Latest fluoroquinolones have higher potency

WAILEA, Hawaii — The minimum inhibitory concentrations of the newest generation of ophthalmic fluoroquinolones are significantly lower than those of previous generations, indicating higher potency, speakers here said. Laboratory and clinical test results with these fluoroquinolones were the subject of an Allergan-sponsored breakfast and an Alcon-sponsored breakfast here at Hawaiian Eye 2006.

Francis S. Mah, MD, conducted in vitro tests of gatifloxacin 0.3% preserved with benzalkonium chloride (BAK) and moxifloxacin 0.5% self-preserved. He said both these fluoroquinolones have a broad spectrum with improved activity against gram-positive bacteria compared to earlier-generation fluoroquinolones, as well as retaining the earlier generation’s activity against gram-negative bacteria.

“Certain pathogens that are resistant to previous generation fluoroquinolones are susceptible to the fourth-generation drugs,” he said.

In a study, Dr. Mah compared formulations of both of these fluoroquinolones, both with and without BAK, to determine whether the BAK has the ability to potentiate the effect of the antibiotic. He compared the four antibiotic formulations to BAK as a standalone antiseptic agent.

Comparing the results of time-to-kill tests, Dr. Mah found that BAK complemented gatifloxacin 0.3% in eliminating certain gram-positive bacteria, such as Staphylococcusaureus, and coagulase-negative Staph species, but it had no effect on gram-negative Pseudomonas aeruginosa bacteria.

In another presentation, Randall J. Olson, MD, said BAK activity is likely a superficial effect on the ocular surface, but perhaps not an intraocular effect due to its inability to effectively penetrate the cornea. This effect of BAK being additive to the antibiotic’s effect would be helpful in minimizing the bacterial load on the ocular surface prior to surgery, he suggested.

The current standards of comparing bacterial susceptibility to antibiotics is based upon systemic serum standards, which may not be directly applicable to ophthalmic use, Dr. Mah said, and therefore the bacterial resistance may be overstated. He gave an example of a strain of methicillin-resistant Staph aureus (MRSA) that was shown to have in vitro resistance to gatifloxacin in the laboratory, but with frequent ocular dosing, the same strain of MRSA in a clinical setting was effectively killed using the same antibiotic. He suggested that ophthalmologists need new methods to evaluate the clinical efficacy of topical antibiotics.

Dr. Olson said if two commercially available ophthalmic fluoroquinolones are compared, their commercial formulation, including preservatives, should be used for testing. For some organisms, he said, BAK may help to lower the minimum inhibitory concentrations (MICs) and therefore improve the kill rate of susceptible pathogens.

Dr. Mah suggested that ophthalmologists should look at the minimal bactericidal concentration, or MBC, which he said tends to be three to four times the MIC. He said this number better reflects the killing power of an antibiotic. Levels of the drug in tissue must be above the MIC; any level below that is sub-inhibitory and ineffective for bacterial eradication, he said.

Dr. Mah said an in vivo study of moxifloxacin showed its ability to eradicate endophthalmitis-causing organisms in rabbit eyes. He noted that the use of moxifloxacin in the perioperative period for prophylaxis against endophthalmitis is an off-label indication for the drug.

Terry Kim, MD, presented results of a study evaluating the corneal concentrations of the newer fluoroquinolones in patients undergoing corneal transplantation. He said moxifloxacin achieved significantly higher corneal concentrations than gatifloxacin, “easily achieving levels above the MIC of major bacterial isolates.”

By Uday Devgan, MD, FACS, OSN Cataract Surgery Section Member and OSN Back to Basics column editor.