The ESCRS study of the prophylaxis of postoperative endophthalmitis after cataract surgery1 created quite a stir among ophthalmologists. Finally, there was a prospective, randomized, placebo-controlled study demonstrating a benefit of intracameral antibiotics in preventing endophthalmitis. Specifically, the report showed that an intracameral injection of cefuroxime at the end of cataract surgery lowered the risk of endophthalmitis by a factor of five. This landmark study evaluated nearly 14,000 patients from 24 centers in nine European countries. Additional risk factors for endophthalmitis gleaned from the study included clear corneal wounds and silicone IOLs.2
Before we surgeons all instruct our surgical nurses to take 750 mg of cefuroxime powder and dilute it to a concentration of 1 mg/0.1 mL of balanced salt solution for our next cataract cases, we need to examine the study closely and understand its implications.
An animal study conducted at the University of Pittsburgh4 showed that topical moxifloxacin could prevent postoperative endophthalmitis in eyes that had been inoculated with Staphylococcus aureus. The eyes that did not receive topical moxifloxacin all developed endophthalmitis due to the number of organisms inoculated in the eye. None of the eyes that received topical moxifloxacin before and after inoculation developed endophthalmitis. This striking study illustrated just how powerful topical antibiotics can be in the prevention of endophthalmitis. It showed that a topical agent can penetrate the eye at a high enough concentration to reach therapeutic, bacteriocidal levels. It is unknown what the ESCRS study's results would have been had all patients received pre- and postoperative moxifloxacin or gatifloxacin.
An additional issue in regard to an antibiotic's safety is a patient's potential hypersensitivity to the drug. Someone who is allergic to a topical agent will typically have contact dermatitis or conjunctivitis but will not develop an anaphylactic reaction. Patients with hypersensitivity to an intracameral agent, such as cefuroxime, can actually develop systemic anaphylaxis with associated morbidity and possible mortality, as reported by Villada et al.8 They described a patient with a history of allergy to oral ampicillin who received 1 mg of cefuroxime intracamerally (the same concentration as used in the ESCRS study) at the conclusion of an uncomplicated phaco case. Five minutes later, the patient developed problems breathing and went into hypovolemic shock due to the anaphylactic reaction. Fortunately, the anesthesiologist was present in the recovery room and quickly administered intravenous methylprednisolone, ephedrine, 3 L of Ringer's lactate solution, and antihistamines. The patient recovered from this life-threatening allergic reaction in half an hour but was admitted to the hospital for observation. Referring to this case, Liu et al9 stated, "conceptually speaking, intracameral antibiotic administration in a patient with a history of antibiotic allergy is highly akin to the direct intravenous route of administration in terms of bioavailability, particularly in the face of a disrupted blood-aqueous barrier during phacoemulsification."
The rate of any hypersensitivity to a cephalosporin such as cefuroxime is reported to be 1 to 3.10 The rate of anaphylaxis with cephalosporins is reported to be 0.1 to 0.0001.11 With approximately 2.5 million cataract surgeries performed each year in the US, as many as 2,500 patients per year could potentially develop anaphylaxis if every case were performed according to the ESCRS study guidelines and each patient received intracameral cefuroxime. Montan and colleagues6 continue to use cefuroxime on a wide-scale basis in Sweden by pretreating patients with a history of anaphylaxis to this antibiotic with oral antihistamines. In the ESCRS study, patients were excluded if they were allergic to penicillins and cephalosporins. What if the patient has not been exposed to enough antibiotics, however, to realize a hypersensitivity exists?
SPECTRUM OF ACTIVITY
A study performed at the University of Pittsburgh showed that moxifloxacin and gatifloxacin provided higher susceptibility to Bacillus, Enterococcus, and gram-negative bacteria than cefuroxime using actual endophthalmitis isolates and equal susceptibility for Staphylococcus and Streptococcus strains. The researchers concluded that, in regard to the choice of an intracameral agent, fourth-generation fluoroquinolones might provide more broad-spectrum coverage of endophthalmitis-causing bacteria than cefuroxime.13
EFFICACY OF CEFUROXIME
A kinetics of kill study was performed with cefuroxime against staphylococcal ocular isolates.15 It showed that less than one log kill was achieved in 3 hours. The researchers contrasted this result to the kinetics of kill of moxifloxacin, which showed a greater than three log kill (> 99.9) after less than 2 hours. This difference may explain the development of endophthalmitis secondary to a cefuroxime-susceptible strain of S. aureus in a patient who received intracameral cefuroxime at the end of surgery.11
There are several factors we need to keep in mind before we change our practice patterns in 2007. First, certain groups of patients were ineligible to participate in the ESCRS study, including nursing home patients. In addition, cefuroxime is a slow, time-dependent killer that is ineffective against MRSA, Pseudomonas, and some Enterococcus species. There are several issues of safety with this agent, including reports of severe anaphylaxis. Finally, ESCRS study patients did not receive adjunctive topical fourth-generation fluoroquinolones, which have an improved spectrum of coverage, higher potency, delayed antibiotic resistance, and better tissue penetration compared with the third-generation fluoroquinolone used in the ESCRS study.
Deepinder K. Dhaliwal, MD, is Associate Professor, University of Pittsburgh School of Medicine; Director, Cornea & External Disease Service, UPMC Eye Center; Director, Refractive Surgery Service, UPMC Eye Center; and Medical Director, UPMC Laser/Aesthetic Center, all in Pittsburgh. Dr. Dhaliwal may be reached at (412) 647-2214; firstname.lastname@example.org.