Rx Perspective
Assessing Antibiotics Intelligently
Demand these key data so you can make effective choices.

BY JAMES MCCULLEY, M.D., F.A.C.S., F.R.C. OPHTH.

Are you sure you're prescribing the correct antibiotic for your patients? Are you basing your prophylaxis or treatment decisions on sound clinical data? Pondering these questions is important as new antibiotics, specifically moxifloxacin and gatifloxacin, progress through development.

Unfortunately, ophthalmologists have fallen behind infectious disease experts and others in assessing antibiotics. Besides clinical trial data, the latter use standard in vitro microbiological tests to help them determine how best to use antibiotics.

To make sure that you have the correct data on which to base clinical decision making, demand that pharmaceutical firms provide in vitro test information to help you evaluate an antibiotic. Specifically, you need to ask for data about efficacy and toxicity.

Because the FDA doesn't require this data for drug approval, pharmaceutical firms haven't done a comprehensive job of collecting it. However, calls for this data are beginning to change that.

WHAT YOU NEED TO KNOW ABOUT EFFICACY

Three tests can help you gauge efficacy, so ask pharmaceutical firms to provide these values for their antibiotics:

Therapeutic index/inhibitory quotient (IQ). The IQ involves a simple fraction. The numerator represents the achievable concentration of antibiotic in the tissue in question.

The denominator is the MIC90 of an antibiotic against a bacterium. The MIC90 refers to the concentration of antibiotic that is exposed to a defined number of bacteria so that 90% of the organisms are inhibited from growth. Both the numerator and denominator are available from the medical literature or pharmaceutical firms.

For example, to gauge an antibiotic's efficacy against Pseudomonas on the ocular surface, you would place the concentration of antibiotic achieved on the ocular surface in the numerator and the MIC90 of Pseudomonas in the denominator. If the concentration on the ocular surface exceeds the MIC90, then the antibiotic would be effective in inhibiting 90% of the organism on the ocular surface. That is, if the resulting number ­ the IQ -- from solving the fraction is 1 or greater, the level is therapeutic; if it's less than 1, the level is not therapeutic.

Time-kill curve (TKC). This tells how quickly an antibiotic will kill a bacterium once it comes in contact with it. In prophylaxis, the TKC lets you know how far ahead of a planned surgery you should give an antibiotic.

Ciprofloxacin, for instance, typically kills bacteria within minutes, but ofloxacin requires many hours. So if you need to prophylax a patient prior to surgery and want to start the antibiotic when the patient arrives in the day surgery unit, you would choose ciprofloxacin. You would want to start ofloxacin, on the other hand, a day or more before surgery.

In treating infections, as opposed to prophylaxis, the more rapidly an antibiotic kills an organism, the less damage the tissue will suffer.

Post-antibiotic effect (PAE). Significant mainly for prophylaxis, the PAE measures the time it takes bacteria to recover from a nonlethal exposure to an antibiotic.

In cataract surgery, for instance, the patient's ocular surface or lid margins are the source of most organisms causing endophthalmitis. After surgery, you can recover bacteria from the aqueous humor in 10% to 45% of patients. But if the bacteria have been influenced by an antibiotic with a long PAE, the patient's natural defenses will have much longer to clear the bacteria from the eye.

The PAE is one reason why only 7 in 10,000 patients develop endophthalmitis when 10% to 45% of them have recoverable bacteria from the aqueous humor at the conclusion of cataract surgery.

INFORMATION ABOUT TOXICITY

Information about toxicity is also important in your antibiotic decision making. Toxicity tests can involve lab studies, as well as animal and human studies. The lab studies usually assess toxicity by exposing corneal epithelium or keratocytes in tissue cultures to appropriate concentrations of antibiotic.

MAKING SOPHISTICATED CHOICES

Ophthalmologists must become more sophisticated in assessing antibiotic effectiveness. The IQ, TKC and PAE will help. For instance, when I studied two widely used fluoroquinolones, the data on IQ, TKC, and PAE revealed that one agent would be preferred for prophylaxis immediately prior to surgery.

Companies are starting to provide more in vitro data for antibiotics. At this time, fairly complete data exist for both IQ and TKC for two of the topical fluoroquinolones on the market.

With gatifloxacin and moxifloxacin in development, you need to demand this data for these and all new antibiotics. Only with this information can you intelligently select which antibiotic to use in which situation, rather than being swayed only by well-funded marketing campaigns.

Dr. McCulley is professor and chairman of the Department of Ophthalmology at the University of Texas Southwestern Medical School in Dallas.