Vitreal penetration of oral moxifloxacin in humans

PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral administration. DESIGN: Prospective, nonrandomized clinical series. METHODS: Twenty-four patients (mean age = 62.8 years) undergoing elective pars plana vitrectomy were assigned to a dosing group: control (n = 3), which received no medication; single-dose (n = 11), which received one 400 mg oral dose of moxifloxacin 3 hours before surgery; and five-dose (n = 10), which received one 400 mg dose on each of the 4 days preceding surgery and a fifth dose 3 hours before surgery. Vitreous samples were obtained and analyzed. RESULTS: Control, below quantifiable levels; single-dose, 0.572 +/- 0.239 microg/mL; and five-dose, 1.200 +/- 0.645 microg/mL. CONCLUSIONS: Five doses of oral moxifloxacin lead to higher intravitreal drug concentrations than single-dose administration. Both regimens, however, achieve levels that exceed the MIC90 of many bacteria implicated in postoperative endophthalmitis.     

Absorption of topical moxifloxacin ophthalmic solution into human aqueous humor

PURPOSE: To investigate the absorption of moxifloxacin into human aqueous humor after administration of moxifloxacin hydrochloride ophthalmic solution, 0.5% as base. METHODS: Cataract patients were randomly allocated to receive 1 drop every 15 minutes for 4 doses before surgery (group 1) or 1 drop 4 times per day on the day before surgery plus the same preoperative regimen as group 1 (group 2). The last dose was administered 0.25, 0.50, 1, 2, or 3 hours before aqueous humor sampling. Samples from 30 patients per group were analyzed by a validated HPLC/MS/MS method. RESULTS: For group 1, the mean +/- SD C(max) was 1.50 +/- 0.75 microg/mL and occurred at 0.5 hour after dosing. The mean C(max) for group 2 was 1.74 +/- 0.66 microg/mL and was reached at 1 to 2 hours. Mean AUC(0-3h) for groups 1 and 2 were 3.16 +/- 0.29 and 4.41 +/- 0.48 microg.h/mL, respectively. The difference in AUC(0-3h) was statistically significant (P = 0.04), but the difference in Cmax was not. CONCLUSIONS: Topical moxifloxacin was well absorbed. Maximum moxifloxacin concentrations were approximately 30 times higher than the median MICs for common pathogens in bacterial endophthalmitis, indicating that either regimen may provide sufficient concentrations to prevent postoperative endophthalmitis.     

Vitreal penetration of oral and topical moxifloxacin in humans

PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral and topical administration. DESIGN: Prospective, nonrandomized clinical trial. METHODS: Twenty-four patients were assigned to one of four dosing groups: control (n = 3), which received no medication; oral (n = 8), which received two 400 mg oral doses of moxifloxacin before surgery; topical (n = 8), which received one drop of topical moxifloxacin 0.5% every 15 minutes for the hour preceding surgery; and combined (n = 5), which received two 400 mg oral doses and one drop of topical moxifloxacin 0.5% hourly for 18 hours prior to surgery. Vitreous samples were obtained and analyzed. RESULTS: Control, below quantifiable levels; oral, 1.553 +/- 0.33 microg/ml; topical, 0.027 microg/ml; and combined, 2.219 +/- 0.71 microg/ml. One topical patient developed postoperative endophthalmitis. CONCLUSIONS: In contrast to topical moxifloxacin, oral moxifloxacin achieves significant levels in the noninflamed human vitreous.     

Aqueous and vitreous penetration of levofloxacin after topical and/or oral administration

PURPOSE: To investigate the aqueous and vitreous penetration of levofloxacin, the drug was administered topically and/or orally to patients undergoing vitrectomy. METHODS: Thirty-six patients undergoing initial vitrectomy with phacoemulsification and aspiration (PEA) were enrolled, and were divided randomly into three groups. Group 1 was treated with topical application of levofloxacin (three times on the day before surgery and seven times on the day of surgery), Group 2 received oral administration of levofloxacin (200 mg twice on the day before surgery and 200 mg at 3 hours before surgery), and Group 3 received both topical and oral levofloxacin according to the above schedules. The concentration of levofloxacin was measured in aqueous humor and vitreous fluid samples obtained during surgery. RESULTS: In Groups 1, 2, and 3, the mean levofloxacin concentration in aqueous humor was 0.765+/-0.624 micro g/mL, 1.279+/-0.440 micro g/mL, and 1.823+/-0.490 micro g/mL, respectively, while the mean levofloxacin concentration in vitreous fluid was <0.02 micro g/mL, 1.455+/-0.445 micro g/mL, and 1.369+/-0.530 micro g/mL, respectively. CONCLUSIONS: Oral administration of levofloxacin at a dose of 400 mg/day was sufficient for the prophylaxis of ocular infections, because the drug concentrations in both aqueous humor and vitreous fluid were higher than the MIC90 values for major ocular pathogens. Topical application of levofloxacin achieved adequate drug levels in aqueous humor, but not in vitreous fluid, while combined topical and oral administration had an additive effect on the drug concentration in aqueous humor.     

Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration

OBJECTIVE: To evaluate the penetration of commercially available levofloxacin 0.5%, ofloxacin 0.3%, and ciprofloxacin 0.3% topical ophthalmic solutions in human corneal stromal and aqueous humor tissues. METHODS: A total of 67 patients scheduled to undergo penetrating keratoplasty for treatment of stromal scar or dystrophy, keratoconus, pellucid marginal degeneration, or endothelial disease were enrolled in this prospective, double-blind, 3-center study. To be considered for inclusion, patients had to have an intact corneal epithelium and minimal or no corneal edema (pachymetry < 650 microm). After informed consent was obtained, patients were randomized to receive 1 drop of levofloxacin 0.5%, ofloxacin 0.3%, or ciprofloxacin 0.3% topical ophthalmic solution at approximately 15 and 10 minutes before surgery. Approximately 0.1 mL of aqueous fluid was aspirated by paracentesis through the trephination wound at the onset of surgery, followed by excision of the affected cornea and removal of its epithelium. Specimens were stored frozen at -70 degrees C until assayed by high-performance liquid chromatography. RESULTS: All 3 fluoroquinolones were well tolerated. A total of 65 corneas and 59 aqueous fluid samples were obtained and assayed. The mean +/- standard deviation corneal concentrations of ciprofloxacin, ofloxacin, and levofloxacin following a 2-drop administration were 9.92 +/- 10.99 microg/g (n = 18), 10.77 +/- 5.90 microg/g (n = 23), and 18.23 +/- 20.51 microg/g (n = 24), respectively. Although corneal stromal levels were highest in the levofloxacin group, the high degree of interpatient variability prevented demonstration of statistically significant differences when compared with ofloxacin (P = 0.377). In contrast, levofloxacin concentrations were approximately twice as high as ciprofloxacin, and this difference reached statistical significance (P = 0.014). The corresponding aqueous humor concentrations of ciprofloxacin, ofloxacin, and levofloxacin were 0.135 +/- 0.231 microg/mL (n = 15), 0.135 +/- 0.111 microg/mL (n = 20), and 0.372 +/- 0.546 microg/mL (n = 24, P < 0.001 versus ciprofloxacin and ofloxacin). CONCLUSION: The topical administration of all 3 agents was well tolerated in patients undergoing penetrating keratoplasty. Two drops of levofloxacin 0.5% solution results in a 1.7- to 2.7-fold greater penetration into human corneal stromal and aqueous humor tissues than ofloxacin 0.3% or ciprofloxacin 0.3%. The mean intracorneal concentrations of all three agents following 2 drops exceeds the MIC90 for the majority of pathogens causing bacterial keratitis. Topical levofloxacin appears to offer pharmacokinetic and pharmacodynamic advantages over ofloxacin and ciprofloxacin in terms of enhanced transcorneal penetration; however, clinical comparative trials are needed to confirm these relative advantages.     

Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given in different concentrations in a wick before cataract surgery

PURPOSE: To determine whether the penetration into the aqueous humor of gatifloxacin (Zymar) and moxifloxacin (Vigamox) eyedrops was affected by altering their concentrations in the dilating mixture in which the wick used to dilate the pupil before cataract surgery was soaked. SETTING: Pasqua Hospital, Regina, Saskatchewan, Canada. METHODS: This prospective randomized open-label study comprised 65 women and 35 men who were divided into 2 main groups. One group received 1 mL of the antibiotic in the dilating mixture and the other, 2 mL. Each group was divided into 2 subgroups, 1 for gatifloxacin and 1 for moxifloxacin. At the beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and couriered to the provincial laboratory for analysis by high-performance liquid chromatography. RESULTS: In the first group, the mean concentration of gatifloxacin in the aqueous humor was 0.30 microg/mL +/- 0.21 (SD) and of moxifloxacin, 0.97 +/- 0.63 microg/mL. When the volume of the antibiotic in the dilating mixture was doubled, the mean concentration increased to 0.34 +/- 0.25 microg/mL and 1.37 +/- 0.79 microg/mL, respectively. Only the increased penetration of moxifloxacin was statistically significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than gatifloxacin when given in a wick soaked in the dilating mixture before cataract surgery. Only the penetration of moxifloxacin increased significantly when the volume of the antibiotic in the dilating mixture was doubled. In both groups, only moxifloxacin reached and exceeded the minimum inhibitory concentration levels for the most common ocular pathogens causing endophthalmitis.     

Aqueous and vitreous penetration of levofloxacin after oral administration

OBJECTIVE: To investigate the penetration of levofloxacin, an optical S-(-)isomer of ofloxacin, into the aqueous and vitreous humor after oral administration. DESIGN: Randomized, clinical trial comparing tissue levels of levofloxacin after one or two doses 12 hours apart. PARTICIPANTS: Forty-five patients undergoing initial vitrectomy between February 1997 and June 1997 at the UIC Eye Center. METHODS: Aqueous, vitreous, and serum samples were obtained and later analyzed from 45 patients after oral administration of 1 500-mg tablet (group 1, 22 patients) or 2 500-mg tablets (group 2, 23 patients) 12 hours apart before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and serum concentrations of levofloxacin (micrograms/milliliter). RESULTS: Group 1 achieved mean aqueous, vitreous, and serum levels of 0.59 +/- 0.48 microg/ml, 0.32 +/- 0.34 microg/ml, and 4.34 +/- 3.59 microg/ml, respectively. Group 2 achieved mean aqueous, vitreous, and serum levels of 1.90 +/- 0.97 microg/ml, 2.39 +/- 0.70 microg/ml, and 8.02 +/- 3.14 microg/ml. CONCLUSIONS: Mean inhibitory aqueous and vitreous MIC90 levels were achieved against a majority of ocular pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae (vitreous), Bacillus cereus (vitreous), Haemophilus influenzae, Moraxella catarrhalis, and most gram-negative aerobic organisms except Pseudomonas aeruginosa after two doses given 12 hours apart. Mean MIC90 levels were obtained in the vitreous for a majority of pathogens responsible for traumatic, postoperative, or bleb-related endophthalmitis.     

Vitreous and aqueous penetration of orally administered moxifloxacin in humans

OBJECTIVE: To investigate the intraocular penetration of moxifloxacin into the aqueous and vitreous after oral administration in humans. METHODS: A prospective, nonrandomized study of 27 consecutive patients scheduled for elective parsplana vitrectomy surgery between 1 October and 31 December 2004 was carried out. Aqueous, vitreous, and serum samples were obtained and analysed after oral administration of a single 400 mg tablet of moxifloxacin a few hours before surgery. Assays were performed using high-performance liquid chromatography. RESULTS: Mean+/-SD moxifloxacin concentrations in the serum (n=27), aqueous (n=25), and vitreous (n=27) were 1.34+/-0.98, 0.21+/-0.21, and 0.09+/-0.09 microg/ml, respectively. The mean+/-SD sampling times after oral administration of the moxifloxacin tablet for serum, aqueous, and vitreous were 2.02+/-0.51, 1.53+/-0.45, and 1.55+/-0.46 h, respectively. The minimum inhibitory concentration for 90% of isolates (MIC90) was far exceeded in the aqueous for a wide spectrum of key pathogens, whereas it was not exceeded in the vitreous for several organisms. Of note, the MIC90 for Staphylococcus epidermidis was not exceeded in any of the samples. CONCLUSIONS: Orally administered moxifloxacin achieves measurable levels in the noninflammed human eye, with the aqueous levels effective against a variety of pathogens. However, the spectrum of coverage does not appropriately encompass the most common causative organisms in endophthalmitis, especially Staphylococcus epidermidis. Further studies are needed to precisely define the role of oral moxifloxacin in the treatment of or prophylaxis against intraocular infections.     

Penetration of topical and oral ciprofloxacin into the aqueous and vitreous humor in inflamed eyes.

PURPOSE: To assess the aqueous and vitreous penetration of ciprofloxacin after topical and combined topical and oral administration and investigate the effects of inflammation on drug penetration. METHODS: A standardized penetrating injury was made in the right eyes of 16 rabbits. Intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in these eyes. The animals were divided into two groups according to treatment methodology: topical and topical-oral. The intact left eyes of the animals were maintained as controls. In the topical treatment group, two drops of ciprofloxacin 0.3% were instilled to both eyes every 30 minutes for 4 hours. In the topical-oral treatment group, animals were given two oral 40 mg/kg doses of ciprofloxacin at 12-hour intervals. After the last oral dose, the protocol of the topical group was applied to these eyes. Half an hour after the last drop, 100-microL samples were taken from aqueous and vitreous humor of all eyes. Drug concentrations were measured using high-pressure liquid chromatography. RESULTS: Mean aqueous levels of ciprofloxacin in control eyes were 2.31 microg/mL (range, 1.02-6.27 microg/mL) in the topical group and 5.88 microg/mL (1.52-17.81) in the topical-oral group. Mean aqueous levels in inflamed eyes were 7.36 microg/mL (2.34-17.15) in the topical group and 14.43 microg/mL (2.18-18.66) in the topical-oral group. Mean vitreous levels in control eyes were 0.77 microg/mL (0.09-1.93) in the topical group and 1.01 microg/mL (0.49-1.57) in the topical-oral group. Mean vitreous levels in inflamed eyes were 0.95 microg/mL (0.18-1.27) in the topical group and 1.98 microg/mL (0.51-3.34) in the topical-oral group. There was no significant difference among the groups (P > 0.05). Mean aqueous levels in all eyes and mean vitreous levels in the combined topical and oral group of inflamed eyes were above the 90% minimum inhibitory concentration for most of the common microorganisms causing endophthalmitis. CONCLUSION: There is an increase in both aqueous and vitreous humor concentrations with inflammation and with oral and topical administrations, as opposed to topical only, of ciprofloxacin. Using oral as well as topical treatment may be a beneficial method of antibiotic prophylaxis in ocular trauma once a patient has received intravenous or intravitreal therapy.     

Aqueous humor levels of topically applied levofloxacin in human eyes

PURPOSE: To evaluate transcorneal penetration of topically applied 0.5% levofloxacin into the aqueous humor in human eyes. METHODS: Twenty cataract patients (14 females, 6 males) received 3 drops of 0.5% levofloxacin at 15 min intervals from 90 minutes before the surgery. At the beginning of the cataract surgery, 50 microL of aqueous humor was aspirated from the anterior chamber and stored at -80 degrees C until analysis. The drug concentration of the samples was analyzed using high-performance liquid chromatography. RESULTS: A mean aqueous humor level of levofloxacin was 1.00 +/- 0.48 microg/mL (mean +/- standard deviation, n = 20), ranging from 0.30 microg/mL to 2.32 microg/mL. CONCLUSIONS: The mean concentration of levofloxacin in the aqueous humor was higher than the MIC(90) values against some common pathogens of postoperative endophthalmitis, although a great degree of interpatient variability was present.     

Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration

OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively. CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.     

Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given by different methods before cataract surgery

PURPOSE: To determine whether the penetration into the aqueous humor of 2 new fourth-generation fluoroquinolone antibiotics, gatifloxacin (Zymar) and moxifloxacin (Vigamox) eyedrops, was affected by different methods of administration before cataract surgery. SETTING: Pasqua Hospital, Regina, Saskatchewan, Canada. METHODS: This prospective randomized study comprised 193 patients. The patients were divided into 2 main groups. One group received gatifloxacin eyedrops and the other, moxifloxacin eyedrops. Each group was subdivided into 4 subgroups. All patients received the drops 4 times a day starting 2 days preoperatively. The first subgroup did not receive any more antibiotics. The second subgroup received the antibiotic drops 3 times, starting approximately 2 hours preoperatively. The third subgroup received a wick soaked in a dilating mixture containing the antibiotic. The fourth subgroup received the wick and the antibiotic drops at the time of preparation for surgery. At the beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and sent under ice by courier to the Provincial Laboratory for analysis by high-performance liquid chromatography. RESULTS: The study included 124 women and 69 men. The mean concentrations in the aqueous humor were 0.19, 0.82, 0.22, and 0.30 microg/mL in the 4 gatifloxacin subgroups, respectively, and 0.38, 2.16, 0.88, and 0.97 microg/mL in the 4 moxifloxacin subgroups, respectively. Analysis of variance showed the differences between the 2 antibiotics to be statistically significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than gatifloxacin regardless of the method of administration. Both antibiotics penetrated the aqueous humor well when given in drop form. They reached and exceeded the minimum inhibitory concentration levels for the most common ocular pathogens causing endophthalmitis. Only moxifloxacin reached these levels when the wick was used.     

Vitreous penetration of levofloxacin in the uninflamed phakic human eye

AIMS: To assess the vitreous penetration of oral levofloxacin (a new fluoroquinolone antibiotic with improved Gram positive activity) in uninflamed phakic eyes. METHODS: 15 patients for macula hole surgery were recruited to the study. 10 received a single 500 mg dose of levofloxacin by mouth preoperatively. Five acted as controls. Serum and undiluted vitreous samples were obtained at surgery and analysed by HPLC. RESULTS: Levofloxacin was detectable 2.5 hours after administration in the vitreous. A peak concentration of 1.6 microg/ml (or mg/l) was measured between 2.5 and 4 hours post-dose. CONCLUSION: Oral levofloxacin reaches the vitreous rapidly in the uninflamed phakic eye. Levels did not reach MIC(90) for the commonest infecting organisms. Nevertheless, levofloxacin would be expected to be active against a higher proportion of infecting organisms than either ciprofloxacin or ofloxacin.     

Penetration of second-, third-, and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model

AIMS: This study was designed to investigate the penetration of second-, third- and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model. METHODS: Thirty New Zealand white rabbits were divided into six groups. Left eye was infected with an intravitreal inoculum of Staphylococcus aureus. Groups 1, 2, 3, 4, and 5 received topical ofloxacin, ciprofloxacin, lomefloxacin, levofloxacin, or moxifloxacin treatment 24 h after the inoculation, respectively. No treatment was given to group 6 as the control group (n=5). Aqueous and vitreous samples were obtained 30 min after the last drop. High-performance liquid chromatography was used to determine the fluoroquinolone concentration. RESULTS: In the normal and inflamed eyes, mean aqueous concentrations of ofloxacin were 1.90 and 2.69 mug/ml, ciprofloxacin were 2.16 and 3.65 mug/ml, lomefloxacin were 3.54 and 1.19 mug/ml, levofloxacin were 2.89 and 9.41 mug/ml, and moxifloxacin were 4.92 and 43.33 mug/ml, respectively. Mean vitreous concentrations of ofloxacin were 0.25 and 0.07 mug/ml, ciprofloxacin were 0.08 and 0.32 mug/ml, lomefloxacin were 0.001 and 0.03 mug/ml, levofloxacin were 0.03 and 0.09 mug/ml, and moxifloxacin were 0.28 and 2.68 mug/ml, in normal and inflamed eyes, respectively. Moxifloxacin achieved a significantly higher concentration in aqueous and vitreous humour of infected eyes compared with ofloxacin (P<0.01), ciprofloxacin (P<0.05), lomefloxacin (P<0.01), and levofloxacin (P<0.05). CONCLUSION: This study demonstrated that fourth-generation fluoroquinolone, moxifloxacin, seems to have better penetration to inflamed ocular tissues in rabbit.     

Differential aqueous and vitreous concentrations of moxifloxacin and ofloxacin after topical administration one hour before vitrectomy

PURPOSE: To investigate the penetration of ofloxacin and moxifloxacin into the aqueous and vitreous after topical administration one hour before vitrectomy surgery. DESIGN: Prospective, randomized, double-blind case series study. METHODS: Twenty-seven patients undergoing vitrectomy were randomized to receive either topical ofloxacin 0.3% or moxifloxacin 0.5% every 10 minutes for one hour before surgery. Aqueous and vitreous samples were obtained and analyzed using high-performance liquidation chromatography. RESULTS: The moxifloxacin aqueous (1.576 +/- 0.745 microg/ml) and vitreous (0.225 +/- 0.013 microg/ml) levels were significantly higher than the ofloxacin aqueous (0.816 +/- 0.504 microg/ml) (P = .0009) and vitreous (0.225 +/- 0.013 microg/ml) [P = .0054] levels, respectively. The mean moxifloxacin aqueous and vitreous levels exceeded the minimum inhibitory concentration for 90% of isolates (MIC(90)) for a wide variety of bacteria implicated in endophthalmitis. In contrast, the aqueous level of ofloxacin exceeded the MIC(90) of only a few organisms. CONCLUSIONS: Moxifloxacin applied every 10 minutes during the hour before vitrectomy penetrated the eye significantly better than ofloxacin.     

Penetration of moxifloxacin into the human aqueous humour after oral administration

AIMS: To determine the pharmacokinetics of moxifloxacin, a new generation fluoroquinolone, in the anterior chamber of the human uninflamed eye. METHODS: 35 patients undergoing cataract surgery received two doses of 400 mg of oral moxifloxacin with a 12 hour interval and were divided into six groups. Moxifloxacin levels in aqueous humour and serum were determined by a microbiological agar well diffusion technique at 2, 4, 6, 8, 10, and 12 hours after the second dose in each group respectively. RESULTS: Mean moxifloxacin levels in the anterior chamber were 1.20 (SD 0.35) microg/ml at the 2 hours group, 1.22 (0.48) microg/ml at the 4 hours group, 1.20 (0.45) microg/ml at the 6 hours group, 1.58 (0.38) microg/ml at the 8 hours group, 1.37 (0.44) microg/ml at the 10 hours group, and 1.23 (0.55) microg/ml at the 12 hours group. The mean ratio of aqueous to serum moxifloxacin level was 38%. CONCLUSION: Moxifloxacin penetrates well into the anterior chamber of the human uninflamed eye after oral administration, reaching early significant levels, which are maintained for at least 12 hours and are much higher than the MIC(90) values of Gram positive and Gram negative pathogens commonly implicated in intraocular infections with the exceptions of fluoroquinolone resistant staphylococci, MRSA, and Pseudomonas aeruginosa.     

Vitreous penetration of topical moxifloxacin and gatifloxacin in humans

PURPOSE: To determine the vitreous penetration of the new fourth-generation topical fluoroquinolones moxifloxacin 0.5% and gatifloxacin 0.3%. METHODS: A prospective randomized clinical trial comprising 12 eyes of 12 patients scheduled for pars plana vitrectomy between August 2003 and September 2003 was performed in a clinical practice. The patients were randomly assigned to receive topical moxifloxacin 0.5% (n = 6) or gatifloxacin 0.3% (n = 6). One half the patients in each antibiotic group received 1 drop every 15 minutes for a total of 3 doses starting 1 hour before surgery, and the other one half self-administered the antibiotic drop 4 times daily for 3 days before surgery and at 7 am on the day of surgery. Undiluted vitreous samples were obtained and analyzed using high-performance liquid chromatography. RESULTS: Either moxifloxacin 0.5% or gatifloxacin 0.3% was detected in the vitreous in all 12 patients in the study. There was no significant difference between the mean vitreous concentration of moxifloxacin 0.5% given over 1 hour preoperatively (0.012 +/- 0.011 microg/mL) and that given in the 3-day regimen (0.011 +/- 0.008 microg/mL) (P = 0.93). There was also no significant difference between the mean vitreous concentration of gatifloxacin 0.3% given over 1 hour preoperatively (0.001 +/- 0.0003 microg/mL) and that given over 3 days (0.008 +/- 0.006 microg/mL) (P = 0.11). Vitreous concentrations of moxifloxacin 0.5% and gatifloxacin 0.3% in each eye were all lower than the 90% minimum inhibitory concentration for the commonest bacterial isolates causing endophthalmitis. With both dosing regimens, the mean vitreous concentration of moxifloxacin 0.5% was higher than that of gatifloxacin 0.3% administered at the same regimen, but this was not statistically significant. CONCLUSION: Both topical moxifloxacin 0.5% and gatifloxacin 0.3% penetrated the vitreous in the uninflamed eye, but the vitreous concentrations attained were all lower than the 90% minimum inhibitory concentration for the commonest bacterial pathogens causing acute postoperative endophthalmitis.     

Intraocular concentrations of gatifloxacin and moxifloxacin in the anterior chamber via diffusion through the cornea using collagen shields

PURPOSE: To evaluate the penetration of gatifloxacin and moxifloxacin into the anterior chamber, and any adverse reaction to the cornea, using collagen shields presoaked in oversaturated solutions of the antibiotics. METHODS: Collagen shields, presoaked for 10 minutes in an oversaturated solution of gatifloxacin or moxifloxacin, were placed on the surface of each of the corneas of 15 rabbits for a total of 30 eyes (15 in each group). The antibiotics were prepared by dissolving the powder form of the antibiotics in a solution until no further particulate could be further dissolved. Aqueous humor samples were taken 3.5 and 6 hours later. RESULTS: The initial concentrations of gatifloxacin and moxifloxacin were 5.43 +/- 0.16 mg/mL and 3.14 +/- 0.22 mg/mL, respectively. The average concentration of gatifloxacin in the anterior chamber was higher than that of moxifloxacin at the 3.5-hour sample (6.32 +/- 2.67 microg/mL versus 3.55 +/- 3.5 microg/mL, P = 0.0034). The concentrations of both antibiotics, although decreased, remained relatively high at the 6-hour sample (1.39 +/- 1.13 microg/mL versus 0.816 +/- 0.6 microg/mL at 6 hours, respectively, P = 0.22). No obvious clinical or histologic signs of toxicity were noticed in either group. CONCLUSION: Gatifloxacin and moxifloxacin showed good penetration into the anterior chamber with no obvious adverse reaction to the cornea. The concentrations in the anterior chamber exceeded the minimal inhibitory concentration (MIC) 90 of most organisms responsible for postoperative endophthalmitis (POE).     

Aqueous humor levels of topically applied levofloxacin, norfloxacin, and lomefloxacin in the same human eyes

PURPOSE: To assess the relative penetration of topical eyedrops of 3 fluoroquinolones into the aqueous humor in human eyes. SETTING: Department of Ophthalmology, Sano-Kosei Hospital, Sano, Japan. METHODS: Fifty-nine cataract patients (36 women, 23 men) received 3 drops each of levofloxacin 0.5%, norfloxacin 0.3%, and lomefloxacin 0.3% in the same eye at 15-minute intervals beginning 90 minutes before cataract surgery. At the beginning of surgery, 50 microL of aqueous humor was aspirated from the anterior chamber and stored at -80 degrees C until analyzed. The drug concentrations in the samples were analyzed using high-performance liquid chromatography. RESULTS: Five patients were excluded from the study because their sample volumes were insufficient. Norfloxacin was detected in 3 patients; the mean aqueous humor level was 0.10 microg/mL +/- 0.02 (SD). Levofloxacin was detected in all cases; the mean aqueous humor level was 0.60 +/- 0.28 microg/mL (n = 54). Lomefloxacin was not detected in 10 patients; the mean aqueous humor level was 0.23 +/- 0.11 microg/mL (n = 44). CONCLUSION: Topically applied levofloxacin had better penetration into the aqueous humor than lomefloxacin and norfloxacin.     

Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous

PURPOSE: To determine the intraocular penetration of topical drops of 2 antibiotics, ciprofloxacin 0.3% and ofloxacin 0.3%, into the aqueous humor and vitreous and to relate these levels to the miminum inhibitory concentration (MIC(90)) for organisms associated with ocular bacterial infections. SETTING: Department of Ophthalmology, Ankara Hospital, and Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. METHODS: This prospective randomized clinical trial comprised 18 patients having cataract surgery, all with an intact corneal epithelium. The patients were randomly assigned to receive topical ciprofloxacin 0.3% (n = 10) or topical ofloxacin 0.3% (n = 8) 1 drop every 15 minutes 5 times and every 30 minutes 3 times before surgery. Aqueous and vitreous samples (if vitreous loss occurred during the cataract surgery) were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography (HPLC) fluorescence. RESULTS: All patients had detectable drug concentrations in the aqueous humor and vitreous measurable by HPLC. The mean aqueous humor concentration of ciprofloxacin was 1.13 microg/mL +/- 1.90 (SD) and the mean vitreous concentration, 0.23 +/- 0.06 microg/mL. Topical administration of ciprofloxacin yielded 4.9 times more drug concentration in the anterior chamber than in the vitreous. The mean aqueous concentration of ofloxacin was 2.06 +/- 1.06 microg/mL and the mean vitreous concentration, 0.46 +/- 0.10 microg/mL. Topical administration of ofloxacin yielded 4.7 times more drug concentration in the anterior chamber than in the vitreous. Aqueous humor concentrations of ofloxacin and ciprofloxacin were not statistically significantly different (P =.353). Intravitreal concentrations of ofloxacin were statistically significantly higher than those of ciprofloxacin (P =.001). CONCLUSIONS: Topical ofloxacin 0.3% penetrated better than topical ciprofloxacin 0.3% into the anterior chamber and vitreous in noninflamed eyes. Both drugs were above the MIC(90) for most ocular pathogens in the anterior chamber. The mean concentration in the vitreous of topically applied ofloxacin 0.3% was statistically significantly higher than that of ciprofloxacin 0.3%, but it was not sufficiently above the MIC(90) for most ocular pathogens in terms of empirical endopthalmitis therapy.