After a flawless phacoemulsification, the return of the patient a few days later with decreased vision, a hypopyon, and endophthalmitis is devastating. Surgeons employ various means to decrease the incidence of postsurgical infection. Some of these strategies have proven scientific merit, whereas others have “softer” indications. Proponents of using intracameral antibiotics during cataract surgery assert that the practice decreases the rate of endophthalmitis because it is better able, compared with not using an intracameral antibiotic, to eradicate organisms that enter the eye during or immediately after cataract extraction.
For an antibiotic to work effectively, however, it must have adequate contact time and concentration. The most popular intracameral agent is vancomycin. This glycopeptide works by inhibiting cell-wall synthesis and is therefore a time-dependent killer. The antibiotic is highly active against gram-positive cocci, which account for the great majority of endophthalmitis cases. Its antibacterial activity, however, is slow and time-dependent. In other words, vancomycin must have prolonged contact with susceptible bacteria in order to kill them.
Interestingly, a suspension of Staphylococcus aureus or Staphylococcus epidermidis incubated in BSS containing a standard concentration of vancomycin (20µg/mL) showed no decrease in the number of viable organisms for up to 120 minutes.1 Due to the constant turnover of aqueous, the concentration of a drug in the anterior chamber would decrease by one-half in 70 minutes, although it may decrease even more rapidly due to quicker aqueous dynamics in the postoperative, inflamed eye.1 This in vitro model therefore does not support the assertion that antibiotics in the irrigating solution lower the rate of endophthalmitis. I would argue that the safety and efficacy of this prophylactic method are unsupported.HOW DID THIS PRACTICE START?
James Gills, MD, of Tarpon Springs, Florida, wrote a letter to the Journal of Cataract and Refractive Surgery in 1991 that described his experience with intracameral antibiotics.2 In it, he stated that he had had one case of endophthalmitis in 20,000 cataract surgeries for which he had added gentamicin to the infusion fluid (a final concentration of 8µg/mL). With the addition of vancomycin to the infusate (a final concentration of 20µg/mL), he had a single incident of endophthalmitis in 9,928 cases. Interestingly, when both gentamicin and vancomycin were added to the bottle, no cases of endophthalmitis occurred in 25,000 cases.
Dr. Gills' letter prompted many surgeons to begin adding antibiotics to the irrigating solution. A careful statistical analysis of this case series, however, revealed no statistically significant difference among the gentamicin, the vancomycin, and the combined gentamicin/
vancomycin groups.3 Additionally, it is important to note that the series did not include a control group (eg, eyes in which cataract surgery was performed without the addition of antibiotics in the irrigating fluid) for comparison. Dr. Gills' results do not support his conclusion that antibiotics in the irrigating fluid prevent endophthalmitis.
More recently, Dr. Gills reported using intracameral vancomycin and ceftazidime at the end of each phacoemulsification and cited an endophthalmitis rate of 1:20,000 cases.4 In addition to intracameral antibiotics, he checked patients' IOP 20 to 30 minutes after cataract surgery in an effort to detect hypotony (from presumed wound leakage).CONTAMINATION PREVENTION?
If vancomycin irrigation in the anterior chamber effectively reduced the incidence of endophthalmitis, I would expect surgeons to encounter far fewer culture-positive anterior chambers when vancomycin was added to the infusate. This is not the case. A study by Feys et al5 compared the rate of bacterial growth from two groups of patients, one that underwent phacoemulsification with no antibiotic in the irrigating fluid and another that had vancomycin (20µg/mL) in the infusate. In the control group, eight of 190 aqueous taps (4.2%) were positive for bacteria. In the vancomycin group, nine of 182 (4.9%) were positive. Interestingly, all isolates were vancomycin-sensitive, gram-positive organisms.THE HUMAN FACTOR
Antibiotics such as vancomycin and gentamicin are not formulated in the concentration needed for intracameral use, so the pharmacist, nurse, or physician must correctly dilute them. Because aminoglycosides can cause significant retinal toxicity (including macular infarction), their use should be avoided for intracameral irrigation if an error in dilution occurs. To reduce severe visual loss from endophthalmitis in one patient while avoiding ocular toxic effects in noninfected patients, Alfonso and Flynn6 estimated that antibiotics for intracameral use must be mixed correctly 2,700 times—a challenge for any center.COST
A standard bottle of vancomycin may cost the patient as much as $40 per dose if one bottle is used for each individual.6 Because an estimated 2 million cataract procedures are performed in the US each year, the potential cost would be $80 million per year if all surgeons used intracameral antibiotics. Certainly, the treatment of endophthalmitis is quite costly, but perhaps healthcare dollars should be spent on more effective, proven prophylactic measures.FOURTH-GENERATION FLUOROQUINOLONES
The FDA approved the fourth-generation fluoroquinolones moxifloxacin and gatifloxacin for the treatment of conjunctivitis, but their use in surgical prophylaxis is also important. Compared with prior generations of fluoroquinolones, these 8-methoxy agents provide greater gram-positive coverage, are able to overcome resistance to the second- and third-generation fluoroquinolones, and demonstrate improved penetration into the eye. A study7 performed at the University of Pittsburgh showed that topical moxifloxacin eradicated bacteria injected into the anterior segment of rabbits and thereby prevented the occurrence of endophthalmitis. This study represents the first time in ophthalmology that topical agents demonstrated excellent penetration at therapeutic levels in the anterior segment of the eye.COMPLICATED VERSUS UNCOMPLICATED SURGERY
In a study by Dickey et al,8 bacteria could be cultured from the anterior chamber after uncomplicated phacoemulsification up to 43% of the time. It is reassuring to know that none of the cases that had a positive anterior-chamber culture developed endophthalmitis, because this finding indicates that natural immune mechanisms are quite effective. Although the anterior chamber can clear a certain bacterial load without resultant infection, far fewer organisms in the vitreous gel will result in endophthalmitis. It therefore makes sense that, in complicated cataract surgery (in which the posterior capsule is ruptured), the risk of endophthalmitis increases significantly.9 In cases of a ruptured posterior capsule, I advocate a 7-day course of an oral fluoroquinolone, because the antibiotic achieves excellent penetration into the vitreous gel.FINAL THOUGHTS
I do not use intracameral antibiotics during cataract surgery because I do not believe that the practice is justified. No convincing studies to date have demonstrated the agents' effectiveness. Moreover, the Centers for Disease Control and Prevention issued guidelines in 1995 that specifically discourage the use of vancomycin for irrigation or routine surgical prophylaxis10 in an effort to prevent the emergence of multidrug-resistant organisms.
Of note, there has been a case report of endophthalmitis when vancomycin was used in the infusate.11 In this particular case, the organism isolated from the vitreous, coagulase-negative Staphylococcus species, was actually sensitive to vancomycin.
Fourth-generation fluoroquinolones achieve superb penetration into the anterior chamber. It is unnecessary to instill intracameral antibiotics, which may be toxic due to incorrect dilution.
Deepinder K. Dhaliwal, MD, is Associate Professor of Ophthalmology, Director of Refractive Surgery, and Director of Cornea/External Disease at the University of Pittsburgh School of Medicine, UPMC Eye Center. Dr. Dhaliwal may be reached at (412) 647-2214; firstname.lastname@example.org. Gritz DC, Cevallos AV, Smolin G, Whitcher JP Jr. Antibiotic supplementation of intraocular irrigating solutions. An in vitro model of antibacterial action. Ophthalmology. 1996;103:1204-1208.
2. Gills JP. Filters and antibiotics in irrigating solution for cataract surgery. J Cataract Refract Surg. 1991;17:385.
3. Gordon YJ. Vancomycin prophylaxis and emerging resistance: are ophthalmologists the villains? The heroes? Am J Ophthalmol. 2001;131:371-376.
4. Gills JP, Rowsey JJ. Bacterial endophthalmitis prophylaxis for cataract surgery. Ophthalmology. 2003;110:1668.
5. Feys J, Salvanet-Bouccara A, Emond JP, Dublanchet A. Vancomycin prophylaxis and intraocular contamination during cataract surgery. J Cataract Refract Surg. 1997;23:894-897.
6. Alfonso EC, Flynn HW Jr. Controversies in endophthalmitis prevention. The risk for emerging resistance to vancomycin. Arch Ophthalmol. 1995;113:1369-1370.
7. Kowalski RP, Romanowski EG, Mah FS, et al. Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model. Am J Ophthalmol. 2004;138:33-37.
8. Dickey JB, Thompson KD, Jay WM. Anterior chamber aspirate cultures after uncomplicated cataract surgery. Am J Ophthalmol. 1991;112:278-282.
9. Beyer TL, O'Donnell FE, Goncalves V, Singh R. Role of the posterior capsule in the prevention of postoperative bacterial endophthalmitis: experimental primate studies and clinical implications. Br J Ophthalmol. 1985;69:841-846.
10. Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance. Recommendations of the Hospital Infection Control Practices Advisory Committee. MMWR Morb Mortal Wkly Rep. 1995;44:1-13.
11. Townsend-Pico WA, Meyers SM, Langston RHS, Costin JA. Coagulase-negative Staphylococcus endophthalmitis after cataract surgery with intraocular vancomycin. Am J Ophthalmol. 1996;121:318-319.