Topical 0.3% ciprofloxacin vs topical 0.3% ofloxacin in early treatment of Pseudomonas aeruginosa keratitis in a rabbit model

An in vivo prospective study compared the effectiveness of 0.3% ciprofloxacin to 0.3% ofloxacin against Pseudomonas aeruginosa keratitis in rabbits. Ofloxacin-treated corneas yielded an average amount of colony-forming units (CFUs) of P aeruginosa that was statistically significantly higher than that of ciprofloxacin-treated corneas (4.7×10⁴±2.2×10³ vs 2.5×10³±1.0×10²). Thus, ciprofloxacin was more effective than ofloxacin in the early reduction of CFUs in P aeruginosa keratitis in rabbits.     

Comparison of ophthalmic gatifloxacin 0.3% and ciprofloxacin 0.3% in healing of corneal ulcers associated with Pseudomonas aeruginosa-induced ulcerative keratitis in rabbits.

OBJECTIVE: Evaluation of gatifloxacin 0.3% ophthalmic solution efficacy in a corneal ulcer model of Pseudomonas keratitis. METHODS: Heptanol-induced corneal ulcers in New Zealand White rabbits (n = 41; 8 females/group) were inoculated with 10(6) CFU of Pseudomonas aeruginosa. Gatifloxacin 0.3% dosing varied among 4 groups with frequencies of 16-48 doses/day (days 1-2), 3-16 doses/day (days 3-7), and maintenance dosing of 3-4 doses/day (days 8-22). Ciprofloxacin 0.3% was administered as labeled for corneal ulcers, with 44 doses on day 1, 16 doses on day 2, and 4 doses/day on days 3-21. RESULTS: All eyes showed evidence of infection by 48 hours postinoculation with 36 of 41 eyes (87.8%) exhibiting moderate-to-severe keratitis. All eyes exhibited corneal healing by day 15, with no significant differences among groups. Three of 4 groups receiving gatifloxacin tended to have smaller fluorescein retention area scores than did the ciprofloxacin group. No eyes tested positive for Pseudomonas at the end of the study. No corneal precipitates were found following as many as 48 doses/day of gatifloxacin. CONCLUSION: Ophthalmic gatifloxacin 0.3% is at least as effective as ciprofloxacin at healing corneal ulcers infected with Pseudomonas aeruginosa when gatifloxacin is administered less frequently than ciprofloxacin. Trends favored gatifloxacin in fluorescein retention scores.     

Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment of patients with culture-positive bacterial keratitis

PURPOSE: To compare the efficacy and safety of ofloxacin 0.3% ophthalmic solution with ciprofloxacin 0.3% ophthalmic solution in patients with culture-positive bacterial keratitis. METHODS: Patients with a microbiologic diagnosis of bacterial keratitis were included in this double-masked, parallel-group study and were randomized to treatment with either ofloxacin 0.3% or ciprofloxacin 0.3% ophthalmic solution. One drop of the study medication was instilled during the daytime according to the following schedule: every half-hour on study day 1, every hour on days 2 through 4, and every 2 hours on days 5 through 21. Healing, the primary outcome measure, was defined as complete reepithelialization, accompanied by nonprogression of stromal infiltrate for 2 days. Secondary outcome measures included signs and symptoms of infection. Patients were monitored throughout the study period for any adverse events. RESULTS: A total of 217 patients completed the study: 112 were treated with ofloxacin and 105 were treated with ciprofloxacin. Streptococcus pneumoniae was the most commonly encountered pathogen in all patients. Complete corneal reepithelialization occurred in 85% of those treated with ofloxacin and in 77% of those treated with ciprofloxacin (p = 0.32). The average time to corneal ulcer healing was 13.7 days in those treated with ofloxacin and 14.4 days in those treated with ciprofloxacin. Both treatments were well tolerated with no patient discontinuing the study because of side effects. CONCLUSION: Ofloxacin 0.3% and ciprofloxacin 0.3% ophthalmic solutions are effective and safe in the treatment of patients with culture-positive bacterial keratitis.     

Effect of topical ciprofloxacin 0.3% and ofloxacin 0.3% on the reduction of bacterial flora on the human conjunctiva

PURPOSE: To evaluate quantitatively over time the reduction in bacterial flora on the human conjunctiva after treatment with topical ciprofloxacin 0.3% (Ciloxan) or topical ofloxacin 0.3% (Ocuflox). SETTING: Sinai Hospital of Baltimore, Baltimore, Maryland, USA. METHODS: Three study arms each consisted of 20 culture-positive eyes from patients 55 years or older. Pretreatment cultures were performed in all eyes. Eyes in the ciprofloxacin and ofloxacin arms received 1 antibiotic drop every 5 minutes for 3 doses. The conjunctiva of each treatment eye was recultured 15, 30, 60, and 120 minutes after application of the final antibiotic drop. Eyes in the control arm were recultured at corresponding time points. After 48 hours of incubation, colony counts were performed. Data were transformed into log units, and statistical analysis was performed.When compared to no treatment, instillation of ofloxacin 0.3% did not produce a significant reduction in bacterial colony forming units (CFUs) at 15, 30, or 60 minutes (P =.17). A marginally significant reduction was achieved 120 minutes after administration (P =.051). RESULTS: When compared to no treatment, instillation of ciprofloxacin 0.3% produced a significant reduction in bacterial CFUs at 15 minutes; this effect persisted for at least 2 hours (P <.0001). The reduction in bacterial CFUs by ciprofloxacin was significantly greater than that by ofloxacin at all measurements (P <.0001). CONCLUSIONS: Ciprofloxacin 0.3% markedly reduced bacterial flora on the ocular surface within 15 minutes of instillation, and the effect lasted for at least 2 hours.     

Comparison of topical itraconazole 1% with topical natamycin 5% for the treatment of filamentous fungal keratitis

PURPOSE: To compare the clinical efficacy of itraconazole 1% eyedrops with a standard therapy regimen (natamycin 5% eyedrops) for topical monotherapy of fungal keratitis. METHODS: Patients presenting with suspected uniocular microbial keratitis over a period of 12 months (January to December 2002) underwent detailed clinical examination and microbiological investigation. One hundred consecutive patients with direct smear- and/or culture-proven fungal keratitis were enrolled in the study after obtaining informed consent. The ulcers were categorized as severe or nonsevere. The first 50 consecutive patients received primary therapy with topical natamycin hourly, and the next 50 consecutive patients received topical itraconazole hourly. The primary efficacy criteria were the physician's judgment of clinical success, cure rate, and the rate of treatment failure. RESULTS: The diagnosis of fungal keratitis was established by positive microscopy and culture findings in 88 patients and by positive microscopy alone in 12 patients. Species of Fusarium, Aspergillus, and Curvularia were the principal isolates. Thirty-six (72%) of 50 patients (28 of 37 with nonsevere keratitis and 8 of 13 with severe keratitis) showed a favorable response to primary natamycin therapy (mean duration, 20.5 days), while 30 (60%) of 150 patients (25 of 38 with nonsevere keratitis and 5 of 12 with severe keratitis) exhibited a favorable response to primary itraconazole therapy (mean duration, 23.1 days). In keratitis due to Fusarium spp, 19 (79%) of 24 patients showed a favorable response to natamycin, which was significantly greater than the 8 (44%) of 18 patients who showed a favorable response to itraconazole (P < 0.02). However, no such difference was evident in keratitis due to Aspergillus spp or Curvularia spp; in keratitis due to Aspergillus spp, favorable responses were noted in 6 (54.5%) of 11 patients receiving natamycin and 5 (50%) of 10 patients receiving itraconazole, while in keratitis due to Curvurlaria spp, such responses occurred in both patients receiving natamycin and in 8 (89%) of 9 patients receiving itraconazole. Both antifungal formulations were generally well tolerated with no obvious adverse effects. CONCLUSIONS: Topical natamycin should continue to be considered as the treatment of choice for filamentous fungal keratitis; when natamycin is unavailable, topical itraconazole therapy could be used, particularly if the infections are due to Aspergillus or Curvularia spp.     

Treatment of acute bacterial conjunctivitis with topical lomefloxacin 0.3% compared to topical ofloxacin 0.3%

PURPOSE: The main purpose of this prospective study was to compare the efficacy, local tolerance, and safety of topical lomefloxacin 0.3% and topical ofloxacin 0.3% in the treatment of acute bacterial conjunctivitis. PATIENTS AND METHODS: Forty patients with acute bacterial conjunctivitis were included in a randomized, prospective, parallel-group study. Twenty patients were assigned to the lomefloxacin group (Okacin, CIBA Vision Ophthalmics) and 20 patients to ofloxacin (Oflox, Allergan). Lomefloxacin 0.3% was given 1 drop every 2 hours during waking hours on the first day then twice daily for one week. Ofloxacin 0.3% eyedrops were given four times daily. All patients underwent eye examination and clinical findings were graded and recorded according to severity of lid hyperemia, lid edema, lid crusting, conjunctival edema and discharge, bulbar conjunctival hyperemia, palpebral conjunctival hyperemia, corneal edema, and ocular discomfort. The score for each clinical sign was recorded before and after treatment. The mean cumulative sum score (CSS) was obtained by adding the scores for signs and symptoms. All conjunctival swabs were cultured and tested for sensitivity. Patients with confirmed bacterial conjunctivitis were included. RESULTS: There were 10 male and 10 female patients in each group. The age range was from 1 to 78 years, and the mean age was 35 years in the lomefloxacin group. In the ofloxacin group the age range was from 1 to 70 years, and the mean age was 26 years. There was no significant difference between the two groups in relation to age or sex. The causative organisms were Staphylococcus epidermidis in 16 cases (36%), alpha-hemolytic Streptococci in 9 (20%), Haemophilus spp. 6 (13%), Staphylococcus aureus 5 (11%), Streptococcus pneumoniae 4 (9%), Pseudomonas aeruginosa 3 (7%), and other 2 (4%). The mean CSS for conjunctivitis was 12.1 before therapy in the lomefloxacin group and 12.7 in the ofloxacin group. On the 7th day of therapy, the mean CSS was 0.7 in the lomefloxacin group, and 1.6 for ofloxacin. All patients showed improvement, but a total of 18 out of 20 (88%) in the lomefloxacin group showed complete resolution compared to 15 (75%) in the ofloxacin group. The difference was not statistically significant (p = 0.08). Tolerance was excellent in both groups, and no side effects were reported. A burning sensation was noted by two patients, one in each group. CONCLUSIONS: Lomefloxacin and ofloxacin were equally effective and safe in the treatment of acute bacterial conjunctivitis.     

0.5%左氧氟沙星与0.3%加替沙星及0.3%乳酸左氧氟沙星的房水药物浓度研究

目的 探讨人眼分别滴用0.5%左氧氟沙星、0.3%加替沙星及0.3%乳酸左氧氟沙星后房水中药物浓度差异.方法 采用随机、双盲、平行研究方法.选取2006年8月至2007年2月在浙江大学医学院附属第二医院眼科中心预行白内障超声乳化术的老年白内障患者150例(150只单侧眼),使用随机数字表法分为3个大组:0.5%左氧氟沙星组(50只眼)、0.3%加替沙星组(50只眼)、0.3%乳酸左氧氟沙星组(50只眼),每个大组冉使用随机排列表分为5个亚组,每个亚组10只眼.按不同大组,术前分别局部给予0.5%左氧氟沙星、0.3%加替沙星或0.3%乳酸左氧氟沙星滴眼,总共4次,每次间隔15 min.手术时按不同亚组,分别于最后1次给药后15、30、60、120、180 min时抽取房水多于100 μl,然后用加样器准确定量至100μl置于带塞试管中.全部标本采用高效液相色谱法测定房水中药物浓度.采用单因素方差分析(ANOVA)对不同时间点的3种药物浓度进行统计学分析,两两之间差异比较采用t检验进行分析.结果 给药后15、30、60、120、180 min房水内0.5%左氧氟沙星浓度(1.61±0.48)、(2.41±0.80)、(2.93±0.50)、(2.56±0.63)、(1.87±0.88)mg/L分别高于对应时间点的0.3%加替沙星浓度(0.70±0.18)、(1.29±0.54)、(1.59±0.67)、(1.41±0.50)、(1.13±0.28)mg/L及0.3%乳酸左氧氟沙星浓度(0.55±0.39)、(1.15±0.42)、(1.38±0.49)、(1.02±0.33)、(0.55±0.31)m.g/L,差异均有统计学意义(F=23.64,12.82,21.13,25.00,12.22;P均<0.05).0.3%加替沙星和0.3%乳酸左氧氟沙星的房水药物浓度经检验在15、30、60、120 min无明显差异(t=1.09,0.68,0.83,2.00;均P>0.05).在180 min时0.3%加替沙星的房水药物浓度高于0.3%乳酸左氧氟沙星,差异有统计学意义(t=4.36,P<0.05).结论 人眼滴用0.5%左氧氟沙星、0.3%加替沙星及0.3%乳酸左氧氟沙星后,以滴用0.5%左氧氟沙星后房水的药物浓度最高.     

Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty

PURPOSE: To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty. METHODS: In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups. RESULTS: The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 microg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 mug.h/g (P < 0.05). The endothelial Cmax was 76.1 versus 7.3 microg/g (P > 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 microg.h/g (P < 0.05). The aqueous Cmax was 0.9 versus 0.3 microg/mL (P > 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 microg.h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups. CONCLUSIONS: Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.     

Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.

AIMS--This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. METHODS--Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3% topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. RESULTS--Intracorneal concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ significantly (p = 0.33). CONCLUSIONS--Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin.     

The successful treatment of gatifloxacin-resistant Staphylococcus aureus keratitis with Zymar (gatifloxacin 0.3%) in a NZW rabbit model

PURPOSE: To determine whether gatifloxacin-resistant S. aureus (Gat-R-Sa) keratitis could be successfully treated with topical Zymar (gatifloxacin 0.3%) in a rabbit model. DESIGN: Experimental animal study. METHODS: Two separate studies were performed each using two clinical isolates of Gat-R-Sa, with MICs of 12 and 64 mug/ml to gatifloxacin. Study 1 consisted of four treatment groups (Zymar, Quixin [levofloxacin 0.5%], Ciloxan [ciprofloxacin 0.3%], and saline).Study 2 consisted of Zymar, cefazolin 50 mg/ml, vancomycin 50 mg/ml, and saline. Rabbits were infected intrastromally with 2,000 cfu in both eyes. Topical therapy began after four hours, every 15 minutes for 5 hours. After therapy, the eyes were graded for clinical signs of infection (blepharitis, conjunctivitis, iritis, corneal edema, and corneal infiltrates), and the corneas were homogenized to determine viable bacterial counts. RESULTS: Study 1: for both isolates, Zymar-treated eyes demonstrated significantly lower clinical scores compared with Ciloxan and saline, and significantly decreased the number of viable bacteria recovered compared with all groups. Study 2: for both isolates, Zymar and cefazolin demonstrated significantly lower clinical scores compared with vancomycin and saline. Zymar, cefazolin, and vancomycin significantly decreased the number of viable bacteria recovered compared with the saline control. CONCLUSIONS: We demonstrated the "Proof of Principle" that in vitro antibiotic resistance, based on CLSI standards, does not always correlate with in vivo treatment failure in the eye. An aggressive treatment regimen with Zymar appears to overcome in vitro resistance, resulting in the successful treatment of Gat-R-Sa infections in the NZW rabbit keratitis model.     

Corneal ciprofloxacin precipitation during bacterial keratitis

PURPOSE: To examine how age affects the risk of developing a white corneal precipitate during ciprofloxacin therapy for bacterial keratitis and to explore the effect of a white precipitate on rates of clinical improvement and cure. DESIGN: Prospective, multicenter, observational cohort study. METHODS: Occurrence of a white precipitate of the corneal surface was recorded among 624 patients with presumed bacterial keratitis who were treated with topical ciprofloxacin 0.3% solution or ointment. Relative risks of corneal precipitation were estimated from logistic regression for age categories and other clinical characteristics. The time-dependent effects of precipitate on rates of infection resolution and corneal reepithelialization were estimated by proportional hazards regression. RESULTS: Ninety-five (15.2%) patients developed a white corneal precipitate during ciprofloxacin therapy; 72 (75.8%) began within the first 3 days of treatment. Compared with those younger than 40 years old, patients aged 60 to 69 years had 2.8 (95% confidence limits [CL], 1.9, 3.9) times the risk of ciprofloxacin precipitation; patients 70 years and older had 3.7 (95% CL, 2.6, 5.0) times the risk. Median duration of the visible corneal precipitate was 8.5 days (90% decile, 32 days). Presence of ciprofloxacin precipitation did not significantly affect the time until therapeutic improvement (P =.09) but slowed the time until reepithelialization by 55% (95% CL 32%, 70%). CONCLUSIONS: Older patients treated with topical ciprofloxacin for bacterial keratitis have a higher risk of corneal deposition. A white precipitate apparently does not interfere with antibacterial therapeutic response but may delay epithelial healing of ulcerative keratitis.     

The efficacy of topical ciprofloxacin and norfloxacin in the treatment of experimental Pseudomonas keratitis

An aminoglycoside-resistant strain of Pseudomonas aeruginosa was injected intrastromally into the corneas of rabbits, and keratitis was allowed to develop over a 22-h period. Rabbits were treated with either 0.75% ciprofloxacin, 1% norfloxacin, or 1.36% tobramycin administered topically every 15 min for 1 h and then every 30 min for the following 3 h. All therapy ceased 26 h postinoculation. Rabbits were killed 1 h after the treatment, and the number of bacteria per cornea were quantified in terms of bacterial colony-forming units. Aqueous humor specimens were obtained from rabbits receiving norfloxacin and ciprofloxacin, and bioassays were performed to determine drug concentration. Ciprofloxacin caused a 5 log reduction in the number of bacterial colony-forming units, as compared with untreated controls (p less than 0.0001); it also produced a significantly greater reduction in bacterial colony-forming units than either norfloxacin or fortified tobramycin drops (p less than 0.0001). Norfloxacin produced a 2 log reduction in bacterial colony-forming units, as compared with untreated controls (p less than 0.0001). The mean aqueous concentration of norfloxacin (7.5 micrograms/ml) was substantially less than that achieved by ciprofloxacin (30.5 micrograms/ml). We conclude that ciprofloxacin may be a useful broad spectrum, topical chemotherapeutic agent in the therapy of aminoglycoside-resistant P. aeruginosa keratitis.     

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.     

Comparison of in vitro susceptibilities of ocular bacterial isolates to gatifloxacin and other topical antibiotics

PURPOSE: To compare the in vitro activity of gatifloxacin with that of other topical antibiotics against fresh bacterial isolates from various types of human ocular infections. METHODS: A total of 498 strains of ocular bacterial isolates were tested for their susceptibility to gatifloxacin, ofloxacin, ciprofloxacin, norfloxacin, gentamicin, tobramycin, neomycin, chloramphenicol, erythromycin, tetracycline and amikacin. RESULTS: Ninety-nine percent of gram-positive and 92% of gram-negative bacterial strains were found to be susceptible in vitro to gatifloxacin, whereas lower percentages of gram-positive and gram-negative bacteria were found to be susceptible to other antibiotics. CONCLUSIONS: In vitro, gatifloxacin exhibits good activity against various bacterial species isolated from different ocular sites. This requires corroboration in the clinical setting.     

Evaluation of topical 0.03% flurbiprofen drops in the treatment of herpetic stromal keratitis

Purpose: The management protocol for herpetic stromal keratitis (HSK) is still controversial. We have attempted to compare the relative efficacy of topical dexamethasone 0.01 % and flurbiprofen 0.03% in combination with topical acyclovir 3% in HSK.
Methods: In this institutional, prospective, randomized, controlled, double-blind study, 45 clinically diagnosed cases of HSK were randomly distributed into three coded treatment groups — topical placebo, dexamethasone 0.01 %, and flurbiprofen 0.03% each in tapering frequency and in combination with acyclovir 3% ointment five times per day for four weeks. Therapeutic response was assessed every third day for four weeks. Decoding of the treatment groups was done at the conclusion of the study and data analysed.
Results: Four-week success rate was 93.3% (14 of 15) in the dexamethasone-acyclovir treatment group, 66.7% (10 of 15) in the flurbiprofen-acyclovir treatment group and 20% (3 of 15) in the placeboacyclovir treatment group.
Conclusion: While dexamethasone in combination with acyclovir gives the best results in HSK with minimal side-effects, the role of topical flurbiprofen seems promising.