特比萘芬治疗甲真菌病疗效观察

1999年5月至2001年5月,我们应用诺华制药公司生产的特比萘芬(terbinafine商品名为兰美抒)治疗65例甲真菌病,取得较满意疗效。     

特比萘芬治疗甲真菌病疗效观察

特比萘芬（商品名疗霉舒）是新一代高效、低毒、广谱抗真菌药物，其作用机制不同于唑类药物，是目前唯一具有杀菌作用的口服抗真菌药物。我们于１９９５年１０月起用该药对２６例资料完整的甲真菌病患者，进行临床治疗观察，疗效满意，现报告如下。临床资料男１２例，女１...     

特比萘芬治疗甲真菌病临床疗效观察

目的观察特比萘芬治疗甲真菌病的临床疗效。方法所有患者第1周均给予特比萘芬0.25 g口服,1次/d,第2周开始,隔日1次,每次0.25g,指甲真菌病患者共服7周,总量7 g,趾甲真菌病患者及指、趾同患真菌病患者共服11周,总量10.5 g,两组患者分别于服药后的第12周和第16周复诊观察近期疗效;服药后第24周复诊观察远期疗效。结果指甲真菌病患者近期治愈率为52.4%,趾甲真菌病及指、趾同患真菌病患者为35.2%,远期治愈率分别为85.7%和75.9%。结论特比萘芬治疗甲真菌病效果良好。     

特比萘芬治疗甲真菌病75例

笔者于2001年8月～2004年2月对75例甲真菌病患者采用特比萘芬（山东齐鲁制药厂生产）进行治疗，获得满意疗效，现报告如下：     

特比萘芬与伊曲康唑治疗甲真菌病疗效的Meta分析

目的系统评价特比萘芬与伊曲康唑治疗甲真菌病的有效性。方法计算机检索Cochrane图书馆、MEDLINE,Springer Datebase,CNKI,纳入所有比较特比萘芬与伊曲康唑治疗甲真菌病的随机对照试验(RCT)。由2名研究者共同独立提取资料并评估纳入研究质量。采用Cochrane协作网提供的RevMan4.2软件对试验数据进行统计分析。结果最终纳入6个RCT,其中4个特比萘芬250mg/d连续疗法与伊曲康唑200mg/d连续疗法、2个特比萘芬250mg/d连续疗法与伊曲康唑400mg/d冲击疗法治疗甲真菌病。Meta分析结果显示特比萘芬与伊曲康唑疗效的差异有统计学意义,合并后前者RR=1.25,95%CI(1.06～1.48),后者RR=2.02,95%CI(1.47～2.78)。均未报道特比萘芬和伊曲康唑引起的严重系统性不良反应。结论现有临床证据表明,特比萘芬治疗甲真菌病的疗效优于伊曲康唑。     

特比萘芬治疗甲真菌病的临床观察

我科从 1996年 1月起使用瑞士山德士药厂生产的口服抗真菌药特比萘芬 (商品名兰美舒 )治疗甲真菌病。我们对 2 5例资料完整的甲真菌病患者进行临床观察 ,疗效满意 ,现报告如下。临床资料 :2 5例均经临床及真菌学检查确诊。男性 18例 ,女性 7例 ,年龄平均 37 4岁 (2 4～ 6 5岁 )     

特比萘芬治疗甲真菌病的疗效观察

为了评价特比萘芬6周疗法治疗指甲真菌病、8周疗法治疗趾甲真菌病的疗效,我科于1999年5月至2000年5月采用诺华制药公司生产的特比萘芬对65例甲真菌病进行了治疗和2年的随访,得到了较为满意的结果,现报道如下。     

特比萘芬治疗甲真菌病57例临床观察

目的观察特比萘芬治疗甲真菌病的疗效及安全性。方法治疗组口服特比萘芬片250 mg,1次/d,单纯指甲受累者连用9周,单纯趾甲受累或伴有指甲受累者连用12周;对照组采用30%冰醋酸外涂,2次/d,连用3个月。分别于停药时、第6,9个月时进行临床和真菌学评价。结果治疗组停药时、第6,9个月时,治愈率分别为4 9.1 2%,80.70%和89.47%;有效率分别为80.70%,91.22%和89.47%;真菌学治愈率分别为43.86%,94.74%和94.74%。治疗后各阶段的临床治愈率、有效率及真菌学治愈率均明显高于同时段对照组(P<0.01)。治疗组有3例出现胃肠道不适,1例出现一过性ALT升高,不影响治疗。结论特比萘芬治疗甲真菌病近、远期疗效好,临床和真菌学治愈率高,不良反应少,安全性好。     

特比萘芬治疗甲真菌病120例

为进一步观察特比萘芬(兰美抒)连续疗法治疗甲真菌病的疗效和安全性,特别是远期疗效,2001年2月至2002年12月我们在门诊治疗观察了120例甲真菌病患者,现将结果报道如下。     

Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis

BACKGROUND: Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. OBJECTIVES: A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. METHODS: We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). RESULTS: There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 +/- 6% (n = 2 studies, 79 patients) to 76 +/- 3% (n = 18 studies, 993 patients) (P = 0.68); itraconazole pulse, 75 +/- 10% (n = 1 study, 20 patients) to 63 +/- 7% (n = 6 studies, 318 patients) (P = 0.25); itraconazole continuous, 63 +/- 5% (n = 1 study, 84 patients) to 59 +/- 5% (n = 7 studies, 1131 patients) (P = 0.47); fluconazole, 53 +/- 6% (n = 1 study, 72 patients) to 48 +/- 5% (n = 3 studies, 131 patients) (P = 0.50); and griseofulvin, 55 +/- 8% (n = 2 studies, 109 patients) to 60 +/- 6% (n = 3 studies, 167 patients) (P = 0.41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 +/- 3% (n = 18 studies, 993 patients) vs. 83 +/- 12% (n = 2 studies, 391 patients) (P = 0.0028); itraconazole pulse, 63 +/- 7% (n = 6 studies, 318 patients) vs. 84 +/- 9% (n = 3 studies, 194 patients) (P = 0.0001); and fluconazole, 48 +/- 5% (n = 3 studies, 131 patients) vs. 79 +/- 3% (n = 3 studies, 208 patients) (P = 0.0001). CONCLUSIONS: The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates.     

Continuous and intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison

This multicentre, double-blind, randomized study compared the pharmacokinetics of itraconazole given at 200 mg once daily for 3 months and intermittently at 200 mg twice daily for 1 week per month followed by a 3-week drug-free period for 3 months in the treatment of onychomycosis. Patients were followed for 9 months after treatment. Itraconazole and hydroxy-itraconazole plasma concentrations and itraconazole nail tip concentrations were determined at regular intervals. With intermittent therapy (n = 64), increases of consistent magnitude were seen in the mean itraconazole and hydroxy-itraconazole plasma concentrations at the end of each 1-week treatment phase; values returned towards baseline during each subsequent 3-week drug-free period. The mean concentration of itraconazole in fingernail tips increased steadily from week 4, reached a maximum value at week 24 (213 ng/g), declined sharply between weeks 24 and 36 and returned to baseline by week 48; the mean concentration profile was similar for toenail tips (maximum value 305 ng/g at week 24) but decreased at a slower rate. With continuous therapy (n = 65), steady-state mean plasma concentrations of itraconazole and hydroxy-itraconazole were obtained within 4-5 weeks of the start of treatment and remained reasonably constant between weeks 4 and 12. The mean concentration of itraconazole in fingernail tips reached a maximum value at week 12 (524 ng/g) and returned towards baseline by week 48; in contrast, the maximum mean concentration of itraconazole in toenail tips was 698 ng/g at week 36 and did not return to baseline by week 48. No clear relationship was observed between response to treatment and concentration of itraconazole or hydroxy-itraconazole in plasma or itraconazole in nails, suggesting that concentrations exceeded therapeutic levels. In conclusion, intermittent therapy resulted in higher maximum itraconazole plasma concentrations but lower total drug exposure, and hence lower itraconazole nail concentrations, than continuous therapy. However, the intermittent schedule was not associated with a lower cure rate, which indicates that itraconazole nail concentrations remained within the therapeutic range.     

Iontophoretic delivery of terbinafine in onychomycosis: a preliminary study

Background  Onychomycosis is a common disease; topical treatment is usually poorly effective, while systemic treatment is more effective but may be associated with side-effects. Iontophoretic drug delivery may improve drug penetration through the nail and lead to better therapeutic results.
Objectives  To evaluate the efficacy, safety and tolerability of topical treatments with terbinafine HCl delivered with or without an iontophoretic patch in patients with onychomycosis of the toenails.
Methods  Patients enrolled into the study were divided randomly into two groups. Group A was treated with terbinafine and an iontophoretic patch (at a constant current density of 100 μA cm⁻²). Group B was treated with terbinafine without iontophoresis. Treatment was overnight wear, every day, 5 days per week, for 4 weeks. Follow-up period was 8 weeks from the end of treatment.
Results  A significant clinical response was recorded in patients of group A (active group). The percentage of patients having healthy toenail growth of more than 1·5 mm at the end of treatment was 40% compared with 11% in patients treated with terbinafine without current (passive group). The percentage of patients having fungal elements (KOH) in nail specimens decreased significantly at 8 weeks following the completion of treatment: 16% in the active group vs. 53% in the passive group. Patients in the active group reported a tingling sensation that is expected when using an iontophoretic drug delivery treatment.
Conclusions  The delivery of terbinafine under an electrical current of 100 μA cm⁻² appears to be efficacious and safe and is well tolerated for the treatment of nail onychomycosis.     

Update: medical treatment of onychomycosis

The diagnosis of onychomycosis should be made clinically and mycologically: clinically, by one of seven subtypes of onychomycosis, and mycologically, by evidence of dermatophytes or verified presence of molds and/or yeasts. Dermatophytes are usually considered as pathogens, whereas non‐dermatophyte molds and yeasts are saprophytes. Basic anamnesis and close inspection should be performed to eliminate combined diseases (e.g., onychomycosis and trauma). The gold standard treatment for onychomycosis is basically systemic. Combination with topical agents, such as nail lacquer and/or chemical nail avulsion, produces better results than systemic treatment alone. Topical treatment as monotherapy is not efficient, excluding minor cases. Terbinafine is superior to itraconazole for dermatophyte onychomycosis. Evaluation of the outcome of clinical cure, mycological cure and total cure should be based on the well‐defined worldwide criteria; otherwise, comparison of results is impossible due to lack of uniformity in different studies. In case of treatment failure, the reasons for each failure should be carefully considered.     

Itraconazole pulse therapy for the treatment of Candida onychomycosis

In this open label, multicentre trial, 44 patients with clinical and mycological evidence of Candida onychomycosis were treated with itraconazole pulse therapy. Onychomycosis of the toes alone and concomitant disease involving the fingers and toes was treated with three pulses, and onychomycosis of the fingers alone with two pulses. Final evaluation for patients with finger and toe onychomycosis was at 6-9 months and 9-12 months, respectively. There were 29 patients with toe onychomycosis (C. albicans, 27; C. glabrata, one; Candida species, one), 12 patients with finger onychomycosis (C. albicans, two; C. glabrata, one) and three patients had combined toe and finger onychomycosis (C. albicans, two; C. guillermondii, one). In the patients with toe onychomycosis mycological cure was observed in 29 of 32 patients (90.6%). There was complete cure [mycological cure (negative culture and KOH at endpoint evaluation) with clinical cure] or marked improvement (mycological cure with 75% or greater decrease in area of involvement of target nail compared with pretherapy) in 24 of 32 patients (75.0%). All 12 patients with finger onychomycosis alone due to Candida species achieved a mycological cure (100%). In this group of patients complete cure or marked improvement was observed in 11 of 12 patients (91.7%). Itraconazole pulse therapy was well tolerated and no serious adverse events were reported in the patients treated with this triazole. In conclusion, itraconazole pulse therapy is an effective and safe treatment for both finger and toe onychomycosis associated with Candida.     

甲真菌病的治疗与思考

笔者40余年经历了化学剥甲治疗甲真菌病，各种口服抗真菌药治疗甲真菌病，各种外用抗真菌药治疗甲真菌病的临床实践。于2003年出版了“甲真菌病诊治彩色图谱”，把个人肤浅的体会介绍给同道们可能会有帮助。一、甲真菌病流行病学：国外平均为9．1％，国内平均为15％，香港居民趾甲真菌病为17％-21％。它占浅部真菌病的30％，占整个足病的50％。二、甲真菌病对患者严重影响生活质量，甲真菌病是致病真菌的贮库对患者本人，对家庭和对社会都有一定的传播性。三、口服酮康唑治疗甲真菌病发生致命性中毒性肝炎已死亡不少患者，希望不再发生此类医源性死亡事件。四、对甲真菌病患者开出口服抗真菌药处方之前必需三思而后行。1、治疗之前甲真菌病的诊断确切无疑，2．处方前必须做好患者的思想工作，让患者认识到服药时间较长，费用较贵，而且可能有一定的不良反应，3．对患有系统性疾病的患者用药要谨慎，尽可能地避免发生药物相互作用。五、甲真菌病的诊断要提高到真菌学水平。1，真菌学确诊可以避免误诊，2．明确致病性真菌可以有的放矢，选择更有效的抗真菌药，3．甲真菌病进行真菌学检查可以发现新的致病菌，可以观察到致病性真菌的变迁。六、甲真菌病治疗失败、复发和再感染，治疗失败有许多原因，复发的关键问题是药量不足。七、对甲真菌病治疗应采取首诊负责制，在治愈之后至少要再随访一年。八、甲真菌病治疗学的发展方向：甲真菌病根据病情的轻重可以采取化学剥甲治疗，外用抗真菌药治疗和口服抗真菌药治疗。口服抗真菌药的治愈率也只有60-75％，失败率占25％-40％。甲真菌病联合疗法可以起到协同增效作用，起效更快，减少口服药物总量，提高治愈率，降低失败率与复发率，提高患者的耐受性和顺从性。这是甲真菌病今后治疗的新方向。目前对5％阿莫罗芬甲涂剂与口服伊曲康唑或特比茶芬联合治疗已取得成功的经验，把治疗水平更提高一步。     

Toenail onychomycosis: current and future treatment options

Onychomycosis is a common disease affecting as much as 8% of the general population. Treatment of onychomycosis is challenging, complicated by low cure rates and relatively high relapse rates. This paper reviews the efficacy of current oral, topical, and surgical treatment options. Currently, the treatment of choice for toenail onychomycosis is oral terbinafine because of its high efficacy, low relapse rates, and cost-effectiveness. Oral itraconazole or fluconazole could be considered for infections caused by Candida. Topical therapies may be a useful adjunct to these systemic therapies, but are less effective when used alone. More research is needed to determine the best measures for preventing reinfection.     

Prognostic factors for cure following treatment of onychomycosis

Objective To examine if host baseline factors and week 24 mycology results are associated with mycological and clinical cure in patients with onychomycosis treated with oral terbinafine. Design Open pilot study to determine prognostic factors in the treatment of onychomycosis. Setting Outpatient dermatology clinic. Patients A total of 199 patients from the Icelandic arm of a trial comparing continuous terbinafine with intermittent terbinafine in onychomycosis were recruited for additional observation. Main outcome measures Mycological, clinical and complete cure of the target toenail 72 weeks after treatment was initiated. Results Patients with matrix involvement or slow nail growth were less likely to reach mycological, clinical and complete cure. Lateral involvement affected complete and mycological cure rates negatively. Patients with a dermatophytoma were less likely to reach mycological cure. Patients with a history of prior infection, men and older patients were less likely to reach clinical cure. Positive culture at 24 weeks affected mycological and clinical cure at 72 weeks negatively. Limitations Only patients treated with terbinafine were considered. Conclusions Several host‐related factors at baseline and positive culture at 24 weeks had negative effects on cure of onychomycosis 72 weeks after treatment was initiated. This finding merits a large study on prognostic outcome factors in onychomycosis.