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Tutorial
Introduction
Strategy
Antibiotics
References

Slides

 Cataract and IOLs

Endophthalmitis Prophylaxis in Cataract Surgery

Robert W. Snyder, MD, PhD · James Lee, MD

Introduction

There are more than 2 million cataract surgeries performed each year in the United States. Fortunately, the incidence of postoperative endophthalmitis is relatively low, with an estimated five to 10 cases per 10,000.1,2 When endophthalmitis occurs, the outcome for the patient can be devastating. Therefore, there is much interest in minimizing the occurrence of endophthalmitis. However, because the incidence is so low, there are few well-controlled studies of the risk factors or efficacy of preventive measures. Preoperative disinfection of the surgical site and meticulous attention to sterile technique are essential. The role played by perioperative antibiotics is uncertain. There are no prospective and controlled studies that address the use of preoperative, intraoperative, or postoperative antibiotics, nor is there a choice of which classes of antibiotics are appropriate in the perioperative period.

Slide 1

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Phage typing and DNA fingerprint analysis have shown that the organisms that cause postoperative endophthalmitis, despite their low virulence in other surgical settings, are those that reside on the patient's own lid flora and adnexa.3,4 Staphylococcus epidermidis is the most common infecting bacteria, followed by Staphylococcus aureus, and rarely, gram negative rods or even Candida (Slide 1). Staphylococcal bacteria are ubiquitous and S. epidermidis is considered normal flora on the skin and lid.

In the operating room, it is imperative to have a "sterile technique," but it is not uncommon for the anterior segment to become contaminated during cataract surgery. Reports suggest that bacteria can be isolated from anterior chamber fluid up to 43% of the time following cataract surgery.5,6 Despite this, endophthalmitis is still a rare occurrence.

It appears that there may be a threshold inoculum necessary to cause endophthalmitis. In primate studies, small numbers of S. aureus did not cause infection, whereas inoculation with 104 or greater organisms were necessary to induce infection when the capsule was intact.7

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Strategy

Table. Recommendations for preventing endophthalmitis

•  Identify and treat preoperative blepharitis.

•  Reduce inoculum. Preoperative antibiotic Ocuflox four times a day start 1 day preoperatively.

•  Betadine 5% to cul-de-sac, lids, and skin 2 minutes contact as a preoperative preparation.

•  Isolate the lids.

•  Although most cases of endophthalmitis arise from the host flora, other sources are also important.

•  Avoid prolene haptics.

•  Administer postoperative topical antibiotics until the epithelium is healed.

•  Consider oral ofloxacin for special cases in which the risk is high.

Given that the majority of organisms come from the patient's own flora, the most reasonable way to decrease the potential inoculum is to decrease the number of organisms on the lid margin or in the cul-de-sac. This can be effectively done using povidone-iodine, such as Betadine (povidone-iodine 5%, Escalon Ophthalmics), or povidone-iodine plus antibiotics. Povidone-iodine has been shown to significantly decrease the incidence of endophthalmitis, and is effective in reducing the number of organisms in the cul-de-sac.8-10

Povidone-iodine releases free iodine, which kills organisms via oxidation. As an oxidizing agent, it requires time for killing; in vitro experiments suggest 1 to 2 minutes of contact time. It is advised to prep the lid margin skin and place 5% Betadine directly into the cul-de-sac so that it has at least 1 or 2 minutes of contact time with the tissue. More dilute povidone-iodine solutions have adequate amounts of free iodine and are also effective; however, the less concentrated solutions are not as stable and must be made up fresh.

Preoperative antibiotics have also been advocated in addition to using preoperative Betadine because antibiotics further decrease the number of organisms, both on the lid margins and in the cul-de-sac. 11-13 There are no controlled prospective studies that prove a decrease in the incidence of endophthalmitis with the use of preoperative antibiotics.

In a recent report by Colleaux, a retrospective evaluation of 13,886 phacoemulsification procedures revealed a benefit to the use of preoperative antibiotics in reducing the risk of endophthalmitis in clear cornea surgery.14 In a different experimental protocol, it has also been shown that the number of anterior segment taps positive for bacterial contamination is decreased to approximately 5%, with preoperative Ocuflox (ofloxacin ophthalmic solution, Allergan).15 Unfortunately, this experiment did not have a control arm of Betadine alone and the results are compared to the historical value, approximately 40%. Despite the lack of definitive evidence from prospective controlled studies, the use of preoperative antibiotics is still recommended.

Preoperative antibiotics have little intrinsic risk. The choice of antibiotic is most likely more controversial. The ideal antibiotic would have broad spectrum, would be nontoxic, and would have a fast killing time. Using these criteria, the fluoroquinolones would be the best choice.

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Antibiotics

Slide 2

SLIDE 2 View full size slide
Slide 3
 Among the fluoroquinolones, both Ciloxan (ciprofloxacin HCl, Alcon) and Ocuflox have been shown to have comparable spectrums of activity (Slide 2),16 comparable kill times (Slide 3), 17 and are both relatively safe. Because Ocuflox is more soluble (pH 7.0), it has better tissue penetration.18 Aggressive dosing of Ocuflox (1 drop every 5 minutes five times preoperatively) can yield approximately 1 µm of Ocuflox per milliliter of aqueous.19

Similar unpublished studies show results with 2 drops every 30 minutes two times. This is above the minimum inhibitory concentration (MIC) for many strains of S. epidermidis. Therefore, Ocuflox is more favorable than Ciloxan. Quixin (5% levofloxacin, Santen) is the L isomer of ofloxacin. It may have more favorable MIC levels and attain higher tissue penetration, although the safety of the formulation has not been reported with regard to epithelial wound healing.

Other surgeons recommend less expensive and older antibiotics and those may be effective, as well. There are no comparative, prospective studies to indicate whether the aminoglycosides or chloramphenicol plus Betadine are significantly less effective than the fluoroquinolones. However, these medications are not as broad in their coverage and not as effective against both gram-negative and gram-postitive organisms.

Slide 4

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There are other measures that are generally accepted and recommended to reduce the inoculum. It has been traditionally advocated and is important to identify patients with active blepharitis, treat them, and avoid intraocular surgery until their lid disease is controlled. Daily lid scrubs with an adjunctive antibiotic or antibiotic/steroid ointment to the lids at bedtime can be effective. In cases with concomitant ocular rosacea, tetracycline 250 mg four times a day for 1 month or doxycycline 100 mg/day will help control the meibomianitis. Additionally, isolation of the lids with adhesive tape or plastic tape dressing is recommended (Slide 4). This prevents meibomian secretions or debris surrounding the hair follicles from contacting the surgical site.

The use of intraoperative antibiotics remains controversial. A number of investigators have suggested that aminoglycoside and vancomycin used intracamerally, or vancomycin alone, injected in the bag can significantly reduce the risk of endophthalmitis.20-22 A survey conducted by the American Society for Cataract Slide 5

SLIDE 5 View full size slide
and Refractive Surgeons has shown that at least 35% of ophthalmic surgeons currently use intracameral antibiotics. Vancomycin was used by 80% and gentamicin by more than 40% of the surgeons surveyed.23 Although the anecdotal and retrospective analyses are appealing and show that the relative risk of endophthalmitis is reduced, there is no solid prospective evidence in the peer-reviewed literature to support this practice. Additionally, there is some potential for causing toxicity. Gentamicin has a narrow therapeutic/safety range and significant retinal toxicity can occur above 100 µm/cc, while vancomycin can cause cystoid macular edema. Ruth Axer Siegel, MD, and colleagues, showed that vancomycin increased the risk of clinically significant CME as well as CME as demonstrated by fluorescein angiography at both 1 month and 4 months after cataract surgery (Slide 5).24 This has not been the experience of Howard V. Gimbel, MD, who injects the drug directly into the bag at the conclusion of surgery.22

Intracameral antibiotics may be appropriate; however, vancomycin does not appear to be the right choice. Ferro and colleagues showed that adding vancomycin and gentamicin did not statistically reduce the number of anterior segment aspirates that were positive for bacteria following cataract surgery.25

Additionally, work by Feys and colleagues showed that vancomycin in the irrigant did not decrease the incidence of contamination of the anterior segment for cases that were cultured at the end of surgery.26 The reason for this apparent lack of efficacy is most likely related to the contact time and kill curve for the antibiotic chosen.

Slide 6

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Vancomycin injected at 20 µm/cc has been shown to have a half-life of approximately 2 hours, which is relatively short.25 This is important because vancomycin is relatively slow at killing organisms and may require 8 to 12 hours to reduce the inoculum by 3 logs for S. aureus (Slide 6).27 This is even more significant considering that a lag phase in the growth curve undoubtedly occurs when bacteria are placed into the eye and into a new growth environment.

Vancomycin requires actively growing bacteria to be effective and will not work unless the bacteria are in active phase. At the time in the growth curve when vancomycin could be effective in killing the inoculum, the concentration of vancomycin may be lower than the therapeutic range.

In lieu of vancomycin, one would more likely benefit from having an antibiotic that is fast-killing (3 logs of killing in 2 hours or less), has broad-spectrum killing of both gram-negative and gram-positive organisms, and one in which the antibiotic concentration can be augmented and maintained with supplemental topical antibiotics. In the future, perhaps a fluoroquinolone antibiotic with these preferred requirements will be found to be useful.

Postoperative subconjunctival injections of antibiotic have also been practiced for many years. The benefit could come from delivery of therapeutic levels of antibiotic to the anterior chamber, which would result in the reduction of bacteria numbers and prevent clinically significant endophthalmitis.

In prospective studies, Christy was not able to show a benefit from subconjunctival antibiotic alone, but did have a benefit from subconjunctival plus preoperative topical antibiotic.28,29

More recent retrospective analysis by Drs. Colleaux and Hamilton revealed a statistically significant reduction in the incidence of endophthalmitis when subconjunctival antibiotics were used.14 Unfortunately, the researchers did not distinguish between subconjunctival gentamicin versus a combination of gentamicin and cefazolin.

Gentamicin is toxic to the retina and there is significant concern among retina surgeons as to the safety of routine postoperative injections of gentamicin.30,31 Cefazolin alone has not been established as effective in scientific studies. However, subconjunctival injection of cefazolin is probably much safer and deserves further evaluation. With the trend toward clear cornea and topical or intracameral anesthetic, the use of subconjunctival injections is less practical.

Postoperatively, endophthalmitis can still occur via contamination of the anterior segment while the wound is still open. This may be a problem with clear cornea and topical anesthesia, or even scleral wound incisions that may gape and take contaminated fluid back into the eye. Because of this, continued antibiotic therapy is advised until the epithelial barrier has been reestablished.

The ideal choice of antibiotic would again be one with broad-spectrum, fast-acting, relatively high solubility, and relatively sustained tear film levels with low toxicity. Again, the fluoroquinolones are the best choice. Ofloxacin is the most favorable choice because it has the best solubility at pH 7, relatively good penetration, and persists in the tear film for relatively long periods of time.18,32 Levofloxacin may prove to be superior; however, toxicity studies remain to be completed.

Attention to adequate wound closure is also important. It is recommended to check the wound with fluorescein when the case is over, injecting balanced salt solution into the stroma to enhance the seal if necessary or placing a suture if there is persistent leakage or if the patient is expected to have compromised wound healing.

Prolene haptics can increase the risk of endophthalmitis by approximately 4.5 times.33 This is due to the ability of Staphylococcus to directly bind to prolene. The elimination of prolene haptics may be necessary to maximally reduce the risk of endophthalmitis. Additionally, a surgeon should avoid directly contaminating the IOL by not placing it on the eye or touching it to the lid margins.

Sterile technique is an important prevention method. This includes following manufacturer's recommendation regarding sterilization and use of disposables. Excessive talking and coughing have been implicated as not being sterile in repeated cases and should be kept to a minimum.

In the report of Menikoff and colleagues, the highest risk for endophthalmitis (14 times) occurred with capsule rupture.33 In such high-risk cases, the addition of antibiotics that reach therapeutic levels in the vitreous may be appropriate. Subconjunctival antibiotics are generally not believed to reach high enough vitreous levels.34,35,36 Systemic antibiotics have not been traditionally found to effectively cross the blood-brain barrier.

More recently, the fluoroquinolones have been found to penetrate the eye well because of their increased lipid solubility. Ofloxacin seems to be approximately two times better than ciprofloxacin.37 Oral ofloxacin 400 mg twice a day in conjunction with topical Ocuflox has been shown to reach a concentration of approximately 2.7 µm/cc in the aqueous and vitreous.38 This is therapeutic for most organisms.

In the higher risk cases, the addition of systemic ofloxacin 400 mg twice daily for 3 days, with 2 days of Ocuflox 0.3% every 2 hours is recommended. This regimen should not be adapted to all cases because of the risk of increased resistance to fluoroquinolones and the increased medical costs.

Posted October 2001

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References

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  2. Kattan HM, Flynn HW Jr, Pflugfelder SC, Robertson C, Forster RK. Nosocomial endophthalmitis survey: Current incidence of infection after intraocular surgery. Ophthalmology. 1991;98:227-238.
  3. Speaker MG, Milch FA, Shah MK, Eisner W, Kreiswirth BN. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology. 1991;98:639-650.
  4. Locatcher-Khorazo D, Gutierrez E. Bacteriophage typing of Staphylococcus aureus. Arch Ophthalmol. 1960;63:774-787.
  5. Dickey JB, Thompson KD, Jay WM. Anterior chamber aspirate cultures after uncomplicated cataract surgery. Am J Ophthalmol. 1991;112:278-282.
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  14. Colleaux K, Hamilton WK. Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. Can J Ophthalmol. 2000;35:373-378.
  15. King KM, Thompson KD, Bouchard CS. Anterior chamber aspirate culture following uncomplicated cataract surgery in patients pretreated with topical ofloxacin. Invest Ophthalmol Vis Sci. 1993;34(4):884. Abstract 913.
  16. Jensen HG, Felix C and the In Vitro Antibiotic Testing Group. In vitro antibiotic susceptibilities of ocular isolates in North and South America. Cornea. 1998;17(1):79-87.
  17. Callegan MC, Booth MC, Gilmore MS. In vitro pharmacodynamics of ofloxacin and ciprofloxacin against common ocular pathogens. Cornea. 2000;19(4):539-545.
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  19. Bouchard CS, King KK, Holmes JM. The kinetics of anterior chamber ofloxacin penetration. Cornea. 1996;15(1):72-75.
  20. Gills JP. Filters and antibiotics in irrigating solution for cataract surgery [letter]. J Cataract Refract Surg. 1991;17(3):385.
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  22. Gimbel HV. Letter. Ophthalmology. 2000;107(9):1614-1615.
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  25. Ferro JF, de-Pablos M, et al. Postoperative contamination after using vancomycin and gentamicin during phacoemulsification. Arch Ophthalmol. 1997;115:165-170.
  26. Feys J, Salvanet-Bouccara, Edmond J, Dublanchet A. Vancomycin prophylaxis and intraocular contamination during cataract surgery. J Cataract Refract Surg. 1997;23:894-897.
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  31. McMillan JJ, Mead MD. Prophylactic subconjunctival antibiotics after cataract extraction - evaluation of their desirability and efficacy. Int Ophthalmol Clin. 1994;34:43-49.
  32. Donnenfeld E, Malka N, Perry H, Wenger L, Sforza PD, Kornstein H. Antibiotic stability in the tear film following topical application. Invest Ophthalmol Vis Sci. 1999;40(4):S548. Abstract nr 2896.
  33. Menikoff JA, Speaker MG, Marmor M, Raskin EM. A case-control study of risk factors for postoperative endophthalmitis. Ophthalmology. 1991;98(12):1761-1768.
  34. Barza M, Lynch E, Baum JL. Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits. Arch Ophthalmol. 1993;111:121-125.
  35. Barza M, Doft B, Lynch E. Ocular penetration of ceftriaxone, ceftazidime and vancomycin after subconjunctival injection in humans. Arch Ophthalmol. 1993;111:492-494.
  36. Rubinstein E, Triester G, Avni I, Schwartzkopf R. The intravitreal penetration of cefotaxime in man following systemic and subconjunctival administrations. Ophthalmology. 1987;94:30-34.
  37. Grayson G, Flowers C, Nassaralla B, Dewan N, Esrail R, McDonnell PJ. Aqueous penetration of 0.3% ciprofloxacin and 0.3% ofloxacin after topical application and a microbial analysis of pretreatment conjunctiva and post-treatment aqueous humor. Invest Ophthalmol Vis Sci. 1995;40(4):S160. Abstract nr 783.
  38. Donnenfeld E, Perry H, Snyder R, Moadel K, Elsky M, Jones H. Intracorneal, aqueous humor, and vitreous humor penetration of topical and oral ofloxacin. Arch Ophthalmol. 1997;115(2):173-176.
Callegan MC. Data graph received from personal communication.

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