Comparing fluoroquinolones: Is faster better?

ByRandall J. Olson, MD

BAK is a powerful antifungal and antibacterial preservative with broad-spectrum activity against microorganisms.
—Randall J. Olson, MD

Randall J. Olson, MD [photo]

Newer generation fluoroquinolones are effective topical antibiotics with low levels of minimum inhibitory concentrations (MICs). Although data on newer generation fluoroquinolones demonstrate better efficacy against gram-positive organisms compared with other fluoroquinolones,¹ existing MIC data have limitations. MIC susceptibility tables are based on systemic break points; less drug may be needed topically. Another limitation is that analyses of MICs frequently involve a single antimicrobial agent. Additionally, ophthalmic antimicrobial solutions contain a mix of ingredients, such as benzalkonium chloride (BAK), and the mixture may be more effective than the active ingredient alone.

BAK is a powerful antifungal and antibacterial preservative with broad-spectrum activity against microorganisms. Comparative data of MICs of gatifloxacin with and without BAK demonstrate that the solution with BAK has a significantly lower MIC (Figure 1).² The additive effect of BAK is not intraocular but superficial, as it eliminates superficial resistant bacteria, demonstrates a clinical effect on conjunctivitis and corneal ulcers and minimizes bacterial load prior to surgery.

Comparative MICs of gatifloxacin with and without BAK

Figure 1. Comparative data show that gatifloxacin with BAK has a lower MIC for a number of organisms than gatifloxacin without BAK.

Source: Olson RJ. Adapted from Invest Ophthalmol Vis Sci. 2005;46:E-abstract 4880.

BAK speeds eradication

BAK also affects newer generation killing curves. Surgeons may infer that commercial gatifloxacin has a disadvantage when compared with moxifloxacin because commercial gatifloxacin is marketed at 0.3% solution and moxifloxacin is marketed at 0.5% solution. Studies demonstrate, however, that gatifloxacin with BAK is more effective against common pathogens and speed of kill is dramatically different compared with moxifloxacin.³ Ilker Eser, MD, and colleagues showed that gatifloxacin 0.3% with BAK is more effective against all strains of Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus hominis than moxifloxacin 0.5% (Figures 2, 3).³ Eradication rates against several strains of Staphylococcus also demonstrated the effectiveness of gatifloxacin with BAK. Gatifloxacin with BAK reduces colony counts within 15 to 60 minutes, according to the data.³ When compared with gatifloxacin alone and moxifloxacin, gatifloxacin with BAK has the lowest MICs and is the most effective against common ocular pathogens (Figure 4).² Gatifloxacin with BAK is also the most effective against Pseudomonas aeruginosa, according to the same study.

In a series of comparative MICs of four fluoroquinolones against clinical isolates of fluoroquinolone-resistant S. aureus, data demonstrated that gatifloxacin with BAK and moxifloxacin with BAK reduced resistance to significantly low levels.⁴ Comparative MICs of four fluoroquinolones against clinical isolates of methicillin-resistant S. aureus also showed that BAK markedly affects resistance levels, and gatifloxacin with BAK and moxifloxacin with BAK have significantly low levels of resistance.

In a recent study, Francis Mah, MD, and colleagues demonstrated that gatifloxacin with BAK is superior to gatifloxacin alone.⁵ Colony count data illustrate that gatifloxacin with BAK reduces colony counts, and the effect is not isolated to in vitro studies.

Efficacy of gatifloxacin with BAK and moxifloxacin against
all strains of S. aureus

Figure 2. Gatifloxacin with BAK was more effective against all strains of S. aureus than moxifloxacin.

Source: Olson RJ. Adapted from Cornea. In press.

Efficacy of gatifloxacin with BAK vs. moxifloxacin
against S. epidermidis and S. hominis

Figure 3. Gatifloxacin with BAK was more effective against all strains of S. epidermidis and S. hominis than moxifloxacin.

Source: Olson RJ. Adapted from Cornea. In press.

Efficacy of gatifloxacin and moxifloxacin against
common ocular pathogens

Figure 4. Gatifloxacin with BAK was shown to lower MICs against common ocular pathogens than moxifloxacin.

Source: Olson RJ. Adapted from Invest Ophthalmol Vis Sci. 2005;46:E-abstract 4880.

Further study necessary

Newer generation fluoroquinolones, such as gatifloxacin and moxifloxacin, are efficient antibiotics. In some cases, one antibiotic will be more effective than the other, depending on factors such as gram-negative or gram-positive coverage. Essentially, gatifloxacin and moxifloxacin are not significantly dissimilar. For minimizing bacterial load and superficial antibiosis, however, it appears that BAK dramatically lowers MICs, making even significantly resistant bacteria sensitive, and dramatically speeds up kill rates. More clinical data are necessary to fully expand on the recent findings that show BAK minimizes resistance.

References

Hsu VJ, Affeldt J, Blanton C. Streptococcus mitis corneal ulcer. Invest Ophthalmol Vis Sci. 2005;46: E-Abstract 2632.
Blondeau JM, Hedlin P, Borsos SD. The antimicrobial activity of gatifloxacin (GAT) with or without benzalkonium chloride (BAK) against ocular bacterial pathogens. Invest Ophthalmol Vis Sci. 2005;46:E-Abstract 4880.
Eser I, Hyon J, Hose S, O’Brien TP. Comparative antimicrobial efficacy of preserved and preservative-free topical fourth generation fluoroquinolones against various strains of Staphylococcus. Invest Ophthalmol Vis Sci. 2004;45:E-Abstract 4921.
Metzler K, Hansen GM, Hedlin P, et al. Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus. Int J Antimicrob Agents. 2004;24:161-167.
Romanowski EG, Mah FS, Yates KA, et al. The successful treatment of gatifloxacin-resistant Staphylococcus aureus keratitis with Zymar (gatifloxacin 0.3%) in a NZW rabbit model. Am J Ophthalmol. 2005;139:867-877.