Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients

Purpose: To measure the achievable perioperative aqueous concentration of the commercially available topically administered fourth generation fluoroquinolones, moxifloxacin 0.5% ophthalmic solution, and gatifloxacin 0.3% ophthalmic solution, and to correlate this concentration with the agents' biological efficacy in the aqueous humor of patients undergoing routine cataract surgery. Design: Prospective, randomized, parallel, double-masked, clinical trial. Participants: Fifty patients undergoing cataract extraction. Methods: Patients (n = 25) were given perioperative topical moxifloxacin 0.5% or topical gatifloxacin 0.3% (n = 25). One drop of antibiotic was administered every 10 minutes for 4 doses beginning 1 hour prior to surgery. Aqueous humor was sampled via paracentesis and antibiotic concentrations were determined using validated high performance liquid chromatography (HPLC) procedures. Dilution analyses were performed to determine the biological efficacy of the agents in the aqueous against Staphylococcus epidermidis, the most common cause of postcataract endophthalmitis. Main Outcome Measures: Aqueous humor antibiotic concentrations were measured using HPLC and microdilution bioassay techniques. Biological activity was measured as minimal inhibitory dilution and minimal bactericidal dilution. Results: Aqueous humor concentrations for moxifloxacin via HPLC analysis were 1.80 (+/- 1.21) mu g/ml, whereas those for gatifloxacin were 0.48 (+/- 0.34) mu g/ml. This 3.8-fold difference in aqueous humor antibiotic concentrations was statistically significant (P = 0.00003). Similarly, the biological dilution analysis of the aqueous humor samples showed that moxifloxacin attained an estimated activity of 2.1 mu g/ml, whereas the gatifloxacin activity was approximately 0.4 mu g/ml, which represented a 4.9-fold difference. Conclusions: This study demonstrated that after topically administered perioperative antibiotics with cataract surgery, moxifloxacin 0.5% ophthalmic solution achieved a statistically significantly higher concentration in aqueous humor compared with gatifloxacin (P = 0.00003). Results from the broth dilution analysis showed that moxifloxacin 0.5% was biologically more active against S. epidermidis than gatifloxacin 0.3% in aqueous humor after topical application. There were no adverse events reported, and incision wounds healed quickly and as expected.