Kill kinetics of advanced-generation fluoroquinolones compared in study

September 15, 2009

An in vitro kill kinetics study evaluated eradication of 18 human ocular Staphylococcus isolates by commercial formulations of gatifloxacin 0.3% (Zymar, Allergan) and moxifloxacin 0.5% (Vigamox, Alcon Laboratories). Gatifloxacin demonstrated superior activity, which may be attributed to the presence of benzalkonium chloride 0.005% in its formulation.

Key Points

Miami-Results from an in vitro study comparing Staphylococcus sp. kill rates for commercially available ophthalmic formulations of advanced-generation fluoroquinolones show that gatifloxacin 0.3% (Zymar, Allergan) consistently eradicated the bacteria significantly faster than moxifloxacin 0.5% (Vigamox, Alcon Laboratories).

The finding that benzalkonium chloride (BAK) 0.005% also had significant bactericidal efficacy suggests that the presence of this preservative in the gatifloxacin formulation may account for the superiority of gatifloxacin versus moxifloxacin, which is self-preserved.

However, human studies evaluating in vivo differences in antibacterial activity of the commercial products are needed to interpret the clinical relevance of these laboratory findings accurately, said Terrence P. O'Brien, MD, distinguished professor of ophthalmology and co-director, ocular microbiology laboratory, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami.

Aliquots were removed from the bacterial suspensions at 15, 30, and 60 minutes for assessment of bacterial viability. Statistical comparisons of antibacterial potency were made using data on mean log colony-forming units (CFU)/ml from the various assessment timepoints and showed the superiority of gatifloxacin versus moxifloxacin for reducing bacterial viability at all three intervals. Furthermore, 17 of the 18 isolates studied were completely eradicated by gatifloxacin at 60 minutes, with the majority (13/18, 72%) eradicated within 15 minutes. In contrast, at the end of the study period, moxifloxacin had completely eradicated only one (5.6%) of the 18 Staphylococcus isolates.

Prophylaxis

"Gatifloxacin and moxifloxacin are widely used as topical ophthalmic agents in an effort to prevent infection after cataract surgery, and rapid eradication of bacteria on the ocular surface is likely a critical asset for providing adequate protection," he said. "These studies suggest some important comparative differences in killing curve kinetics. However, we must be cautious about extrapolating the results of this in vitro study to predict clinical efficacy considering that the testing conditions do not account for factors present in the in vivo situation, including tear film dilutional effects of BAK and other pharmacodynamics."

Further clinical studies are warranted to compare the in vivo activity of these advanced-generation fluoroquinolones, he said.

"Nevertheless, based on clinical experience, it seems reasonable to conclude that both fluoroquinolone products are effective options for surgical prophylaxis if applied rationally in combination with an effective antiseptic agent," Dr. O'Brien said. "The advanced-generation fluoroquinolones would currently be considered superior alternatives to other classes of antibacterial agents, including the aminoglycosides, sulfa, or cephalosporins. Other pharmacodynamic attributes including penetration to target ocular tissues need to be considered in the ultimate selection of optimal antimicrobial agent(s)."

The study was performed recognizing that standard in vitro methods for determining antibacterial potency by assessing MIC values is typically performed using the raw antibacterial ingredient alone. In clinical use, however, antibacterial activity may be influenced by the presence of preservatives and other ingredients in the commercially available preparation.

"Fluoroquinolones exhibit concentration-dependent killing kinetics, and although the concentration of active ingredient is lower in the commercial preparation of gatifloxacin compared with moxifloxacin, 0.3% versus 0.5%, previous in vitro studies determining MIC values have shown that the addition of BAK augments the potency of gatifloxacin and moxifloxacin against ocular pathogens," Dr. O'Brien said.

For the kill kinetics study, the mean initial load of the bacterial inoculum was 5.45 log CFU/ml. Suspensions inoculated with non-bacteriostatic saline showed no evidence of bacterial eradication. However, exposure to BAK 0.005% alone achieved a significant reduction in bacterial load by 60 minutes (mean 3.80 log CFU/ml).

Mean recovered bacterial counts were consistently significantly lower with gatifloxacin versus moxifloxacin at all time points: 0.47 versus 4.55 CFU/ml, respectively, at 15 minutes, 0.07 versus 3.82 CFU/ml, respectively, at 30 minutes, and 0.00 versus 2.75 CFU/ml, respectively, at 60 minutes (p <0.005 for all comparisons). Complete eradication of 10 of 13 S aureus isolates and 3 of 5 CNS isolates was achieved within 15 minutes after gatifloxacin inoculation. Four of the five remaining isolates were completely eradicated by gatifloxacin by 30 minutes, and the fifth isolate, a strain of S aureus, was completely eradicated by 60 minutes. The single isolate eradicated by moxifloxacin was a CNS strain and eradication was not documented until 60 minutes.