Phase 3 safety comparisons for 1.0% azithromycin in polymeric mucoadhesive eye drops versus 0.3% tobramycin eye drops for bacterial conjunctivitis

PURPOSE: To compare the safety and tolerability of 1.0% azithromycin in a polymeric mucoadhesive delivery system with 0.3% tobramycin ophthalmic solution for the treatment of bacterial conjunctivitis. METHODS: This study was a prospective, randomized, active-controlled, double-masked, phase 3 trial conducted from August 6, 2004, to October 6, 2005, at 47 sites. Subjects with a clinical diagnosis of bacterial conjunctivitis were randomly assigned to receive either 1% azithromycin in DuraSite (AzaSite; InSite Vision, Alameda, CA) (n = 365) or 0.3% tobramycin (n = 378). Both groups received masked medication four times daily for 5 days, but participants received an active dose of 1% azithromycin in DuraSite only twice a day on days 1 and 2 and daily on days 3 to 5. Conjunctival cultures were taken, and ocular signs and symptoms were evaluated at baseline and at two follow-up visits. RESULTS: A total of 743 patients were randomized, and 710 (96%) completed the trial. Both study medications were well tolerated. The most frequently observed ocular adverse events in the azithromycin group were eye irritation (1.9%), conjunctival hyperemia (1.1%), and worsening bacterial conjunctivitis (1.1%). These rates compared favorably with those obtained with tobramycin. Rates of microbial eradication (an efficacy parameter) and bacterial infection recurrence (a safety parameter) were the same in both groups. CONCLUSIONS: This is the first report of the safety and tolerability of a commercially manufactured preparation of azithromycin for ophthalmic use. Azithromycin 1% in DuraSite is safe and can be administered in a regimen of less frequent doses than can tobramycin, while producing an equivalent clinical outcome. The formulation is well tolerated in patients over the age of 1 year for the eradication of bacteria commonly associated with conjunctivitis. (ClinicalTrials.gov number, NCT00105469.).     

Clinical efficacy of ciprofloxacin 0.3%9 (Ciloxan) in the treatment of bacterial infections of the external eye segment

PURPOSE: The main subject of the study was to evaluate efficacy of ciprofloxacin 0.3% ophthalmic solution (Ciloxan) in the treatment of bacterial conjunctivitis and surgical prophylaxis. Safety and comfort of topical ciprofloxacin treatment was also examined. MATERIAL AND METHODS: Two study arms: 99 patients with bacterial conjunctivitis (A group) and 48 patients awaiting cataract surgery (B group--total 147 subjects in both groups) received ciprofloxacin 0.3% ophthalmic solution (Ciloxan) 4 doses a day for seven days. Bacteriological evaluation was established before and after treatment for each eye. RESULTS: 95 out of the 99 patients (96%) in the first arm were completely cured (all signs and symptoms of the bacterial conjunctivitis were eliminated). In the second arm complete eradication of bacterial flora was achieved in 46 out of 48 pretreated patients (96%). CONCLUSIONS: Topical ciprofloxacin 0.3% (iloxan) was found very effective and fast in reduction of typical signs and symptoms of bacterial conjunctivitis as well as in eradication of bacterial flora before surgery treatment.     

Clinical cure of bacterial conjunctivitis with azithromycin 1%: vehicle-controlled, double-masked clinical trial

PURPOSE: To analyze the effect of azithromycin 1% ophthalmic solution in DuraSite (InSite Vision, Inc, Alameda, California, USA) on bacterial conjunctivitis. DESIGN: Prospective, randomized, vehicle-controlled, parallel-group, double-masked multicenter clinical study. METHODS: Eligible male or female participants with a clinical diagnosis of acute bacterial conjunctivitis were randomized to either 1% azithromycin in DuraSite or vehicle for five days. Infected eyes were dosed twice daily on days 1 and 2 and once daily on days 3 through 5. Conjunctival cultures were obtained at baseline, visit 2 (day 3 or 4), and visit 3 (day 6 or 7). The primary end point was clinical resolution of signs and symptoms (rating of zero on ocular discharge, bulbar and palpebral injection) at visit 3. Efficacy measures were clinical resolution and bacterial eradication as evaluated in the per-protocol population. Safety was assessed by adverse events, slit-lamp findings, and ophthalmoscopy. RESULTS: Two hundred and seventy-nine participants (n = 130, 1% azithromycin in DuraSite; n = 149, vehicle), age one to 96 years, were evaluated for efficacy. Clinical resolution with azithromycin ophthalmic solution was statistically significant compared with that of vehicle (P = .030) at visit 3. Bacterial eradication rates with azithromycin ophthalmic solution reached 88.5% at visit 3 (P < .001) and included some pathogens resistant to azithromycin in vitro. Overall, adverse event rates were similar in both treatment groups. CONCLUSIONS: Azithromycin 1% ophthalmic solution in DuraSite showed statistically significant differences in clinical resolution and bacterial eradication rates when compared with vehicle. Because it was well tolerated in this population, it may be a viable treatment option for children and adults with bacterial conjunctivitis.     

A phase III clinical trial of 0.5% levofloxacin ophthalmic solution versus 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis

OBJECTIVE: To compare the efficacy and safety of 0.5% levofloxacin ophthalmic solution (QUIXIN) with 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis. DESIGN: Prospective, randomized, active-controlled, double-masked, multicenter study. PARTICIPANTS: Four hundred twenty-three patients with a clinical diagnosis of bacterial conjunctivitis were enrolled. METHODS: Patients were randomly assigned to receive either 0.5% levofloxacin (n = 211) or 0.3% ofloxacin (n = 212) for 5 days (every 2 hours on days 1 and 2 and every 4 hours on days 3-5). Conjunctival cultures were obtained, and ocular signs and symptoms were evaluated on day 1 (baseline), days 3 to 5 (interim), and days 6 to 10 (final). End point was defined as the last evaluable observation. MAIN OUTCOME MEASURES: Primary microbial and clinical outcomes were based on culture results and resolution of cardinal signs, respectively. Secondary efficacy assessments included evaluations of ocular signs and symptoms. RESULTS: Two hundred eight patients (levofloxacin, n = 109; ofloxacin, n = 99) were evaluated for efficacy. Microbial eradication rates were 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 was 0.3% ofloxacin treatment (94% vs. 73%, P = 0.006). Both study medications were well tolerated, with a low incidence of adverse events. CONCLUSIONS: Although clinical cure rates in the 0.5% levofloxacin and 0.3% ofloxacin treatment groups were similar, a 5-day treatment regimen with 0.5% levofloxacin achieved microbial eradication rates that were statistically superior to those attained with 0.3% ofloxacin. Despite the higher concentration of active drug in 0.5% levofloxacin versus 0.3% ofloxacin, there was no difference between treatment groups in the incidence of treatment-related adverse events.     

A phase III,placebo controlled clinical trial of 0.5% levofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis

AIM: To compare the efficacy and safety of levofloxacin 0.5% ophthalmic solution (Quixin) with placebo for treatment of bacterial conjunctivitis. METHODS: In this prospective, randomised, placebo controlled, double masked, multicentre study, 249 patients with bacterial conjunctivitis received either 0.5% levofloxacin (n = 126) or placebo (n = 123) for 5 days, administered every 2 hours on days 1-2, then every 4 hours on days 3-5. Cultures were obtained and signs/symptoms evaluated at baseline, interim, and final visits. The end point was the last evaluable observation. Primary microbial outcomes were based on culture results; clinical outcomes were based on resolution of cardinal signs. RESULTS: 117 patients (60 levofloxacin, 57 placebo) were evaluated. Microbial eradication rates were significantly greater with levofloxacin at all time points, reaching 90% at end point. In a subgroup analysis, differences in eradication rates at end point were most pronounced in children but were also statistically significant for levofloxacin in adults. Clinical cure rates were significantly greater with levofloxacin at final visit and end point. Statistically significant differences favouring levofloxacin were measured at end point for resolution of conjunctival discharge, bulbar conjunctival injection, palpebral conjunctival injection, burning/stinging, itching, and photophobia. Adverse events were similar between groups. Safety composite scores analysed by age indicated significantly fewer children on levofloxacin experienced worsening symptoms. CONCLUSIONS: Levofloxacin 0.5% ophthalmic solution is safe and effective for treatment of bacterial conjunctivitis.     

Efficacy and safety of 0.5% levofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis in pediatric patients.

PURPOSE: To compare the efficacy and safety of 0.5% levofloxacin ophthalmic solution (Quixin; Santen, Napa, CA) with 0.3% ofloxacin (Ocuflox; Allergan Inc., Irvine, CA) and placebo for the treatment of pediatric bacterial conjunctivitis. METHODS: This study was a subset analysis of 167 pediatric patients (age range, 1 to 16 years) from two randomized, double-masked, multicenter, parallel group studies. Eye drops were instilled every 2 hours on days 1 and 2 and every 4 hours on days 3 through 5. Ocular signs and symptoms were noted, and conjunctival cultures were obtained on day 1 (baseline), days 3 to 5 (interim), and days 6 to 10 (final). Endpoint was defined as the last evaluable observation. Microbial and clinical outcomes were based on culture results and cardinal signs, respectively. RESULTS: At endpoint (mean of 6.5 days for 118 evaluable patients), 0.5% levofloxacin treatment demonstrated greater microbial eradication rates (percentage of patients with absence of causative organisms cultured at baseline) compared with 0.3% ofloxacin or placebo. In children age 2 to 11 years, this finding was statistically significant in favor of 0.5% levofloxacin (87% vs 62% with 0.3% ofloxacin [P < or =.032] and 88% vs 24% with placebo [P <.001]). No significant differences between treatment groups in microbial eradication rates were noted in other age subgroups. CONCLUSIONS: After 5 days of therapy, 0.5% levofloxacin ophthalmic solution was found to be safe and effective in treating pediatric bacterial conjunctivitis. Treatment with 0.5% levofloxacin achieved microbial eradication rates in children that were statistically superior to those attained with 0.3% ofloxacin or placebo.     

An efficacy and tolerance comparison of emedastine difumarate 0.05% and levocabastine hydrochloride 0.05%: reducing chemosis and eyelid swelling in subjects with seasonal allergic conjunctivitis. Emadine Study Group

PURPOSE: To compare emedastine ophthalmic solution 0.05% BID to levocabastine ophthalmic suspension 0.05% BID in reducing chemosis, eyelid swelling and other signs and symptoms in subjects with seasonal allergic conjunctivitis. METHODS: In a randomized, double-masked, parallel controlled study, emedastine ophthalmic solution 0.05% BID was compared to levocabastine ophthalmic suspension 0.05% BID for control of chemosis, eyelid swelling and other parameters in the environmental allergy study model. RESULTS: At Days 7, 14, 30 and 42, emedastine was significantly better than levocabastine at controlling chemosis and eyelid swelling (p < 0.05). A statistical trend was seen at Day 3 (0.05 < p < 0.10). Results were clinically relevant at Days 30 and 42. Emedastine was also significantly better at reducing redness and itching at Days 7, 14, 30 and 42 (p < 0.05). CONCLUSION: Emedastine is more efficacious than levocabastine in reducing chemosis, eyelid swelling and other efficacy variables associated with seasonal allergic conjunctivitis.     

Treatment of acute bacterial conjunctivitis: 1% fusidic acid viscous drops vs. 0.3% tobramycin drops

BACKGROUND: A frequent cause of conjunctivitis is an acute bacterial infection, presenting with mucopurulent discharge and conjunctival hyperemia. The authors compared the clinical and microbiologic efficacy, safety and acceptability of 1% fusidic acid viscous drops (Fucithalmic) with 0.3% tobramycin ophthalmic solution (Tobrex) in the treatment of suspected bacterial conjunctivitis. METHODS: Patients were recruited at 20 sites in Ontario, Saskatchewan and Alberta from October 1995 to December 1998. Patients who presented to their primary care physician with suspected bacterial conjunctivitis, as identified by conjunctival hyperemia and purulent or mucopurulent discharge, were eligible for the study. Patients were randomly assigned to receive 7 days of treatment with either 1% fusidic acid (one drop applied twice daily) or 0.3% tobramycin (one to two drops applied four to six times daily). The investigators were blinded as to treatment status. Bacteriologic samples were taken from the inferior conjunctival cul-de-sac on day 0 and at the end of treatment. Signs and symptoms of conjunctivitis were assessed at baseline and after 3 and 7 days of treatment. The acceptability of treatment was assessed by having the patient or the parent or guardian complete a questionnaire on degree of compliance and ease of use after 3 and 7 days of treatment. RESULTS: Conjunctival swabs were obtained from 484 patients (410 over 9 years of age and 74 aged 2 to 9 years) to determine baseline bacteriology. Of the 484, 319 (65.9%) (63% of the older patients and 80% of those aged 2 to 9 years) had positive results of culture for bacteria. Ninety-four patients (19%) (63 [15%] of the older patients and 31 [42%] of those aged 2 to 9 years) had per-protocol pathogens as defined by quantitative bacteriology criteria. There was a direct correlation between the presence of mucopurulent discharge and the presence of per-protocol pathogens. There were no significant differences in clinical or bacteriologic efficacy between the treatment groups. Treatment compliance was similar between the treatment groups for the older patients; however, for those aged 2 to 9 years, compliance was significantly better in the fusidic acid group than in the tobramycin group (85% vs. 47%) (p < 0.001). Significantly more patients in the fusidic acid group than in the tobramycin group rated treatment as convenient or very convenient, particularly among younger patients (97% vs. 54%) (p < 0.001). INTERPRETATION: The clinical and bacteriologic efficacy of fusidic acid viscous drops combined with the convenience of a twice-daily dosage regimen establishes this antibiotic as first-line treatment for suspected acute bacterial conjunctivitis and a favourable alternative to other broad-spectrum antibiotics.     

Topical lomefloxacin 0.3% twice daily versus tobramycin 0.3% in acute bacterial conjunctivitis: A multicenter double-blind phase III study.

AIMS/BACKGROUND: To evaluate in a double-masked comparative, prospective, randomized multicenter trial the efficacy of lomefloxacin 0.3% eye drops twice daily and of tobramycin eye drops 4 times daily in patients with acute bacterial conjunctivitis. METHODS: Ninety-nine subjects were enrolled: 50 were treated with lomefloxacin 0.3% eye drops twice daily and 49 with tobramycin 0.3% eye drops 4 times daily. In all patients, conjunctival swabbing and assessment of objective signs and of subjective symptoms were performed. RESULTS: There was no statistical difference for any individual sign or symptom or for the sum score of either key or other signs and symptoms at any of the examination days. The sum score of both key and other signs and symptoms decreased in both groups at day 3-4 as compared to baseline values (p < 0.0001). The decrease in both these scores continued significantly from day 3-4 to day 7-8 (p < 0.05) and was similar in the two treatment groups (p > 0.4). The lowest resistance rate was seen in lomefloxacin (3.5%) and in neomycin (7.0%), while tobramycin showed resistance in 10 out of 88 resistance strains (11.4%). CONCLUSION: Both lomefloxacin 0.3% twice daily and tobramycin 0.3% administered 4 times daily were well tolerated and showed a high degree of clinical and microbiological efficacy in the treatment of acute bacterial conjunctivitis. Lomefloxacin caused less resistance than other antibiotics evaluated.     

Efficacy of topical cyclosporin 0.05% in the treatment of posterior blepharitis.

We assessed the efficacy of topical cyclosporin 0.05% ophthalmic emulsion versus tobramycin 0.3%/dexamethasone 0.1% in patients with posterior blepharitis. Posterior blepharitis improved significantly from the initial study visit with both cyclosporin treatment and tobramycin/dexamethasone. Cyclosporin provided greater improvements in Schirmer's scores (P < 0.001) and tear break-up time (P = 0.018) than tobramycin/dexamethasone after 12 weeks of treatment. Eyelid health also improved in both groups, but the mean improvement in meibomian gland secretion quality was significantly greater with cyclosporin than with tobramycin/dexamethasone (P = 0.015). Moreover, a higher percentage of patients in the cyclosporin treatment group had improvements in symptoms of blurred vision, burning, and itching and more cyclosporin-treated patients experienced resolution of lid telangiectasia. The findings in this prospective study suggest that posterior blepharitis can be more effectively treated with cyclosporin than with tobramycin/dexamethasone. These findings should be further evaluated in large-scale, controlled, clinical trials.     

Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers

PURPOSE: To compare the steroid-induced intraocular pressure (IOP) and other ocular adverse effects of loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension with those of dexamethasone 0.1% and tobramycin 0.3% ophthalmic suspension. METHODS: Three hundred six healthy volunteers received either loteprednol etabonate/tobramycin (n = 156) or dexamethasone/tobramycin (n = 150) at 4-hour intervals 4 times a day in both eyes for 28 days in this randomized, double-masked, multicenter, parallel-group trial. IOP, visual acuity (VA), and ocular health were assessed at all study visits (days 1, 3, 8, 15, 22, and 29), whereas undilated direct ophthalmoscopy was completed at the baseline and final visits. Adverse events (AEs) were assessed at all follow-up visits. RESULTS: The number of subjects experiencing IOP increases of >or=10 mm Hg from baseline at any study visit for the loteprednol etabonate/tobramycin group (3 subjects, 1.95%) was significantly lower than that for the dexamethasone/tobramycin group (11 subjects, 7.48%; P = 0.0280), as were mean changes from baseline IOP (P < 0.05 at all visits). The lowest VA recorded for any subject at any visit was 20/40 and reductions of >or=2 lines at any visit were observed in 14 (4.55%) eyes for loteprednol etabonate/tobramycin and in 23 (7.82%) eyes for dexamethasone/tobramycin (P = 0.1257). Both treatments were well tolerated. CONCLUSIONS: Loteprednol/tobramycin was significantly less likely to produce elevations in IOP than was dexamethasone/tobramycin in healthy subjects treated for 28 days. Both loteprednol etabonate/tobramycin and dexamethasone/tobramycin were well tolerated with low risks for systemic AEs and ocular AEs other than elevation in IOP for dexamethasone/tobramycin.     

盐酸左氧氟沙星滴眼液治疗细菌性结膜炎及角膜炎随机双盲对照临床研究

目的　比较北京医工生物技术研究所研制的 15mg/5mL盐酸左氧氟沙星滴眼液和海伦滴眼液治疗细菌性结膜炎、角膜炎的疗效和安全性。方法　用随机、双盲、平行研究。共选择 60例患者分为试验组和对照组各 3 0例。疗程 3～ 14d ,主要疗效参数为治疗第 7、14d的临床疗效。结果　用药 7d细菌性结膜炎和角膜炎试验组总有效率为 72 %( 18/2 5 ) ;对照组总有效率为 84 62 % ( 2 2 /2 6)。用药 14d细菌性结膜炎和角膜炎试验组总有效率为 10 0 % ( 2 5 /2 5 ) ;对照组总有效率为 96 15 % ( 2 5 /2 6) ,两组间细菌性结膜炎和角膜炎总有效率无统计学差异。试验组和对照组对细菌性结膜炎和角膜炎的疗效相当。细菌性结膜炎和角膜炎试验组细菌清除率为 10 0 % ;对照组总清除率 98 0 4% ,两组间清除率比较无显著性差异 (P >0 0 5 )。试验组与对照组均有良好的耐受性 ,无明显不良反应发生。结论　盐酸左氧氟沙星滴眼液治疗细菌性结膜炎和细菌性角膜炎有效且安全。     

Penetration of topically administered ofloxacin and trimethoprim into aqueous humor.

Ocular penetration of two topical antibiotics used to treat bacterial conjunctivitis was assessed in adult volunteers scheduled for cataract surgery. In this randomized, parallel-group study, patients instilled trimethoprim sulfate 0.1%/polymyxin B (n = 23) or ofloxacin 0.3% (n = 25) QID for 3 days, plus 4 instillations in the hour before surgery. Analysis of aqueous humor samples obtained during surgery showed a 2.4-fold greater concentration of ofloxacin over trimethoprim (1.135 micro g/ml vs 0.470 micro g/ml; P <.0001). The greater concentration of ofloxacin in ocular tissue coupled with its superior antibacterial activity profile supports its use as an alternative to trimethoprim/polymyxin B for treatment of bacterial conjunctivitis.     

3-day treatment with azithromycin 1.5% eye drops versus 7-day treatment with tobramycin 0.3% for purulent bacterial conjunctivitis: multicentre, randomised and controlled trial in adults and children

AIM: To compare the efficacy and safety of Azyter, azithromycin 1.5% eye drops, for 3 days with tobramycin 0.3% for 7 days to treat purulent bacterial conjunctivitis. METHODS: This was a multicentre, randomised, investigator-masked study including 1043 children and adults with purulent bacterial conjunctivitis. Patients received either azithromycin 1.5% twice-daily for 3 days or tobramycin 0.3%, 1 drop every two hours for 2 days, then four times daily for 5 days. Clinical signs were evaluated and cultures obtained at D0, D3 and D9 (where D refers to "day"). Primary variable was the clinical cure at the Test-of-Cure (TOC)-visit (D9+/-1), for patients with D0-positive cultures. The cure was defined as: bulbar conjunctival injection and discharge scores of 0. RESULTS: Among 471 patients with D0-positivity in the per protocol set, 87.8% of the azithromycin 1.5% group and 89.4% of the tobramycin group were clinically cured at the TOC-visit. Azithromycin was non-inferior to tobramycin for clinical and bacteriological cure. Clinical cure was significantly higher with azithromycin 1.5% at D3. The safety profile of azithromycin was satisfactory with a good patient and investigator's acceptability. CONCLUSIONS: Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children.     

Safety and efficacy comparison of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects with allergic conjunctivitis. Emadine Study Group

PURPOSE: To determine the efficacy and tolerance of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects. METHODS AND MATERIALS: In a randomized, double-masked, parallel controlled study, emedastine 0.05% ophthalmic solution BID was compared to levocabastine 0.05% ophthalmic suspension BID, for control of the signs and symptoms of allergic conjunctivitis in pediatric subjects ages 3-16. Subjects who met all inclusion and exclusion criteria received masked study medication with instructions to instill drops twice daily, in the morning and evening. A diary was completed by the parents four times daily for the first two and last two weeks of the study. Treatment lasted 42 days. Drug efficacy was assessed at the initial administration in the office at Day 0 and after 3, 7, 14, 30 and 42 days. RESULTS: Overall results showed both drugs have an effect and that emedastine was significantly superior (p < 0.05) to levocabastine for the relief of chemosis on Days 14, 30 and 42; of itching on follow-up Days 30 and 42 (p < 0.05); of redness on Days 30 and 42; for eyelid swelling on Days 14 and 30; and for physician's impression score on Days 7, 14, 30 and 42. CONCLUSION: These results confirm previous preclinical and clinical data on the potent and long acting efficacy of this promising new ophthalmic anti-allergic drug, emedastine in pediatric subjects.     

Zymar (Gatifloxacin 0.3%) shows excellent Gram-negative activity against Serratia marcescens and Pseudomonas aeruginosa in a New Zealand White rabbit keratitis model

PURPOSE: Whereas gatifloxacin, a newer fluoroquinolone, was engineered to increase its Gram-positive potency, we assessed whether it still retained significant Gram-negative activity in vivo. Specifically, we compared the efficacy of Zymar (gatifloxacin 0.3%), Ciloxan (ciprofloxacin 0.3%), and fortified tobramycin (14 mg/mL) in the treatment of experimental Gram-negative bacterial infections of Serratia marcescens (SM) and Pseudomonas aeruginosa (PA) in the New Zealand White (NZW) rabbit keratitis model. METHODS: A total of 30 NZW rabbits each were intrastromally inoculated in both eyes with approximately 1000 CFU of SM and PA. By E-test, the minimum inhibitory concentrations (MICs; microg/mL) for SM were gatifloxacin (0.125), ciprofloxacin (0.047), and tobramycin (1.5), and for PA were gatifloxacin (0.125), ciprofloxacin (0.19), and tobramycin (0.5). After 16 hours, the rabbits were divided into 4 treatment groups: (1) Zymar, (2) Ciloxan, (3) fortified tobramycin, and (4) saline control. One drop was instilled in both eyes every 15 minutes for 5 doses and then every 30 minutes for 14 doses. One hour after the final treatment, the animals were euthanized, and bacterial colony counts from the corneas were determined. RESULTS: For SM, Zymar and Ciloxan significantly reduced (P < 0.001, ANOVA) the colony counts compared with tobramycin and saline control. Zymar was more effective than Ciloxan (P < 0.001, ANOVA). For PA, all antibiotics reduced equivalently the colony counts compared with the saline control (P = 0.005, ANOVA). CONCLUSIONS: The enhanced Gram-positive activity of gatifloxacin is not associated with any decreased Gram-negative activity in vivo. Zymar may prove useful for SM and PA keratitis.     

A controlled trial of povidone-iodine to treat infectious conjunctivitis in children

PURPOSE: To report the efficacy of povidone-iodine as a treatment for conjunctivitis in pediatric patients. DESIGN: Double-masked, controlled, prospective clinical trial. METHODS: In an ophthalmology clinic in a general hospital in Manila, Philippines, 459 children (mean [SD] age 6.6 [6.6] years; range, 7 months-21 years) with acute conjunctivitis were studied. Infected eyes were cultured for bacteria and underwent immunofluorescent testing for Chlamydia trachomatis. Viral conjunctivitis was diagnosed if bacterial cultures were negative and diagnostic criteria were met. Subjects were alternated to receive povidone-iodine 1.25% or neomycin-polymyxin-B-gramicidin ophthalmic solution, one drop 4 times daily in the affected eye. Ocular inflammation was evaluated daily by the family or patient and weekly by an ophthalmologist. The main outcome measures were days until cured and proportion cured after 1 and 2 weeks of treatment. RESULTS: Despite adequate statistical power (power >80% for a 1-day difference and P <.05), there was no significant difference between treatment groups regarding the number of days to cure or proportion cured at 1 or 2 weeks whether caused by bacteria or virus (P =.133-.824 for the four comparisons). After 1 week of treatment, povidone-iodine cured marginally more chlamydial infections than the antibiotic (P =.057). By 2 weeks, fewer chlamydial infections were cured than those of viral or bacterial etiology (P =.0001). The younger the patient, the faster their conjunctivitis resolved (R = 0.13, P =.013). CONCLUSIONS: Povidone-iodine 1.25% ophthalmic solution was as effective as neomycin-polymyxin B-gramicidin for treating bacterial conjunctivitis, somewhat more effective against chlamydia, and as ineffective against viral conjunctivitis. Povidone-iodine ophthalmic solution should be strongly considered as treatment for bacterial and chlamydial conjunctivitis, especially in developing countries where topical antibiotics are often unavailable or costly.     

Topically administered norfloxacin compared with topically administered gentamicin for the treatment of external ocular bacterial infections. The Worldwide Norfloxacin Ophthalmic Study Group.

In this double-masked study, we randomly assigned 488 patients with clinical signs of acute bacterial conjunctivitis or blepharitis, or both, to treatment with either norfloxacin ophthalmic solution 0.3% (245) or gentamicin ophthalmic solution 0.3% (243) for one week. Of the patients with positive cultures, 71% (85 of 120) of the norfloxacin-treated patients and 65% (86 of 133) of the gentamicin-treated patients were clinically cured. An additional 25% (30 of 120) of norfloxacin-treated patients and 32% (43 of 133) of gentamicin-treated patients were clinically improved. On the basis of posttreatment cultures, 89% of all cultured bacteria were eradicated (146 of 179 organisms) or suppressed (14 of 179 organisms) after treatment with norfloxacin. The condition of five norfloxacin-treated patients did not clinically improve, compared with the condition of eight gentamicin-treated patients. Both antibiotics had similar efficacy against gram-positive and against gram-negative organisms. One norfloxacin-treated patient and two gentamicin-treated patients withdrew from the study because of local intolerance. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the eyelids or conjunctiva, or both. In this study, norfloxacin was clinically and microbiologically similar in activity to gentamicin.     

Efficacy and safety of ketotifen eye drops in the treatment of seasonal allergic conjunctivitis

BACKGROUND: Ketotifen blocks histamine H(1) receptors, stabilises mast cells, and prevents eosinophil accumulation. These multiple, pharmacological mechanisms provided the rationale for assessing the efficacy and safety of ketotifen 0.025% eye drops in subjects with seasonal allergic conjunctivitis (SAC) in an environmental setting. METHODS: This was a double masked, randomised, multicentre trial conducted in Australia. Subjects were randomly assigned to ketotifen fumarate 0.025% ophthalmic solution, placebo (as vehicle), or levocabastine hydrochloride 0.05% ophthalmic suspension, twice daily in each eye for a 4 week period. Subjects were assessed at follow up (days 5-8) and termination (days 25-31) visits. The primary efficacy variable was the responder rate, based on the subjects' assessment of global efficacy at the follow up visit. RESULTS: 519 subjects were randomised to treatment. At the follow up visit, the responder rate, based on subjects' assessment of global efficacy, was significantly greater in the ketotifen group (49.5%) than in the placebo group (33.0%) for subjects with a positive diagnostic test for pollen allergy (p = 0.02). The investigators' assessment of responder rates also showed that ketotifen was superior to placebo (p = 0.001). Ketotifen produced a significantly better outcome than levocabastine (p<0.05) for relief of signs and symptoms of SAC, at both the follow up and the termination visit. The type and frequency of adverse events were similar across treatment groups. CONCLUSIONS: In an environmental setting, ketotifen fumarate 0.025% ophthalmic solution was well tolerated and effective in reducing the signs and symptoms of SAC, and in preventing their recurrence. Ketotifen consistently showed the best efficacy in comparison with both placebo and levocabastine. These results indicate that ketotifen eye drops are a valuable treatment option for this condition.     

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.