Treating with besifloxacin for acute bacterial conjunctivitis: a Meta-analysis

AIM: To evaluate the relative efficacy and safety of besifloxacin for treatment of acute bacterial conjunctivitis. METHODS: A comprehensive search in PubMed, EMBASE Web of Science, Cochrane Central Database and CNKI was undertaken for randomized controlled trials (RCTs) comparing besifloxacin with other treatments or placebo. The primary outcome measures were clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, and bacterial eradication rates of different kinds of pathogens. Safety outcomes were the number of adverse effects (AEs). The final search was performed on August 2018. RESULTS: Six RCTs were included. Four studies compared the efficacy and safety of besifloxacin with placebo, 1 study compared besifloxacin with moxifloxacin, and 1 study compared besifloxacin with gatifloxacin. A total of 2780 patients met the inclusion criteria. Besifloxacin presented higher efficacy and safety than did placebo in clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, bacterial eradication rates of different kinds of pathogens and the number of AEs. There was no significant difference between besifloxacin and moxifloxacin or gatifloxacin in the comparison items mentioned above. CONCLUSION: Besifloxacin is highly effective and safe for treatment of acute bacterial conjunctivitis. Further comparative trials regarding the effect of besifloxacin for treatment of acute bacterial conjunctivitis will aid in treatment decisions.     

加替沙星和左氧氟沙星对急性细菌性结膜炎有效性与安全性的Meta分析

目的:运用Meta分析系统评价加替沙星滴眼液和左氧氟沙星滴眼液对急性细菌性结膜炎的临床疗效及安全性。方法:按Cochrane系统评价方法,以“加替沙星”“左氧氟沙星”“急性细菌性结膜炎”为关键词,检索Embase、Cochrane library、Pubmed、Medline、中国知网数据库、万方数据库、维普中文科技期刊数据库、中国生物医学文献数据库,从建库开始时间检索至2021-03-01。纳入比较加替沙星滴眼液和左氧氟沙星滴眼液治疗急性细菌性结膜炎的随机对照研究。采用Cochrane偏倚风险评估工具对纳入研究进行质量评价,使用RevMan5.3统计软件进行Meta分析,运用Stata12中Egger检验分析发表性偏倚,并按照GRADE系统评估证据水平。结果:共纳入10项随机对照研究,合计1149例患者。对照组采用左氧氟沙星滴眼液治疗,试验组采用加替沙星滴眼液滴眼液治疗。Meta分析结果表明加替沙星滴眼液组对于急性细菌性结膜炎临床有效率优于左氧氟沙星滴眼液组(OR=3.75,95%CI:2.52~5.58,P<0.00001),Egger检验提示存在发表偏倚,且GRADE评价结果显示该证据水平为“很低”;加替沙星滴眼液组药物不良反应发生率低于左氧氟沙星滴眼液组(OR=0.37,95%CI:0.19~0.71,P=0.003);Egger检验提示不存在发表偏倚,且根据GRADE方法评价,该证据水平为“低”。结论:加替沙星滴眼液对于急性细菌性结膜炎的疗效优于左氧氟沙星滴眼液,且不良反应发生率较低;但由于纳入的研究证据水平较低,需要更多的多中心、随机双盲临床试验,从而提高加替沙星滴眼液治疗急性细菌性结膜炎临床疗效的证据强度。     

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.     

加替沙星对比左氧氟沙星治疗细菌性结膜炎疗效与安全性的Meta分析

目的  系统评价加替沙星对比左氧氟沙星治疗细菌性结膜炎疗效与安全性。设计 系统综述。研究对象 检索中国生物医学文献数据库、中国期刊全文数据库（CNKI）、万方医药期刊全文数据库、中文科技期刊数据库、PubMed、Cochrane Library、 Embase。收集加替沙星对比左氧氟沙星治疗细菌性结膜炎的临床随机对照研究（RCT）。方法 根据纳入和排除标准筛选文献,对符合条件的RCT由两位研究者独立进行资料提取和质量评价后,采用Cochrane协作网提供的RevMan 5.3与Stata12.0进行Meta分析。主要指标 治愈率、痊愈率、不良反应。 结果  加替沙星组治愈率（OR＝3.20,95%CI为2.37~4.31,P＜0.00001）与痊愈率（OR＝1.88,95%CI为1.56~2.27,P＜0.00001）较左氧氟沙星组均较高,并能降低总不良反应的发生（OR＝0.47,95%CI为0.27~0.80,P=0.006）。而眼睛刺痛（OR＝0.76,95%CI为0.37~1.57,P=0.46）、眼痒（OR＝0.32,95%CI为0.10~1.00,P=0.05）等不良反应指标在两组中无差异。结论 加替沙星在治疗细菌性结膜炎方面,与左氧氟沙星相比疗效好,不良反应少。     

A clinical comparison of two formulations of tobramycin 0.3% eyedrops in the treatment of acute bacterial conjunctivitis

PURPOSE: To compare the safety and efficacy of a new enhanced viscosity ophthalmic formulation of tobramycin, given twice daily (BID), with the existing four times daily (QID) treatment regimen in patients with acute bacterial conjunctivitis. METHODS: This was a 12-day, multicenter, observer-masked, randomized, parallel group study. Patients received one drop of tobramycin 0.3% (3 mg/mL) enhanced viscosity ophthalmic solution BID or tobramycin 0.3% (3 mg/mL) ophthalmic solution QID in the affected eyes for 7 days. The primary efficacy variable was the percentage of patients with sustained cure/presumed bacterial eradication based on clinical judgment at the test-of-cure visit (Day 12). Pretherapy bacterial isolates were obtained and tested for susceptibility to tobramycin by determination of minimum inhibitory concentrations (MIC). RESULTS: A total of 276 patients were enrolled in the study and 203 of these were culture positive and attended all follow-up examinations. In this group, 98% of those treated with tobramycin enhanced viscosity ophthalmic solution and 99% of those treated with tobramycin 0.3% ophthalmic solution were categorized as having sustained cure/presumed eradication at the test-of-cure visit (p = 0.6037). Reported adverse events were not serious, mild to moderate in severity, and generally did not prevent continuation in the study. Several pre treatment pathogens demonstrated tobramycin resistance (MIC > 4 mg/mL). However, therapy with both treatments was effective in the majority of the cases. CONCLUSIONS: Tobramycin enhanced viscosity ophthalmic solution is well tolerated and has equivalent efficacy to the established treatment regimen with a simplified posology. The formulation provides an alternative therapy for acute bacterial conjunctivitis that should improve patient compliance and satisfaction.     

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 Case Report of Severe Corneal Toxicity following 0.5% Topical Moxifloxacin Use

Moxifloxacin is a widely used topical antibiotic in various bacterial infections of the eye. Its safety and efficacy have been proved by many studies. We report a case of a rare adverse effect following its use. A 10-year-old female who had presented with acute bacterial conjunctivitis in both eyes with no corneal involvement was started on preservative-free 0.5% topical moxifloxacin four times a day. The child developed a severe form of corneal toxicity in both eyes with circumcorneal congestion and corneal edema following its use. The child''s visual acuity had dropped from 20/20 to 20/400 in both the eyes. Topical moxifloxacin was discontinued, following which the cornea cleared dramatically and the visual acuity became normal. This case indicates that though rare, topical moxifloxacin can cause severe keratitis and that more studies need to be conducted to evaluate its safety.Key Words: Topical moxifloxacin, Fluoroquinolones, Keratitis     

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.     

加替沙星滴眼液治疗细菌性结膜炎临床分析

目的 探讨加替沙星滴眼液治疗细菌性结膜炎的临床效果.方法 加替沙星组和氧氟沙星组各为120例,合计240例.采用计算机编程随机法,随机双盲对照试验.患者的纳入应能满足所有入选及排除标准,随机分为加替沙星组和氧氟沙星组,分别给予加替沙星滴眼液和相同浓度对照药氧氟沙星滴眼液,疗程7～14天.加替沙星滴眼液组:每日5次,每次1～2滴,滴入结膜囊内,氧氟沙星滴眼液组:每日5次,每次1～2滴,滴入结膜囊内,随诊观察.结果 本研究共分离临床敛病菌67株,其对加替沙星、氧氟沙星、左氧氟沙星和环丙沙星的敏感率分别为98.51%、85.07%、95.52%、78.79%.表明加替沙星的细菌敏感率最高,与氧氟沙星比较,差异有统计学意义.加替沙星滴眼液治疗细菌性结膜炎的疗效不低于氧氟沙星滴眼液.结论 结果表明,加替沙星滴眼液抗菌谱广、抗菌活性强,与氧氟沙星滴眼液疗效相当,安全性好,适于作为细菌性结膜炎的治疗用药.同时对革兰阳性菌和革兰阴性菌感染的眼表疾病,都有一定的治疗效果.

Abstract：

Objective To study the clinical efficacy of gatifloxacin eye drops for bacterial conjunctivitis.Methods A total of 240 cases that diagnosed as bacterial conjunctivitis were randomly divided into test group (gatifloxacin) and control group (floxacin).A random double-blind and paralled study was conducted on 120 cases with gatifloxacin and floxacin eye drops for bacterial conjunctivitis.The drug delivery into conjunctival sac was performed at 7-14 days (one-two drops per time, five times per day).Results Sixty-seven clinical common pathogenic bacteria were separated from the study.The antibacterial activity of gatifloxacin,floxacin, levofloxacin, ciprofloxacin was 98.51%, 85.07%, 95.52%, and 78.79% respectively.The antibacterial activity of gatifloxacin was the highest, and the statistic difference between gatifloxacin and floxacin was found.The effect of gatifloxacin eye drops was not worse than floxacin eye drops.Conclusions The gatifloxacin eye drops has characteristics with broad spectrum, powerfull antibacterial activity.The linical effect of gatifloxacin eye drops is the same with floxacin eye drops.Gatifloxacin eye drops are safe and can be used to treat bacterial conjunctivitis.It has comparatively theropic value of ocular surface disease with Gram-positive bacterial and Gram-negetive bacterial.     

In vitro activity of fluoroquinolones against ocular bacterial isolates in São Paulo, Brazil

PURPOSE: To compare the in vitro susceptibility profiles of bacterial ocular isolates and to determine minimum inhibitory concentrations (MICs) of gatifloxacin and moxifloxacin (fourth-generation fluoroquinolones) versus ciprofloxacin and ofloxacin (second-generation fluoroquinolones). METHODS: Gram-positive and gram-negative isolates were recovered from cases of keratitis, conjunctivitis, and endophthalmitis between 2002 and 2004 and were identified and extracted from the Microbiology Data Bank of the Federal University of S?o Paulo, S?o Paulo, Brazil. The comparison of in vitro MIC and susceptibility profiles for ofloxacin, ciprofloxacin, gatifloxacin, and moxifloxacin in gram-positive and gram-negative (n = 219) isolates was performed using the E test method. RESULTS: The fourth-generation fluoroquinolones were statistically more potent than the second generations for gram-positive bacteria. The MIC90 level was lower for moxifloxacin than that for gatifloxacin against Staphylococcus aureus, methicillin-susceptible coagulase-negative Staphylococcus (CoNS), and S. pneumoniae, whereas the levels were equal against S. viridans and the gatifloxacin MIC90 was lower in methicillin-resistant CoNS. There was no statistically significant difference between moxifloxacin and gatifloxacin when the permutation method from the MULTTEST procedure (SAS proc multtest) was used to obtain the adjusted P value. MIC90 for ciprofloxacin was lower in gram-negative bacteria. MIC90 for ofloxacin was higher against Haemophilus spp. and Moraxella spp. Ciprofloxacin was the most statistically potent fluoroquinolone for Pseudomonas spp. Ciprofloxacin was statistically just as potent as gatifloxacin for the other gram-negative isolates. CONCLUSION: From susceptibility profiles achieved with in vitro testing, the fourth-generation fluoroquinolones may offer some advantages over the currently available fluoroquinolones; however, a combination of the pharmacodynamics and pharmacokinetics of the drug, infection site, and the MIC is needed to predict the in vivo efficacy and best clinical applicability.     

Overview of the potency of moxifloxacin ophthalmic solution 0.5% (VIGAMOX)

Antibiotics have been the mainstay of therapy for infectious diseases since their origins in the 1940s. As microorganisms changed and resistance developed, more advanced antibiotics were ultimately needed to provide adequate coverage and spectrum. By selecting optimal antibiotics and dosing regimens, clinicians can avoid treatment failures and adverse events and can help prevent the emergence of further antibiotic resistance. The fourth-generation ophthalmic fluoroquinolones include moxifloxacin (VIGAMOX, Alcon Laboratories, Inc., Fort Worth, TX) and gatifloxacin (Zymar, Allergan, Irvine, CA), and they are now approved for the treatment of bacterial conjunctivitis. This review highlights four scientific methods that compare and rank antibiotic potencies and predict their clinical efficacy and their propensity to develop resistance: 1) in vitro assay for minimum inhibitory concentrations, 2) in vivo models for pharmacokinetic and pharamacodynamic properties, 3) therapeutic index or inhibitory quotient, and 4) in vitro assay for mutant prevention concentration. The fourth-generation ophthalmic fluoroquinolones perform well in these assays. Both antibiotics have better in vitro activity against gram-positive bacteria than ciprofloxacin or ofloxacin. Moxifloxacin penetrates better into ocular tissues than gatifloxacin and older fluoroquinolones; in vitro activity of moxifloxacin and gatifloxacin against gram-negative bacteria is similar to that of older fluoroquinolones. Moxifloxacin also has better mutant prevention characteristics than other fluoroquinolones. These findings support the use of the newer fluoroquinolones for the prevention and treatment of serious ophthalmic infections (e.g., keratitis, endophthalmitis) caused by susceptible bacteria.     

新生儿急性细菌性结膜炎10年致病菌变迁

对1998～2007年临床确诊的新生儿急性细菌性结膜炎的细菌培养结果进行分析,探讨其致病菌10年的变迁,为临床治疗、合理用药提供依据.方法 对325例(466只眼)经临床诊断为新生儿急性细菌性结膜炎患儿的结膜囊分泌物标本进行细菌培养,同时对培养阳性的菌株进行鉴定分析.结果 新生儿急性细菌性结膜炎的细菌平均检出率为80%.不同年分的细菌检出率变化无明显差异(x2=0.83,P＞0.05).10年来,新生儿急性细菌性结膜炎的致病菌中革兰阳性细菌有逐渐减少、革兰阴性细菌有逐渐增加的趋势.在革兰阳性细菌中,条件致病菌(表皮葡萄球菌和腐生匍萄球菌)所占的百分比有逐年增加的趋势,金黄色葡萄球菌和溶血性链球菌所占的百分比则有逐年减少的趋势.在革兰阴性菌中,淋球菌为主要致病菌.10年来,表皮葡萄球菌、腐生葡萄球菌和淋球菌在新生儿急性细菌性结膜炎的致病菌中有逐渐增加的趋势.结论 对新生儿急性细菌性结膜炎患儿的结膜囊分泌物标本进行细菌培养、药物敏感试验既助于提高临床治疗,又可防止临床滥用抗生素、造成耐药菌株的增加.对于严重的新生儿急性细菌性结膜炎,早期可慎片喹诺酮类抗生素滴眼液治疗,待细菌培养和药物敏感试验结果报告后再结合治疗情况修改治疗方案.

Abstract：

Objective To study the results of bacterial culture from the inferior palpebral conjunctival surface of neonate with acute bacterial conjunctivitis and research the transition of bacterial pathogens in recent 10 years for sensitive antibiotics for its treatment,and to provide the basis for rational drug use for clinical treatment.Methods Secretion specimens were taken from 466 eyes of 325 cases with clinically diagnosed acute bacterial neonatal conjunctivitis for bacterial culture,and drug sensitivity test was carried out for specimens with positive culture results.Results Bacterial positive rate was 80% with insignificant changes among the different years.The past 10 years,neonatal conjunctivitis of acute bacterial pathogens,Gram-positive bacteria had a gradual downward trend;Gram-negative bacteria had a gradual upward trend.In Gram-positive bacteria,the percentage of opportunistic pathogen (Staphylococcus epidermidis and Staphylococcus saprophytic) was a rising trend,the percentage of Staphylococcus anreus and hemolytic streptococcus was a decreasing trend.In the Gram-negative bacteria,the main pathogenic bacteria were Neisseria gonorrhoeae.Staphylococcus epidermidis,Staphylococcus saprophytic and Neisseria gonorrhoeae in neonatal pathogens of acute bacterial conjunctivitis had a gradual upward trend in recent 10 years.Conclusions Bacterial culture combined with drug sensitivity test of secretion specimens of the acute bacterial neonatal conjunctivitis are beneficial not only for clinical treatment,but also to guide clinical practice in preventing antibiotics misuse and causing an increase in resistant strains.For serious neonatal acute bacterial conjunctivitis,the early quinolone antibiotic eye drops can be used with caution.After the results of bacterial culture and drug sensitivity test,the treatment programs should be modified.     

Acute endophthalmitis in eyes treated prophylactically with gatifloxacin and moxifloxacin

PURPOSE: To study the use of prophylactic fourth-generation fluoroquinolone antibiotics, gatifloxacin and moxifloxacin, and bacterial sensitivity in cases of acute postoperative endophthalmitis following cataract surgery. DESIGN: Retrospective, consecutive, observational case series. METHODS: Forty-two eyes of 42 patients with acute endophthalmitis occurring within six weeks after cataract surgery were identified. All patients were seen in a referral vitreoretinal practice over a two-year time interval. The number of patients using prophylactic gatifloxacin or moxifloxacin and results of bacterial culture and sensitivity to all fluoroquinolone antibiotics were recorded. RESULTS: Thirty-one of 42 eyes (74%) were treated with perioperative gatifloxacin or moxifloxacin and 24 eyes (57%) were continuously taking one of these antibiotics at the time of diagnosis. Nineteen eyes (45%) had a positive bacterial culture. The most frequent organism isolated was coagulase-negative Staphylococcus. Sensitivities were performed for 14 gram-positive organisms, and sensitivities to ciprofloxacin (50%), ofloxacin (44%), levofloxacin (46%), gatifloxacin (38%), and moxifloxacin (38%) were noted. Five organisms were resistant to gatifloxacin and moxifloxacin with a minimum inhibitory concentration of 8 microg/ml. All gram-positive organisms were sensitive to vancomycin. Median visual acuity improved from hand motions to 20/40 at last follow-up. CONCLUSION: Acute endophthalmitis can develop after cataract surgery despite the prophylactic use of fourth-generation fluoroquinolone antibiotics. Gram-positive organisms causing acute endophthalmitis are frequently resistant to all fluoroquinolones, including a significant number of cases resistant to gatifloxacin and moxifloxacin.     

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.     

Nedocromil sodium 2% ophthalmic solution for the treatment of ragweed pollen seasonal allergic conjunctivitis

PURPOSE: To determine the efficacy and safety of nedocromil sodium 2% ophthalmic solution in the treatment of seasonal allergic conjunctivitis. METHODS: A combined analysis of two multicenter, randomized, comparative, double-masked, placebo-controlled clinical trials involving 261 patients diagnosed with seasonal allergic conjunctivitis was used. Patients were randomly assigned to receive either topical 2% nedocromil sodium or placebo twice daily for eight weeks. Diary card scores and clinician assessments of allergic symptoms were recorded throughout the study; efficacy was determined by comparing symptom severity at the peak pollen period with symptom severity at baseline. Clinician and patient evaluations of treatment effectiveness were used as secondary measurements of efficacy. RESULTS: Patients treated with nedocromil sodium experienced improvement in allergy symptoms, with reductions in the summary symptom score, itch, redness, conjunctival injection, and conjunctival edema significantly (p&lt;0.05) greater than those observed in the patients treated with placebo. Clinicians' and patients' opinions of nedocromil sodium treatment effectiveness were significantly (p&lt;0.02) superior to those of placebo treatment effectiveness. CONCLUSION: Nedocromil sodium is effective in the management of seasonal allergic conjunctivitis.     

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.).     

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.     

双氯芬酸钠透明质酸钠滴眼液治疗急性变态反应性结膜炎评价

目的 评价0.1%双氯芬酸钠透明质酸钠滴眼液辅助治疗急性变态反应性结膜炎的有效性及安全性的临床评价.方法 对90例(180只眼)急性变态反应性结膜炎患者.包括季节性与常年性变态反应性结膜炎,随机分成三组.A组:对照一组,单用0.05%依美斯汀滴眼液;B组:对照二组,0.05%依美斯汀滴眼液联合0.1%普拉洛芬滴眼液;C组:试验组0.05%依美斯汀滴眼液联合0.1%双氯芬酸钠透明质酸钠滴眼液,三组每种用药均为每日3次.分别于治疗前与治疗后1d、4d、7d、14d随访,评估眼痒、流泪、畏光、异物感等症状与睑结膜乳头和滤泡、分泌物、结膜充血、结膜水肿、角膜缘改变、角膜上皮改变、球周组织水肿等体征,评价有效率及治愈率,并观察用药后眼部不适及副反应.结果 三组患者的一般情况、治疗前症状与体征评分差异均无统计学意义(P＞0.05).A组、B组与C组的治疗有效率在治疗后第1天分别为6.7%、56.7%与60.0%,第4天分别为20.0%、100.0%与96.7%,第7天分别为53.3%、100.0%与100.0%,第14天分别为73.3%、100.0%与100.0%.治疗第14天治愈率分别为10.0%、73.3%与63.3%.两两比较各随访时间点的有效率与治愈率,A组与B组的组间差异均具有统计学意义(P均＝0.000),A组与C组组间的差异均具有统计学意义(P均=0.000),而B组与C组在治疗后各随访时间点的有效率与治愈率相当,差异无统计学意义(P=0.918、0.147、0.058、0.0405＞0.05).各试验组未见用药后的眼部不适及副反应.结论 非甾体类消炎药能快速、有效缓解急性变态反应性结膜炎的症状与体征,其中,0.1%双氯芬酸钠透明质酸钠滴眼液与同类进口滴眼液的疗效相当,是一种有效、安全又经济的变态反应性结膜炎的辅助治疗药物.     

Fourth-generation fluoroquinolone-resistant bacterial keratitis after refractive surgery

We report the first 2 cases of bacterial keratitis resistant to fourth-generation fluoroquinolones after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). The first patient had Pseudomonas aeruginosa keratitis after PRK despite treatment with moxifloxacin. The second patient was on gatifloxacin post-LASIK when she had methicillin-resistant Staphylococcus aureus (MRSA) keratitis diagnosed. In both cases, culture susceptibilities showed isolates resistant to moxifloxacin and gatifloxacin, and treatment with topical aminoglycosides and surgical intervention was necessary to effect a cure. These cases show the potential limitations in the coverage of these antibiotics.