differ significantly between, and also within, countries.
Controversies about the scientific rationale for intracameral cefuroxime use in some countries, legal barriers, and the lack of a commercially available preparation appeared to be the major obstacles to systematic application of this routine.
1. Tan CS, Wong HK, Yang FP. Epidemiology of postoperative endophthalmitis in an Asian population: 11-year incidence and effect of intracameral antibiotic agents. J Cataract Refract Surg
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