Clinician judgment necessary if using new fluoroquinolones

Chicago-Evidence of a rising incidence of acute endophthalmitis postcataract surgery has intensified attention regarding the role of antibiotic prophylaxis, but the jury is still out on the efficacy of topical and intracameral therapy for reducing the risk of this sight-threatening infection, said Robert W. Snyder, MD, PhD, at the American Academy of Ophthalmology annual meeting.

"The rationale for using antibiotics is to eradicate ocular surface pathogens so as to prevent intraocular inoculation as well as to kill any microorganisms that gain entry into the eye. However, there are no well-designed, prospective clinical trials proving the efficacy of antibiotic prophylaxis strategies. Therefore, surgeons are left to consider available evidence carefully relating to formulation characteristics, bioavailability, and in vitro microbial sensitivity in order to guide their clinical choices," said Dr. Snyder, an ophthalmologist in private practice, and professor of biomedical sciences, University of Arizona, Tucson.

Reviewing some of the pertinent studies, Dr. Snyder noted that one of the earliest suggestions favoring the use of antibiotic prophylaxis emerged in a 1979 paper by Christy and Sommer. The pioneering work of Dr. Norval Christy reported that subconjunctival plus topical antibiotics decreased the incidence of endophthalmitis by 72% in a series of about 46,000 cataract operations, which he performed in Pakistan. In 2002 the methods of that study were criticized in a major literature review undertaken by Ciulla and colleagues. They concluded that all prophylactic techniques involving antibiotic use received the lowest rating in a three-tiered system used to grade importance to clinical outcome.

The introduction of the fourth-generation fluoroquinolone antibiotics, moxifloxacin 0.5% (Vigamox, Alcon Laboratories) and gatifloxacin 0.3% (Zymar, Allergan), has been accompanied by a plethora of publications reporting on their pharmacokinetics profiles and microbiologic spectrums of activity.

"These papers are intended to tout the relative benefits of these agents and many have been supported by the pharmaceutical manufacturers," Dr. Snyder observed.

In vitro findings

In vitro susceptibility studies from the Campbell Laboratory at the University of Pittsburgh show that by 2001, all endophthalmitis clinical isolates studied were uniformly resistant to the third-generation fluoroquinolones, ofloxacin (Ocuflox, Allergan) and ciprofloxacin (Ciloxan, Alcon). However, analyses of antibiotic susceptibility of gram-positive endophthalmitis and keratitis isolates showed moxifloxacin and gatifloxacin offered the opportunity to overcome low-level resistance as often seen against the "third-generation ciprofloxacin and ofloxacin."

New information suggests formulation with benzalkonium chloride (BAK) may play a role in antibacterial efficacy of topical antibiotics preparations. In another study from the Campbell Laboratory, Kowalski and colleagues recently reported 0.005% BAK rapidly eradicated Staphylococcus aureus.

"Whether or not the results of this in vitro study can be extrapolated to the ocular surface is unknown, but it suggests that adding BAK will result in more effective bacterial killing with faster eradication of bacteria and is of interest because gatifloxacin is formulated with BAK while moxifloxacin contains no preservatives," Dr. Snyder observed.

Eradication of any pathogens that gain entry into the eye is also considered an important component of effective antibiotic prophylaxis, and it is relevant to consider penetration of topical antibiotics into the anterior chamber. Both gatifloxacin and moxifloxacin offer reasonable penetration with typical clinical dosing regimens, although aqueous concentrations achieved are significantly higher after application of moxifloxacin versus gatifloxacin. That difference can be explained in part by the higher concentration of moxifloxacin compared with gatifloxacin in the commercially available preparations, 0.5% versus 0.3%, respectively.

Results from a rabbit study demonstrate that topical prophylaxis with moxifloxacin is effective for preventing endophthalmitis caused by S aureus.

However, Dr. Snyder pointed out that the findings from that animal model may not necessarily be extrapolated to humans.

"We do not yet understand pharmokinetics in the anterior chamber from antibiotics placed onto the ocular surface," he said.