Investigating Fourth-Generation Fluoroquinolones
BY LEO SEMES, OD, FAAO
Many have touted fourth-generation fluoroquinolones as the greatest thing since peanut butter. We've all seen the flurry of information surrounding Vigamox (0.5% moxifloxicin, Alcon) and Zymar (0.3% gatifloxicin, Allergan), which received approval in 2003. Unfortunately, all the hype following their introduction has made comparison difficult. Following are my thoughts.
Regardless of generation, fluoroquinolones are man-made antibiotics, meaning that bacteria exposed to them can survive (become resistant) only if they undergo mutations. That's to say no naturally resistant strains exist.
Researchers developed the newest class of antibiotics to greatly minimize resistance. Both moxifloxicin and gatifloxicin target two bacterial enzymes: DNA gryase and topoisomerase IV. Because of the dual targeting, bacteria must undergo two sponta neous mutations to become resistant. This significantly lowers the likelihood of resistance.
Bridging the Generation Gaps
Many are confused by what "generation" actually means. This has arisen partly from a disparity between systemic and topical applications.
Third-generation fluoroquinolones retain expanded Gram-negative and atypical intracellular activity, but have improved Gram-positive coverage. Fourth-generation fluoroquinolones improve Gram-positive coverage and gain anaerobic coverage. So, confusion reigns.
Researchers developed newer generations of fluoroquinolones in response to bacterial resistance to earlier generations.
Studying the New Generation
Results of recent studies suggest that both moxifloxicin and gatifloxicin have significant activity against bacteria that are resistant to third-generation fluoroquinolones and atypical mycobacteria. The package inserts of both products list FDA approval for conjunctivitis. Additional applications may include cataract and refractive surgical prophylaxis and treating bacterial keratitis.
But the two differ in their strengths, and some studies used non-commercial concentrations while others used data from laboratory and animal studies. This further clouds the issue of which fluoroquinolone practitioners should choose, regardless of "generation."
Perhaps clinicians should determine generation primarily by spectrum of coverage. This would place Quixin (0.5% levofloxicin, Santen; Iquix [1.5% levofloxacin] has just received FDA approval) in the fourth generation. Spectrum of coverage may be a better index of efficacy and may offer guidelines for clinical application.
The jury's still out regarding which fourth-generation fluoroquinolone will emerge as the magic bullet having the broadest spectrum of coverage, best penetration, best minimum inhibitory concentrations and most favorable resistance profile (the last of these is probably the most significant). The debates will rage over concentration, preservative, pH, solubility, application for surface vs. internal infections, etc. But the message is that clinicians should switch to the fourth-generation fluoroquinolones.
While bacteria will continue to become resistant to newer antibiotics and researchers will continually develop newer generations of fluoroquinolones, recognize that antibiotics have up to a 10-year life span. It won't be long before we see resistance in the ophthalmic realm. Our best defense is to adopt the newer fluoroquinolones to fight infection and preserve their integrity to bacterial resistance.
Dr. Semes is an associate professor at the University of Alabama at Birmingham School of Optometry.