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Levofloxacin 1.5% (Iquix, Santen/Vistakon) is the only newer generation fluoroquinolone approved for the treatment of bacterial corneal ulcers. Extensive research indicates levofloxacin has maintained potent broad-spectrum activity against important ocular pathogens and that the 1.5% formulation offers excellent pharmacokinetics and safety profiles.
New York-Levofloxacin 1.5% (Iquix, Santen; co-marketed by Vistakon) is a valuable addition to the therapeutic armamentarium for treatment of bacterial corneal ulcers, said Penny Asbell, MD.
In this newer-generation formulation of levofloxacin, the concentration of active ingredient is 3- to 5-fold higher than that of any other commercially available fluoroquinolone products, and that has key importance in treating serious corneal infections. Levofloxacin 1.5% reportedly provides potent broad-spectrum activity against important pathogens along with excellent penetration characteristics, and it is safe and well tolerated.
"For all of these reasons, it is an excellent option that ophthalmologists can reach for off-the-shelf to begin immediate empiric therapy of corneal ulcers," said Dr. Asbell, professor of ophthalmology, and director of cornea services, external disease, and refractive surgery, Mount Sinai School of Medicine, New York.
Although levofloxacin is sometimes characterized as a third-generation fluoroquinolone and differentiated from moxifloxacin and gatifloxacin, which are referred to as fourth-generation fluoroquinolones, Dr. Asbell noted that classification is only accurate if the definitions are based on the timing of product market introduction. If fluoroquinolone generations are defined based on mechanism of action and spectrum of antimicrobial activity, levofloxacin, moxifloxacin, and gatifloxacin would all be considered within the same category.
"Levofloxacin, like moxifloxacin and gatifloxacin, has a dual mechanism of antibacterial activity involving inhibition of both bacterial topoisomerase IV and DNA gyrase. As a result, these fluoroquinolones are less susceptible to resistance emergence and provide a broader spectrum of activity against gram-negative and gram-positive organisms compared with earlier generation fluoroquinolones, such as ciprofloxacin," she explained.
Recent data from national antibiotic surveillance programs also show that levofloxacin, moxifloxacin, and gatifloxacin mirror each other closely in terms of their potency against common ocular pathogens. In Tracking Resistance in the United States Today (TRUST), which was started in 1996 when levofloxacin first became available for systemic use, levofloxacin, moxifloxacin, and gatifloxacin are tracking similarly in terms of patterns of resistance even though levofloxacin has been available for several years longer than moxifloxacin and gatifloxacin.
"These findings are replicated in Ocular TRUST, a surveillance program that monitors in vitro susceptibility of clinical ocular isolates. For example, recent data show that about 93% of methicillin-sensitive Staphylococcus aureus remain sensitive to all three of these newer generation fluoroquinolones whereas none performed well against methicillin-resistant S. aureus. The take-home message is that all three fluoroquinolones have good broad-spectrum activity, but it is important to remember that none will eradicate every infection," Dr. Asbell said.
She also observed that while some published studies have reported emerging resistance to levofloxacin, most of those are based on testing of a small number of isolates. Therefore, their results should not be generalized to broader populations. Recent consensus guidelines for monitoring antimicrobial resistance suggest that a minimum of 30 isolates for any specific strain be tested to provide interpretable results, noted Dr. Asbell.
"Data from small studies are likely accurate for the specific reporting institution. However, in contrast to findings from national surveillance programs, they may be skewed because of the limited number of isolates evaluated and should not be considered representative of resistance patterns across the United States," Dr. Asbell said.