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.     

A multicenter randomized study of fusidic acid ophthalmic gel and rifamycine eyedrops in acute conjunctivitis

A total of 163 patients with acute, presumably bacterial, conjunctivitis were included in a randomized trial, comparing: 1% fusidic acid viscous eye drops, a new ophthalmic formulation of fusidic acid instilled twice daily with rifamycin eye drops, four times daily. Both drugs were given 7 days long. Bacterial origin of the conjunctivitis, mainly staphylococcal, was proved in 75% of the cases. Overall, at the end of the treatment, a satisfactory response, on bacteriological and clinical grounds, was recorded for 87.3 and 89.5% of the patients in the Fucidin gel and rifamycin groups respectively. 9 and 12% of the patients in each group respectively, had a clinical recurrence 15 days after the treatment. No significant difference between the groups clinically and bacteriologically was noted. Side effects, mainly burning and smarting were noted by the investigators in 8 and 11 patients treated by fusilic acid and rifamycin respectively. Two patients were taken out of the study in the rifamycin group because of allergy. The difference between the groups is not significant. The use of fusidic acid viscous eye drops as compared to rifamycin eye drops was judged significantly easier by the patients (P less than 0.02), especially because of the reduced number of applications, the lack of color, and the lase of application.     

重视变态反应性结膜炎治疗中非甾体抗炎药物的应用

近年来随着工业化进程的加快,变态反应性结膜炎的发生率逐渐升高.目前,变态反应性结膜炎的治疗以眼局部治疗为主,主要目的在于针对病因,减轻症状和预防并发症.变态反应性结膜炎的治疗药物包括抗组胺药、肥大细胞稳定剂、双效作用药物（稳定肥大细胞/抗组胺）、非甾体抗炎药（NSAIDs）、糖皮质激素及免疫抑制剂六大类.抗组胺药、肥大细胞稳定剂、双效作用药物的主要作用是减轻眼部瘙痒、结膜充血等症状和体征,也可用于急性变态反应性结膜炎患者,而NSAIDs、糖皮质激素及免疫抑制剂则用于症状严重患者或慢性病例.糖皮质激素类药物治疗变态反应性结膜炎效果显著,可作用于过敏反应的多个环节,但是长期应用可能会导致眼压升高、视力障碍、视野缺损和后囊下白内障,有角膜溃疡的患者更应谨慎使用.免疫抑制剂具有抑制免疫的作用,可抑制局部或机体异常的免疫反应,但由于价格较高及局部刺激性强等不良反应,故也不宜长期应用.NSAIDs具有良好的抗炎效果,作用温和,刺激性小,目前在眼表变态反应性结膜炎中广泛应用.     

Fucithalmic in acute conjunctivitis. Open, randomized comparison of fusidic acid, chloramphenicol and framycetin eye drops

Fucithalmic, which is 1% fusidic acid in a sustained-release eye preparation, was shown to be superior to both chloramphenicol eye drops and framycetin (Soframycin) eye drops in the treatment of bacterial conjunctivitis in Tanzania. The clinical success rate was 77/83 (93%) on fusidic acid compared with 22/46 (48% on chloramphenicol and 26/35 (74%) on framycetin (P less than or equal to 0.02). The better effect of fusidic acid could be ascribed to a much lower rate of in vitro resistance (17%) compared to chloramphenicol (58%) and framycetin (41%). Because of the low resistance rate to fusidic acid among eye pathogens, especially in areas of the world with a high resistance towards other commonly used eye anti-infectives, Fucithalmic given twice daily would seem to be a valuable new eye anti-infective.     

Topical antibiotic prophylaxis for cataract surgery: a controlled trial of fusidic acid and chloramphenicol

The effectiveness of topical fusidic acid 1%, in a viscous drop base, to reduce or eliminate ocular microflora in patients undergoing cataract surgery has been studied. Forty-two patients received fusidic acid on a double-blind basis and for comparison 21 patients were similarly assessed with topical chloramphenicol. A further 17 patients received no treatment other than subconjunctival cephazolin administered to all operated eyes at the time of surgery. Quantitative bacterial counts from the conjunctivae and lash lines of each patient were made 24 hours before surgery, on the morning of operation and again 48 hours after surgery. With a regimen of five administrations on the day prior to surgery, neither topical fusidic acid 1.0% nor chloramphenicol 0.5% produced clinically or statistically significant reductions of the ocular microflora. In contrast perioperative subconjunctival cephazolin effectively reduced or eliminated lid and conjunctival microflora following surgery. This study indicates that the effectiveness of a topical antibiotic preparation for overt ocular infection cannot be directly extrapolated to the effect on resident ocular microflora, at least with short-term use for presurgical prophylaxis.     

Topical antibiotic prophylaxis for cataract surgery: a controlled trial of fusidic acid and chloramphenicol

The effectiveness of topical fusidic acid 1%, in a viscous drop base, to reduce or eliminate ocular microflora in patients undergoing cataract surgery has been studied. Forty-two patients received fusidic acid on a double-blind basis and for comparison 21 patients were similarly assessed with topical chloramphenicol. A further 17 patients received no treatment other than subconjunctival cephazolin administered to all operated eyes at the time of surgery. Quantitative bacterial counts from the conjunctivae and lash lines of each patient were made 24 hours before surgery, on the morning of operation and again 48 hours after surgery. With a regimen of five administrations on the day prior to surgery, neither topical fusidic acid 1.0% nor chloramphenicol 0.5% produced clinically or statistically significant reductions of the ocular microflora. In contrast perioperative subconjunctival cephazolin effectively reduced or eliminated lid and conjunctival microflora following surgery. This study indicates that the effectiveness of a topical antibiotic preparation for overt ocular infection cannot be directly extrapolated to the effect on resident ocular microflora, at least with short-term use for presurgical prophylaxis.     

急性细菌性结膜炎治疗前后的眼表改变

目的观察急性细菌性结膜炎治疗前后的眼表改变,为进一步了解急性细菌性结膜炎病理过程及治疗提供依据。方法对51例(72眼)确诊为急性细菌性结膜炎者给予抗生素滴眼液治疗,分别于首次就诊当天、治疗后1周、2周、3周、1个月行患眼基础泪液分泌试验、泪膜破裂时间、角膜荧光素染色检查,对检查结果进行统计学分析。结果基础泪液分泌试验结果显示:首次就诊当天为(7.6±2.7)mm,治疗后1周、2周、3周、1个月分别为(5.8±2.7)mm、(8.8±3.5)mm、(9.3±2·4)mm、(11.9±3·4)mm,与正常人群12.5mm比较,治疗后1周、2周、3周差异均有显著统计学意义(均为P<0.01),治疗后1个月差异无统计学意义(P>0.05)。泪膜破裂时间结果显示:首次就诊当天为(6.8±3.0)s,治疗后1周、2周、3周、1个月分别为(6.2±2.6)s、(8.6±3.6)s、(8.4±4.0)s、(24.3±3.9)s,与正常人群25.0s比较,治疗后1周、2周、3周差异均有显著统计学意义(均为P<0.01),治疗后1个月差异无统计学意义(P>0.05)。角膜荧光素染色显示:首次就诊当天阳性49眼,治疗后1周、2周、3周、1个月阳性分别为50眼、36眼、30眼、10眼。结论急性细菌性结膜炎发病时及治疗恢复过程中会出现干眼症状的眼表改变,在治疗中可考虑使用药物进行改善。     

左旋氧氟沙星滴眼剂治疗细菌性结膜炎角膜炎的临床观察

目的：了解国产０．３％左旋氧氟沙星滴眼剂治疗急性细菌性结、角膜炎的临床疗效及毒副作用。方法：确诊病例分层随机加入实验组及对照组,对照药物为０．３％氧氟沙星滴眼剂,对比观察疗效及毒副作用并统计学分析。结果：１９９９年４月至１２月共观察１３２例,其中实验组６７例（结膜炎－Ａ组３７例,角膜炎－Ｃ组３０例）,对照组６５例（结膜炎－Ｂ组３５例,角膜炎－Ｄ组３０例）。各组细菌培养阳性率均为８０％以上,两组的痊     

Hydrogel, a new galenic form in ophthalmology

Good tolerance, long intervals of application and an excellent adhesion are the properties of viscous eye drops (Hydrogels). The use of fusidic acid as a hydrogel in the treatment of bacterial eye infections guarantees a long-lasting antibiotic concentration in tear fluid. When given twice daily, there will be sufficient concentration of the antibiotic in all important tissues of the eye and at the same time it increases the patient compliance.     

夫西地酸对常见革兰染色阳性细菌的药物敏感性实验研究

目的 探讨夫两地酸、万古霉素、妥布霉素及氧氟沙星对8种常见革兰染色阳性细菌的体外药物敏感性.方法 实验研究.选用首都医科大学附属北京同仁医院、北京同仁眼科中心、北京市眼科研究所微生物室保存的眼部100株革兰染色阳性细菌,按照眼部微生物标本常规方法收集并进行细菌培养和菌种鉴定,采用纸片扩散法观察100株细菌对夫西地酸、万古霉素、妥布霉素及氧氟沙星的药物敏感性.应用SPSS 11.5软件包中的四格表卡方检验进行统计分析.结果 体外培养阳性的革兰染色阳性细菌对妥布霉素、氧氟沙星、万古霉素及夫西地酸的总体敏感性百分比分别是55.0%、65.0%、98.0%及53.0%.万古霉素总体敏感性百分比高于妥布霉素、氧氟沙星及夫西地酸,差异有统计学意义(x2=51.425、36.113、54.737,P<0.05).常见葡萄球菌对夫西地酸的敏感性(85.5%)仅低于万古霉素(100.0%),差异有统计学意义(x2=6.605,P<0.05);但高于妥布霉素(58.2%)和氧氟沙星(54.5%),差异有统计学意义(x2=10.106、12.511,P<0.05).常见的链球菌对夫西地酸的敏感性(0.0%)低于万古霉素(100.0%)和氧氟沙星(85.0%),差异有统计学意义(x2=40.000、29.565,P<0.05);而和妥布霉素(15.0%)之间比较差异无统计学意义(x2=1.441,P>0.05).而革兰阳性杆菌和奴卡菌属对夫西地酸的敏感性百分比(24.0%)则低于另外3种抗生素(妥布霉素80.0%,氧氟沙星72.0%,万古霉素92.0%),差异有统计学意义(x2=23.727、22.430、11.538,P<0.05).结论 夫西地酸对葡萄球菌的抗菌作用较强,面对链球菌和革兰阳性杆菌的作用则明显较弱.     

Cardiac effects of different eyedrop preparations of timolol in rabbits.

Coadministration of phenylephrine and increasing solution viscosity can decrease systemic timolol absorption after eyedrop application. In this study, changes in the heart rate of rabbits after non-viscous (1 cP) and viscous timolol-phenylephrine (330 cP) solution were compared with those after control timolol eyedrops. The resting heart rate of rabbits was not influenced by control timolol eyedrops (0.6 mg/ml, 25 microliters in both eyes). In contrast, control timolol eyedrops antagonized greatly isoproterenol-induced tachycardia for 120 min. Timolol (0.6 mg/ml)-phenylephrine (0.8 mg/ml) eyedrops (25 microliters in both eyes) antagonized the chronotropic effect of isoproterenol less than control timolol eyedrops for the first 10 min. Compared to control timolol eyedrops, administration of viscous timolol (0.3 mg/ml)-phenylephrine (0.8 mg/ml) solution (25 microliters in both eyes) lowered systemic beta-blocking activity of timolol for 120 min. Previously we have shown that compared to non-viscous (1 cP) timolol (5.0 mg/ml) eyedrop (25 microliters), viscous (330 cP) timolol (2.5 mg/ml)-phenylephrine (0.8 mg/ml) solution (25 microliters) results in equal or increased timolol concentrations in the ocular tissues. All three timolol eyedrops antagonized the isoproterenol-induced tachycardia more than buffer solution but the onset of significant beta-blocking effect induced by eyedrops varied from 3 min (control eyedrop) to 40 min (viscous eyedrop). Our results indicate that possible cardiac effects of ophthalmic timolol can be diminished by phenylephrine coadministration and increased solution viscosity.     

In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter

BACKGROUND: Recent decades have been marked by an increasing number of patients suffering from ocular allergic-like symptoms without being associated with an increase in IgE levels. These symptoms include heaviness of the lid, foreign body sensation, burning, stinging and photophobia. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between allergic-like symptoms and environmental factors such as outdoor air pollutants or poor indoor air quality. An ocular surface subclinical inflammation is thought to be responsible for pseudoallergic, pollution-related conjunctivitis. The complement system is considered as one of the major effector mechanisms involved in initiation of the subclinical inflammation that leads to IgE-independent eye irritation. PURPOSE: To study the capability of nine antiallergic eyedrops commonly used in the treatment of allergic conjunctivitis to inhibit complement activation induced in vitro by pollutants. METHODS: Normal human serum obtained from healthy individuals was used as a source of complement. Activation of complement was assessed using the complement hemolytic 50% (CH50) assay, in the absence or the presence of antiallergic eyedrops and in the absence or the presence of various stimuli, including sand, common house dust, eye mascara, and Dactylis glomerata pollen extract. Zymosan was used as a standardized complement activator. The following eyedrops were studied: Naabak (4.9% N-acetyl aspartic acid-glutamic acid, NAAGA, sodium salt), Almide (lodoxamide 0.1%), Levophta (0.05% levocabastine), Emadine (0.05% emedastine), Tilavist (2% nedocromil), Allergodil (0.05% azelastine), Patanol (olopatadine), and Zaditen (0.025% ketotifen). Effects of preservative-free lodoxamide and ketotifen were also assessed and compared to those of the preserved formulations. A solution of 0.01% benzalkonium chloride (BAC), the most widely used preservative in topical eyedrops, was also tested. RESULTS: Zymosan-induced activation of complement (30+/-6%) was significantly lowered by preincubation of serum with unpreserved NAAGA (16.6+/-4%, p=0.0026) or benzalkonium-preserved nedocromil (20+/-2%, p=0.022). Preserved levocabastine, emedastine, olopatadine and ketotifen did not interfere with zymosan-induced complement activation, whereas preserved azelastine, lodoxamide and benzalkonium chloride significantly aggravated complement activation induced by zymosan. Similar results were obtained when complement activation was triggered by sand, common house dust, mascara, or by an allergenic extract of Dactylis glomerata pollen. In the absence of complement activator, none of the antiallergic eyedrops induced a significant change in CH50 titer, indicating that the deleterious pro-inflammatory effect of preserved azelastine and lodoxamide may occur only once complement activation has been initiated, i.e., on an inflamed ocular surface. CONCLUSION: Among the antiallergic eyedrops tested in this study, only Naabak and Tilavist were found to significantly inhibit complement activation triggered by particulate matters or pollen allergenic extract. Such an anticomplement activity confers these two molecules a potential in the therapeutic management of pollution-related pseudoallergic conjunctivitis.     

The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000

The editors of this Festschrift asked us to review the use of antibiotics for the treatment of bacterial conjunctivitis and keratitis over the past 25 years, a period coinciding with the life of the Castroviejo Corneal Society. We believe it is more appropriate to begin our review in the late 1960s. about the time that experimental and clinical studies and algorithms for the clinical care derived from these studies helped shape a more rigorous approach to therapy. Those years saw the introduction of antibiotics that were adapted for ophthalmic use, many of which are still being used today. We will give more weight to our review of keratitis than conjunctivitis.     

Contrast of the Effect of Alomide and Sodium Cromoglycate in the Treatment of Allergic Eye Diseases

Purpose: To observe the clinical effect of alomide and sodium cromoglycate eyedrops in the treatment of atopic conjunctivitis, vernal conjunctivitis and giant papillary conjunctivitis.Methods: Randomized control study was used. Alomide and sodium cromoglycate eyedrops used to treat two groups of patients for two weeks. The effects of the two groups were compared.Results: With respect of comprehensive therapeutic effect, the effectiveness rate was 83. 6% in alomide group, and 63. 3% in sodium cromoglycate group, which was not significantly different statistically. With respect of itching alleviation, alomide is more effective than sodium cromoglycate. No adverse effects were found in both groups. Conclusion: Our study suggests that alomide is a safe and effective drug in the treatment of allergic conjunctivitis. Eye Science 2000; 16: 214-216.     

Ocular Allergy

Ocular allergy is common, but it is often misdiagnosed and improperly treated. Most ocular allergy accompanies systemic or respiratory allergy, and it is rare to diagnose seasonal allergic conjunctivitis in the absence of systemic allergy. One exception is contact allergy, which is caused by eye medication, cosmetics, or other chemicals that come in contact with the delicate skin of the eyelids. Atopic keratoconjunctivitis and vernal conjunctivitis are uncommon, but severe forms of allergic conjunctivitis may be difficult to diagnose and to manage. In recent years, there have been several new antiallergic eyedrops that have either been approved for the management of allergic conjunctivitis or are being tested in clinical trials. In addition, modifications of steroid molecules have provided new and better treatment for ocular allergy and other types of ocular inflammation.     

Bioavailability of antibiotics

To be effective, an antibiotic must achieve therapeutic concentrations at the site of infection. This article is a review on the bioavailability of local and systemic antibiotics. Amongst topical antibiotics, fluoroquinolones and fusidic acid have the best intra-corneal and intra-cameral penetration. Chloramphenicol penetrates the anterior chamber but not always at therepeutic levels. Serum levels are low from topical administration, and haematological toxicity of chloramphenicol eyedrops is still not proven. Amongst systemic antibiotics, the molecules capable of penetrating the eye at therapeutic levels are fosfomycin, imipenem, some of third generation cephalosporins, fluoroquinolones and ureidopenicillins. Intra-ocular penetration of antibiotics is increased by infection, corneal epithelium abrasion, increasing dose frequency or delivery using a biomaterial reservoir (soft contact lenses or collagen schields). Antibiotic-antiinflammatory associations can make infected sites more accessible to antibiotics. The choice of a treatment must take in consideration molecules, dosing and route, and be adapted to the germ to kill and the infected site to treat.     

Fusidic acid prophylaxis before cataract surgery: patient self-administration

In a placebo-controlled, randomised, double-blind clinical trial, the authors evaluated the efficacy of patient-administered 1% fusidic acid viscous eye drops in clearing the commonest organisms causing pseudophakic endophthalmitis ( Staphylococcus epidermidis and aureus ) from the lids and conjunctivae of 79 patients before cataract surgery. The treatment group self-administered fusidic acid viscous eye drops four times daily for seven days before surgery; the placebo group received inert ophthalmic drops. Fellow eyes of both groups remained untreated as a natural control. Lower fornix and lid margin cultures were taken from both eyes before and after treatment. Before treatment, there was no statistical difference in organism counts between the groups. After treatment, eyes receiving fusidic acid were more likely to be free of clinically relevant Staphylococcus spp. than all pre-treatment eyes (for lids, P ≤ 0.001; conjunctivae, P = 0.02). A highly significant ( P <0.001) number of lid margins were rendered 'clinically clean' (i.e., 0–49 organisms/swab) by fusidic acid when compared with untreated eyes. Treatment also effectively ( P <0.05) reduced the numbers of bacteria isolated from conjunctivae. This study indicates that there is a highly significant reduction of Staphylococcus spp. (P≤0.001), non- Staphylococcus spp. (P≤ 0.001) and attainment of sterile eyes ( P≤ 0.001) at operation gained by patient self-administration of 1 % fusidic acid four times daily for seven days before surgery.     

Fusidic acid in acute conjunctivitis. Single-blind, randomized comparison of fusidic acid and chloramphenicol viscous eye drops

Fusidic acid 1% and chloramphenicol 0.5% eye drops were in a randomized, single-blind manner given as a one-week treatment to out-patients with acute, purulent conjunctivitis. A clinical success was recorded in 84% (102/121) of patients receiving fusidic acid and in 81% (104/129) of patients receiving chloramphenicol. More patients (14%) receiving chloramphenicol complained of trivial side effects such as stinging and local discomfort, compared with fusidic acid (5%). No serious side effects were recorded. It is concluded that fusidic acid dispensed in a carbomer eye vehicle represents an effective and well tolerated new topical eye preparation with the advantage of being administered twice daily.     

The differential diagnosis of red eye: a survey of medical practitioners from Eastern Europe and the Middle East

A survey amongst ophthalmologists and general medical practitioners from nine countries in Eastern Europe and the Middle East was conducted to estimate the percentage of patients presenting with a red eye and to examine differential diagnosis and treatment. Practitioners recorded brief details of every patient seen and detailed information concerning signs and symptoms, differential diagnosis and treatment for all patients presenting with a red eye during 20 consecutive days in the period between May and September 2004. Red eyes accounted for approximately 15% of consultations with ophthalmologists and almost 6% with general medical practitioners. Allergic conjunctivitis was the most common diagnosis (35%), followed by dry eye (25%) and bacterial conjunctivitis (24%). General medical practitioners were far more likely to prescribe a combination topical antibiotic and steroid preparation than ophthalmologists. This survey illustrates that red eye remains a very important problem for both ophthalmologists and general medical practitioners. Identification of dry eye as a common cause of red eye symptoms and more appropriate treatment of dry eye, allergic conjunctivitis and viral conjunctivitis are key messages to emerge.