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A study evaluating eradication of methicillin-resistant Staphylococcus aureus (MRSA) by fluoroquinolones shows that the commercially available preparation of gatifloxacin 0.3% (Zymar, Allergan) has superior bactericidal activity compared with the commercially available preparation of moxifloxacin 0.5% (Vigamox, Alcon). Gatifloxacin was more active than moxifloxacin alone, and its activity was enhanced by the presence of the preservative benzalkonium chloride.
"In previous in vitro studies determining minimum inhibitory concentration values, we found the activity of gatifloxacin against multidrug-resistant gram-positive organisms, including MRSA, was significantly enhanced by benzalkonium chloride [BAK], which is present as a preservative in the commercially available ophthalmic preparation of gatifloxacin," said Dr. Blondeau, head of clinical microbiology, Royal University Hospital and University of Saskatchewan, Saskatoon. "In addition, the activity of the combination was significantly greater than that of moxifloxacin. The current study goes one step further in evaluating the potency of these fluoroquinolones by investigating the rate and extent of their activity for eradicating MRSA.
"The results show gatifloxacin alone outperforms moxifloxacin both in speed and magnitude of bacterial eradication, and the activity of gatifloxacin is further enhanced by the presence of BAK," he continued. "The findings likely have clinical implications considering that outcomes of antimicrobial treatment are linked to achieving bacterial eradication and in ophthalmology, where the duration of drug exposure to effective concentrations may be short, rapid reduction of the bacterial load is an important benefit."
The concentrations were selected to replicate those that would be achieved with conventional dosing using the commercially available preparations of each fluoroquinolone. Bactericidal activity was evaluated by determining log10 reductions in bacterial counts and percentage of killed bacteria after 5, 25, and 120 minutes.
At 5 minutes, 39% of bacteria were eradicated by gatifloxacin 300 µg/ml (1.0 log reduction), and the rate increased to 70% (0.54 log reduction) when gatifloxacin was combined with BAK 15 µg/ml whether using the raw materials or proprietary gatifloxacin. At 25 minutes, incubation of bacteria with either gatifloxacin 300 µg/ml plus BAK 15 µg/ml or proprietary gatifloxacin resulted in a 91% kill rate (1.4 log reduction), and with both combinations of gatifloxacin plus BAK, 99% of bacteria were killed at 120 minutes (~2.7 log reduction). Compared with gatifloxacin 300 µg/ml by itself, the presence of BAK with gatifloxacin enhanced the kill rates at all time points, whereas the combination of gatifloxacin 300 µg/ml plus BAK 15 µg/ml had comparable bactericidal activity compared with gatifloxacin 600 µg/ml.
Only 32% of bacteria were killed after 5 minutes of incubation with proprietary moxifloxacin (0.37 log reduction), and the eradication rate increased to only 34% at 25 minutes (0.60 log reduction) and to 52% at 120 minutes (0.68 log reduction).