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Dermot McGrath in Rome
Dr Colin said the penetration of levofloxacin 0.5% eye drops into the anterior chamber compared favourably with another third-generation ophthalmic fluoroquinolone, ciprofloxacin 0.3%, for patients undergoing standard cataract surgery. In the prospective, randomised study carried out from October 2001 to March 2002 in Bordeaux, France, 60 patients received four drops of either levofloxacin or ciprofloxacin eye drops within one hour (at 60, 30, 15 and 0 minutes) prior to elective cataract surgery. Researchers drew aqueous humour samples of at least 50 microlitres from the anterior chamber at the beginning of the cataract extraction and measured the concentration of the fluoroquinolone in the anterior chamber using high performance liquid chromatography (HPLC). The results showed that the mean concentration of levofloxacin (917.3 ng/ml, SD 656.3) in the aqueous humour was much higher than that of ciprofloxacin (118.2 ng/ml, SD 113.4). The difference was highly statistically significant. Because of its heightened solubility, levofloxacin can be formulated at a high concentration (0.5%). “High solubility translates as high penetration into the eye, and, since there is a direct relationship between antibacterial action and concentration at the site, it shows high antimicrobial activity,” Dr Colin said. The fluoroquinolone exhibits bactericidal activity mainly through interference with the activity of bacterial DNA gyrase. As concentration-dependent killers, fluoroquinolone antibiotics must reach the minimum inhibitory concentration (MIC) to work effectively. The median MIC90 for staphylococcus epidermis is 780 ng/ml for levofloxacin and 1170 ng/ml for ciprofloxacin. Although large inter-individual variations existed, Dr Colin said both the mean and median levels of levofloxacin in the anterior chamber were above the MIC90 median, while those for ciprofloxacin were below the target value. For the staphylococcus aureus MIC90 values, levofloxacin reached values which were presumed effective, while ciprofloxacin did not. Dr Colin said the results mirrored those of an earlier study conducted by Hans-Reinhard Koch MD in Bonn, Germany which compared the penetration of levofloxacin with another fluoroquinolone, ofloxacin, into the anterior chamber. Prof Koch also found that topical application of levofloxacin achieved very high concentration levels in the aqueous humour and typically achieved intraocular levels above the MICs for common pathogens. Dr Colin concluded that levofloxacin fulfilled the criteria for a high-performance antimicrobial agent - it offered efficient bactericidal activity against a broad spectrum of gram-positive and gram-negative organisms, low toxicity, rapid onset of action and a long duration. He added that there were no adverse events arising from the study, except the type of occurrences normally expected after cataract surgery. Dr Colin’s conclusions were echoed in another recent clinical trial in the US, which tested the 0.5% levofloxacin ophthalmic solution, compared to the 0.3% ofloxacin, for the treatment of bacterial conjunctivitis. In a prospective, randomised, double-masked, multicentre study involving 208 patients, the microbial eradication rates were found to be significantly greater in the 0.5% levofloxacin treatment group, compared with the 0.3% ofloxacin group at both the final visit (89% vs 80%, P=0.034) and at end point (90% vs 81%; P=0.038). Treatment with 0.5% levofloxacin was significantly more effective in resolving photophobia than 0.3% ofloxacin treatment (94% vs 73%, P=0.006). The authors of the study, published in Ophthalmology, concluded that although clinical cure rates in the 0.5% levofloxacin and 0.3% ofloxacin treatment groups were similar, a five-day treatment regimen with 0.5% levofloxacin achieved microbial eradication rates which were statistically superior to those attained with 0.3% ofloxacin. Despite the higher concentration of active drug in 0.5% levofloxacin, compared to 0.3% ofloxacin, there was no difference between treatment groups in the incidence of treatment-related adverse events. The study was entitled “A phase III clinical trial of 0.5% levofloxacin ophthalmic solution versus 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis.” (Schwab IR, Friedlaender M, McCulley J, Lichtenstein SJ, Moran CT, Ophthalmology 2003 March; 110 (3):457-465). Joseph Colin MD
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