Therapeutic Options for the Treatment of Tinea Capitis Caused by Trichophyton Species: Griseofulvin Versus the New Oral Antifungal Agents, Terbinafine, Itraconazole, and Fluconazole

Tinea capitis is a relatively common fungal infection of childhood. Griseofulvin has been the mainstay of management. However, newer oral antifungal agents are being used more frequently. A multicenter, prospective, randomized, single-blinded, non-industry-sponsored study was conducted in centers in Canada and South Africa to determine the relative efficacy and safety of griseofulvin, terbinafine, itraconazole, and fluconazole in the treatment of tinea capitis caused by Trichophyton species. The regimens for treating tinea capitis were griseofulvin microsize 20 mg/kg/day x 6 weeks, terbinafine [> 40 kg, one 250 mg tablet; 20-40 kg, 125 mg (half of a 250 mg tablet); < 20 kg, 62.5 mg (one-quarter of a 250 mg tablet)] x 2-3 weeks, itraconazole 5 mg/kg/day x 2-3 weeks, and fluconazole 6 mg/kg/day x 2-3 weeks. Patients were asked to return at weeks 4, 8, and 12 from the start of the study. Griseofulvin was administered for 6 weeks and the final evaluation was at week 12. Terbinafine, itraconazole, and fluconazole were administered for 2 weeks and the patient evaluated 4 weeks from the start of therapy. At this time, if clinically indicated, one extra week of therapy was given. There were 200 patients randomized to four treatment groups (50 in each group). At the final evaluation at week 12, the number of evaluable patients were griseofulvin, 46; terbinafine, 48; itraconazole, 46; and fluconazole, 46. Patients who discontinued therapy or were lost to follow-up were griseofulvin, 1/3; itraconazole, 0/4; terbinafine, 0/4; and fluconazole, 0/4. The causative organisms were Trichophyton tonsurans and T. violaceum species. Patients were regarded as effectively treated at week 12 if there was mycologic cure and either clinical cure or only a few residual symptoms. Effective treatment was recorded in, intention to treat, griseofulvin (46 of 50, 92.0%), terbinafine (47 of 50, 94.0%), itraconazole (43 of 50, 86.0%), and fluconazole (42 of 50, 84.0%) (p=0.33). Adverse effects were reported only in the griseofulvin group (gastrointestinal effects in six patients). Discontinuation from therapy due to adverse effects occurred only in the griseofulvin group (nausea in one patient). For the treatment of tinea capitis caused by the Trichophyton species, in this study, griseofulvin given for 6 weeks is similar in efficacy to terbinafine, itraconazole, and fluconazole given for 2-3 weeks. Each of the agents has a favorable adverse-effects profile.     

Single-blind, randomized, prospective study on terbinafine and itraconazole for treatment of dermatophyte toenail onychomycosis in the elderly

BACKGROUND: The 2 most common agents used to treat dermatophyte onychomycosis of the toe are terbinafine (continuous) and itraconazole (pulse). Although comparative studies have been performed evaluating the efficacy of these 2 agents in adults, no such studies have been reported specifically in the elderly subset. OBJECTIVE: This prospective, randomized, single-blind, non--industry-sponsored, comparative study evaluated the efficacy and safety of terbinafine (continuous) and itraconazole (pulse) therapies in the treatment of dermatophyte onychomycosis of the toe in the elderly population. METHODS: Elderly patients (> or =60 years old) with dermatophyte onychomycosis of at least 1 great toe were randomly assigned to receive either terbinafine 250 mg/day for 12 weeks or itraconazole (pulse) 200 mg twice a day for 1 week, given for 3 pulses. At month 6 from the start of therapy, if there was less than 50% reduction in the affected nail plate area compared with baseline, or if there was less than 3 mm outgrowth of unaffected nail plate as measured in midline, then patients who had been administered terbinafine (continuous) therapy were given an extra 4 weeks of the drug (total of 16 weeks of therapy), and those who had received itraconazole (pulse) therapy were given an extra pulse (fourth pulse). Patients were evaluated at 1.5, 3, 6, 12, and 18 months from the start of therapy. The efficacy measures included mycologic cure rate and clinical efficacy (mycologic cure plus clinical cure or clinical improvement so that 10% or less of nail plate was clinically involved). RESULTS: There were 101 elderly patients enrolled in the study with 50 and 51 patients receiving terbinafine and itraconazole, respectively. The terbinafine group consisted of 28 men and 22 women, age (mean +/- standard error [SE]) 68.0 +/- 0.9 years, duration of onychomycosis (mean +/- SE) 18.2 +/- 1.4 years, number of nails involved (mean +/- SE) 5.5 +/- 0.5, and percent baseline nail plate area involved (mean +/- SE) 67.5% +/- 4.2%. The corresponding figures for the itraconazole (pulse) group were 24 men and 27 women, age (mean +/- SE) 68.8 +/- 0.8 years, duration of onychomycosis (mean +/- SE) 16.1 +/- 1.7 years, number of nails involved (mean +/- SE) 6.0 +/- 0.7, and percent baseline nail plate area involved (mean +/- SE) 74.9% +/- 3.8%, respectively, with no significant difference between the groups. At month 6, the number of patients that required an extra 4 weeks of terbinafine in the allylamine group or an extra itraconazole pulse in the triazole group was 13 of 50 and 23 of 51, respectively. The mycologic cure rate and clinical efficacy at 18 months from the start of therapy for the terbinafine group were 64.0% and 62.0%, respectively. The corresponding figures for the itraconazole (pulse) group were 62.7% and 60.8%, respectively, with no significant difference between the 2 groups. There were no dropouts during therapy. For both groups the drug appeared safe with no significant adverse events (AEs) or clinically significant laboratory abnormalities. All the AEs were mild and transient. There was high compliance with both regimens. CONCLUSIONS: In the elderly, for the treatment of dermatophyte toe onychomycosis, both terbinafine (continuous) and itraconazole (pulse) therapies are effective, safe, and associated with high compliance.     

Efficacy of itraconazole, terbinafine, fluconazole, griseofulvin and ketoconazole in the treatment of Scopulariopsis brevicaulis causing onychomycosis of the toes

BACKGROUND: Scopulariopsis brevicaulis is a common non-dermatophyte mould that can cause onychomycosis. OBJECTIVE: To evaluate the efficacy and safety of the oral antifungal agents griseofulvin, ketoconazole, itraconazole, fluconazole and terbinafine in the treatment of S. brevicaulis. PATIENTS AND METHODS: In a prospective, comparative, parallel-group, single-blinded, randomized, non-industry-sponsored study, patients with toe onychomycosis caused by S. brevicaulis sp. were randomized and treated with one of 5 oral antifungal agents, i.e. griseofulvin, ketoconazole, itraconazole (pulse), fluconazole or terbinafine. The treatment regimens were: griseofulvin 600 mg twice daily for 12 months, ketoconazole 200 mg daily for 4 months, itraconazole pulse therapy given for 3 pulses, with each pulse consisting of 200 mg twice daily for 1 week with 3 weeks off between successive pulses, terbinafine 250 mg daily for 12 weeks and fluconazole 150 mg daily for 12 weeks. RESULTS: There were 59 patients (48 males, 11 females, mean age 35.6 years, range 25-53 years). All patients had clinical evidence of distal and lateral onychomycosis, with moderate to severe disease of the target nail. Between the treatment groups there was no significant difference in the mean age of the patients or the mean area of involvement with onychomycosis at baseline. The efficacy parameters were clinical cure (CC) and mycological cure (MC). At month 12 after the start of treatment, the response was: griseofulvin, CC 3/11, MC 0/11, CC + MC 0/11; ketoconazole, CC 10/12, MC 8/12, CC + MC 8/12; itraconazole, CC 12/12, MC 12/12, CC + MC 12/12; terbinafine, CC 12/12, MC 11/12, CC + MC 11/12, and fluconazole, CC 8/12, MC 8/12, CC + MC 8/12. Adverse effects consisted of: griseofulvin, gastro-intestinal symptoms, allergic reaction, photodermatitis, hepatic and renal dysfunction in 11 patients with discontinuation of treatment in 3 patients; ketoconazole, hepatic dysfunction but no symptomatic changes in 2 patients; itraconazole, nausea and vomiting in 2 patients; terbinafine, taste disturbance in 2 patients, nausea in 3 patients, and fluconazole, severe gastro-intestinal events in 5 patients. None of the patients receiving ketoconazole, itraconazole, terbinafine or fluconazole discontinued treatment. CONCLUSIONS: Itraconazole and terbinafine demonstrate efficacy against some cases of S. brevicaulis toe onychomycosis. These agents also appear to be safe in the course of therapy for toe onychomycosis. Griseofulvin is ineffective against toe onychomycosis caused by S. brevicaulis. Ketoconazole is not recommended for toe onychomycosis given its potential for adverse effects, particularly with the availability of the newer antifungal agents.     

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.     

Terbinafine: a review of its use in onychomycosis in adults

Terbinafine, an orally and topically active antimycotic agent, inhibits the biosynthesis of the principal sterol in fungi, ergosterol, at the level of squalene epoxidase. Squalene epoxidase inhibition results in ergosterol-depleted fungal cell membranes (fungistatic effect) and the toxic accumulation of intracellular squalene (fungicidal effect). Terbinafine has demonstrated excellent fungicidal activity against the dermatophytes and variable activity against yeasts and non-dermatophyte molds in vitro. Following oral administration, terbinafine is rapidly absorbed and widely distributed to body tissues including the poorly perfused nail matrix. Nail terbinafine concentrations are detected within 1 week after starting therapy and persist for at least 30 weeks after the completion of treatment. Randomized, double-blind trials showed oral terbinafine 250 mg/day for 12 or 16 weeks was more efficacious than itraconazole, fluconazole and griseofulvin in dermatophyte onychomycosis of the toenails. In particular, at 72 weeks' follow-up, the multicenter, multinational, L.I.ON. (Lamisil vs Itraconazole in ONychomycosis) study found that mycologic cure rates (76 vs 38% of patients after 12 weeks' treatment; 81 vs 49% of recipients after 16 weeks' therapy) and complete cure rates were approximately twice as high after terbinafine treatment than after itraconazole (3 or 4 cycles of 400 mg/day for 1 week repeated every 4 weeks) in patients with toenail mycosis. Furthermore, the L.I.ON. Icelandic Extension study demonstrated that terbinafine was more clinically effective than intermittent itraconazole to a statistically significant extent at 5-year follow-up. Terbinafine produced a superior complete cure rate (35 vs 14%), mycologic cure rate (46 vs 13%) and clinical cure rate (42 vs 18%) to that of itraconazole. The mycologic and clinical relapse rates were 23% and 21% in the terbinafine group, respectively, compared with 53% and 48% in the itraconazole group. In comparative clinical trials, oral terbinafine had a better tolerability profile than griseofulvin and a comparable profile to that of itraconazole or fluconazole. Post marketing surveillance confirmed terbinafine's good tolerability profile. Adverse events were experienced by 10.5% of terbinafine recipients, with gastrointestinal complaints being the most common. Unlike the azoles, terbinafine has a low potential for drug-drug interactions. Most pharmacoeconomic evaluations have shown that the greater clinical effectiveness of oral terbinafine in dermatophyte onychomycosis translates into a cost-effectiveness ratio superior to that of itraconazole, fluconazole and griseofulvin. CONCLUSION: Oral terbinafine has demonstrated greater effectiveness than itraconazole, fluconazole and griseofulvin in randomized trials involving patients with onychomycosis caused by dermatophytes. The drug is generally well tolerated and has a low potential for drug interactions. Therefore, terbinafine is the treatment of choice for dermatophyte onychomycosis.     

Treatment of tinea imbricata: a randomized clinical trial using griseofulvin, terbinafine, itraconazole and fluconazole

BACKGROUND: Griseofulvin has been the mainstay of treatment for tinea imbricata (TI) for decades; however, there have been few reports of efficacy of newer antifungals in the treatment of this condition. Many patients with TI have several obstacles to treatment due to their remote geographical locations and the primitive nature of their societies. OBJECTIVES: The aim of this study was to compare the efficacy of itraconazole, terbinafine and fluconazole with that of griseofulvin after 4 weeks of therapy. METHODS: Patients aged 12-76 years with the clinical diagnosis of TI were randomly assigned to one of four treatment groups: griseofulvin 500 mg twice daily for 4 weeks, terbinafine 250 mg daily for 4 weeks, itraconazole 200 mg twice daily for 1 week or fluconazole 200 mg once weekly for 4 weeks. Disease activity was monitored weekly. Laboratory measurements included monitoring complete blood count and liver function enzymes. Fifty-nine patients were included in the efficacy analysis: 13 in the fluconazole group, 15 in the griseofulvin group, 12 in the terbinafine group and 19 in the itraconazole group. RESULTS: Significant remission was achieved in the terbinafine and griseofulvin groups, lasting up to 8 weeks after cessation of therapy. The fluconazole group experienced no significant remission, and remission was of short duration in the itraconazole group. No adverse events were reported, and non-compliance with medications or follow-up was the only reason for removal from the study. CONCLUSIONS: Griseofulvin and terbinafine are effective in the treatment of TI. The decision of whether to treat at all and which medication to choose depends greatly on the extent of involvement, the social situation, and the availability of resources such as laboratory testing and follow-up.     

Onychomycosis: a new emerging infectious disease in childhood population and adolescents. Report on treatment experience with terbinafine and itraconazole in 36 patients

Background Onychomycosis is a rare disease in children with an estimated prevalence ranging from 0% to 2.6%. Thus far, only limited experience with itraconazole and terbinafine treatment in children with onychomycosis is available in the literature. Aim of the study Evaluation of treatment experience with itraconazole or terbinafine in childhood onychomycosis. Subjects Thirty‐six children and adolescents (aged 4–17 years, 18 males and 18 females) with clinical and mycologically proven onychomycosis were enrolled in the present study. Methods and outcome In 27 of 36 patients, the causative agent (Trichophyton rubrum in 26 cases and Trichophyton interdigitale in one patient) could be identified by means of cultivation. Nineteen patients were treated with itraconazole 200 mg once daily for 12 weeks, and 17 patients were treated with terbinafine for 12 weeks in a dosage according to their body weight, respectively. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported.Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. Conclusion To our experience, a mycological and clinical cure appears in children in a shorter time after treatment discontinuation (average 2–5 months) compared with adults. Itraconazole and terbinafine seem to be safe and effective in childhood onychomycosis; therefore, these antifungals seem to be potential alternatives to griseofulvin.     

口服特比萘芬与伊曲康唑治疗儿童头癣的疗效比较

目的比较口服特比萘芬与伊曲康唑治疗儿童头癣的疗效。方法 2021年1-12月北京儿童医院皮肤科门诊头癣患儿53例, 采用随机数字表法分为特比萘芬治疗组(体重< 20 kg, 剂量62.5 mg/d;体重20 ～ 40 kg, 剂量125 mg/d;体重> 40 kg, 剂量250 mg/d)和伊曲康唑治疗组(3 ～ 5 mg·kg-1·d-1)。使用SPSS23.0软件进行统计分析, 组间计数资料比较采用χ2检验或Fisher确切概率法。结果特比萘芬治疗组27例(白癣17例、脓癣10例), 治愈14例(51.85%), 其中白癣5例, 脓癣9例。伊曲康唑治疗组26例(白癣17例、脓癣9例), 治愈25例(96.15%), 其中白癣16例, 脓癣9例。伊曲康唑组的疗效显著高于特比萘芬组, χ2 = 13.37, P < 0.001。结论伊曲康唑治疗儿童白癣的效果优于特比萘芬, 但两药治疗儿童脓癣的疗效相当。     

Long-term effectiveness of treatment with terbinafine vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study

OBJECTIVE: To examine long-term cure and relapse rates after treatment with continuous terbinafine and intermittent itraconazole in onychomycosis. DESIGN: Long-term prospective follow-up study. SETTING: Three centers in Iceland. SUBJECTS: The study population comprised 151 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte toenail onychomycosis. INTERVENTIONS: In a double-blind, double-dummy study, patients were randomized to receive either terbinafine (250 mg/d) for 12 or 16 weeks or itraconazole (400 mg/d) for 1 week in every 4 for 12 or 16 weeks (first intervention). Patients who did not achieve clinical cure at month 18 or experienced relapse or reinfection were offered an additional course of terbinafine (second intervention). MAIN OUTCOME MEASURES: The primary efficacy criterion was mycological cure, defined as negative results on microscopy and culture at the end of follow-up and no requirement of second intervention treatment. Secondary efficacy criteria included clinical cure without second intervention treatment and mycological and clinical relapse rates. RESULTS: Median duration of follow-up was 54 months. At the end of the study, mycological cure without second intervention treatment was found in 34 (46%) of the 74 terbinafine-treated subjects and 10 (13%) of the 77 itraconazole-treated subjects (P<.001). Mycological and clinical relapse rates were significantly higher in itraconazole vs terbinafine-treated patients (53% vs 23% and 48% vs 21%, respectively). Of the 72 patients who received subsequent terbinafine treatment, 63 (88%) achieved mycological cure and 55 (76%) achieved clinical cure. CONCLUSION: In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole.     

特比萘芬和伊曲康唑治疗原发性皮肤曲霉病2例疗效观察

分别应用特比萘芬、伊曲康唑治疗2例皮肤曲霉病,并对其治疗前后真菌学和组织病理改变进行对比观察。例1,男,38岁,躯干部出现多发性坏死性溃疡2个月。通过真菌学、组织病理和扫描电镜观察确诊为黄曲霉所致原发性皮肤曲霉病。口服特比萘芬,500mg/d,治疗4周后治愈。例2,女,28岁,双手背、左跟腱部发生数个结节及坏死性溃疡8个月。实验室检查方法和诊断基本同例1。给予伊曲康唑口服,400mg/d,5周后显著好转,将剂量减至200mg/d,维持治疗至3个月后临床痊愈。例1、例2于治疗后做真菌分离培养均未见生长,组织病理复查病灶亦无真菌。     

In vitro antifungal susceptibility testing of fungi in patients with onychomycosis

Onychomycosis is the most common nail disorder. To examine in vitro antifungal susceptibility of fungi among onychomycosis patients. The study included 68 patients with onychomycosis. Nail specimens were cultured on Sabouraud dextrose agar and Dermasel agar base‐media. Isolated fungi were subjected to antifungal susceptibility tests against terbinafine, itraconazole, fluconazole, and griseofulvin. Candida species (Candida spp.) were detected in 32.4% of the cases of candidal onychomycosis (n = 37), 23.5% of the cases of distal and lateral subungual onychomycosis (n = 17), and 21.4% of the cases of total dystrophic onychomycosis (n = 14). Candida spp. were sensitive to fluconazole in 73.5%, itraconazole in 58.8%, and terbinafine in 5.9% of the cases. Aspergillus spp. were sensitive to itraconazole in all cases, and terbinafine in 87.5% of cases. Penicillium spp. were sensitive to itraconazole and terbinafine in 88.9% and 77.8% of cases, respectively. Trichophyton spp. were sensitive to terbinafine and resistant to itraconazole. Microsporum spp. were sensitive to itraconazole and resistance to terbinafine. All isolated fungi were resistant to griseofulvin. An increasing proportion of Candida spp. was observed among patients with different clinical varieties of onychomycosis. Candida spp. were highly sensitive to fluconazole and a lesser extent to itraconazole.     

Drug interactions of the newer oral antifungal agents

The newer oral antifungal agents, such as fluconazole, itraconazole and terbinafine, are generally both effective and well tolerated in the management of widespread or resistant dermatomycoses such as onychomycosis. However, these agents differ markedly in their potential to cause clinically significant drug interactions. Triazoles such as fluconazole and itraconazole have been responsible for a greater number of clinically significant drug interactions than terbinafine. For example, itraconazole, and to a lesser extent fluconazole (in high doses) are inhibitors of CYP3A4. Therefore certain agents that are substrates of this enzyme, such as some of the new generation of H₁-antihistamines, several HMG-CoA reductase inhibitors and certain benzodiazepines, are contraindicated. Other drugs like cyclosporine and quinidine need careful monitoring if administered concurrently with these triazoles. In contrast, there are no drug–drug contraindications with terbinafine. Indeed, in a postmarketing surveillance study, in which 42.8% of the 25,884 participating patients were taking a variety of concomitant therapies, no new drug–drug interactions were revealed. Physicians should be aware of the potential for interaction of the medications that they prescribe, in order to prevent or reduce the burden of adverse events. Terbinafine may be the most rational choice of oral antifungal agent in patients receiving concomitant medications that may adversely affect or be affected by either fluconazole or itraconazole.     

Antifungal susceptibilities of dermatophytic agents isolated from clinical specimens

The aim of this study was to investigate the susceptibility to four antifungal agents: ketoconazole, terbinafine, itraconazole and fluconazole, of the different species of dermatophyte strains isolated from clinical specimens. A total of 128 specimens were collected from toe nail, foot, inguinal region, trunk, hands and head. The dermatophytes tested included Trichophyton rubrum 108 (84.4%), Trichophyton mentagrophytes 11 (8.6%), Epidermophyton floccosum 5 (3.9%), Microsporum canis 2 (1.5%) and Trichophyton tonsurans 2 (1.5%). The mean minimum inhibitory concentrations (MIC) for the five species of dermatophytes ranged between 0.09-1.12 microg/mL for ketoconazole, 0.04-0.27 microg/mL for terbinafine, 0.08-0.43 microg/mL for itraconazole and 16.18-24.0 microg/mL for fluconazole. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different systemic antifungals, which in turn may clarify the reasons for the lack of clinical response or serve as an effective therapy for patients with chronic infection.     

伊曲康唑、氟康唑与特比萘芬联合治疗肺隐球菌病1例

采用伊曲康唑、氟康唑与特比萘芬联合治疗1例肺隐球菌病。患者男,48岁。发热、咳嗽、右肺部出现大片阴影27d。经皮肺穿刺活检,确诊为肺隐球菌病。给予氟康唑150mg／a、特比萘芬250mg／a口服治疗,1个月后复查胸部X线片及CT,肺部病变明显好转,但随后恢复较慢,改用伊曲康唑200mg／a联合特比萘芬250mg／d口服治疗3个月后,肺部阴影完全消失。     

四种抗真菌药物治疗甲癣疗效比较的文献系统复习

目的比较特比萘芬与伊曲康唑、氟康唑、灰黄霉素治疗甲癣疗效的差异。方法检索Medline文献数据库,查找所有比较特比萘芬与伊曲康唑、氟康唑、灰黄霉素治疗甲癣的双盲随机对照试验的文献,找出这4种药物治疗甲癣的真菌学治愈率并对其进行汇总,得出合并后真菌学治愈率的比值比(OR)及其95%可信区间(CI)。结果①有6篇比较特比萘芬与伊曲康唑、1篇特比萘芬与氟康唑、2篇特比萘芬与灰黄霉素治疗甲癣的双盲随机对照试验文献被纳入。②特比萘芬250mg/d连续疗法优于伊曲康唑400mg/d冲击疗法[OR=5.01,95%CI(3.42～7.33)]和伊曲康唑200mg/d连续疗法[OR=2.58,95%CI(1.91～3.49)]。特比萘芬的疗效亦优于氟康唑(P<0.001)和灰黄霉素[OR=3.46,95%CI(1.89～6.31)]。结论特比萘芬治疗甲癣的疗效优于伊曲康唑、氟康唑和灰黄霉素。     

微量稀释法检测申克孢子丝菌酵母相体外抗真菌药物敏感性

目的用液基微量稀释法观察双相真菌申克孢子丝菌酵母相体外抗真菌药物敏感性。方法将54株申克孢子丝菌临床株于脑心浸液琼脂培养基连续传代获得酵母相,参考美国临床实验室标准化委员会(CLSI)的微量稀释法M27-A2检测菌株酵母相对碘化钾、氟康唑、伊曲康唑和特比萘芬的体外敏感性,并观察碘化钾对伊曲康唑和特比萘芬体外抑菌作用的影响。质控株为克柔念珠菌ATCC6258。结果碘化钾体外无抑菌作用;氟康唑最小抑菌浓度(MIC)几何均数大于64μg/mL;伊曲康唑和特比萘芬MIC几何均数分别为0.98μg/mL和0.17μg/mL。伊曲康唑及特比萘芬的MIC值分别高于伊曲康唑+碘化钾及特比萘芬+碘化钾(P均<0.05)。来源皮肤固定型的菌株与来源皮肤淋巴管型菌株相比MIC值差异无统计学意义(P>0.05)。结论改良的M27-A2方法适用于检测申克孢子丝菌酵母相体外敏感性;酵母相时碘化钾对伊曲康唑、特比萘芬体外抑菌作用有一定的加强效应。     

Itraconazole versus terbinafine (LAMISIL®): which is better for the treatment of onychomycosis?

Objectives To compare the efficacy, safely and tolerability of oral terbinafine with itraconazole in patients with toenail onychomycosis treated for 4 months. Setting Departments of dermatology of six universities and one private clinic. Design Double-blind double-dummy, multicentric, multinational, parallel-group therapeutic trial, involving 179 patients with toenail onychomycosis. Patients were randomly treated with either 200 mg/day oral itraconazole or 250 mg/day terbinafine for 4 months. After the 4th month both treatment groups received oral placebo for another 8 months. The total duration of the study was therefore 12 months. After the 12th month a final evaluation of efficacy was performed in 167 patients (85 on itraconazole and 82 on terbinafine) and a final evaluation of tolerability was performed in 175 patient. Results The dermatophytes identified at the initial visit were Trichophyton rubrum (82.1%), Trichophyton mentagrophytes (14%) and others (3.9%), The mycological cure rates at the end of the 4th and 12th months were 54.9% and 95.3% in the terbinafine group and 51.8% and 84.31% in the itraconazole group (the difference between the groups was. statistically significant at the 12th month, P < 0.04). Clinical cure was achieved by 8.5% and 9.4% of the patients in the terbinafine and itraconazole groups at the 4th month (not significant. NS) and these rates increased to 57.8% and 62.9%. respectively, at the 12th month (difference between groups NS, P > 0,05). A complete mycological cure associated with clinical improvement over 50%. was observed at the 4th month in 50% of the patients treated with terbinafine and 49.4% of the patients treated with itraconazole which was not statistically significant (NS). At the 12th month the rates increased to 95.4% with terbinafine and 75.7% with itraconazole (statistically significant. P < 0.001). Seven patients of the terbinafine group and 9 patients of the itraconazole group presented drug-related side effects (NS). Six patients (6.3%) discontinued the study due to adverse events in the itraconazole group hut no patient discontinued in the terbinafine group. At entry into the study all subjects in both groups presented normal values in liver function tests which remained unchanged throughout the study in the patients of the terbinafine group. One patient of the itraconazole group presented small increases in SGOT and SGPT associated with abdominal pain and nausea.     

Long-term outcomes in the treatment of toenail onychomycosis

Most clinical studies in subjects with toenail onychomycosis end with a final assessment at 48–52 weeks. This fails to take full account of the physiology of toenail growth, as toenails can take up to 12–18 months to grow out fully. Accurate assessment of long-term outcomes therefore requires follow-up of at least 2 years after completion of the study. We have evaluated long-term outcomes of treatment in the patients whom we contributed to two multicentre studies of oral therapy for toenail onychomycosis caused by dermatophyte infection. In the first, a dose-finding study for terbinafine (Lamisil^®), the high rates of mycological and clinical cure achieved by terbinafine at week 48 were maintained more than 2 years after completion of the study. In the second, a comparative study between terbinafine and itraconazole (Sporanox^®), the excellent mycological and clinical cure rates achieved by terbinafine at week 48 were again maintained more than 2 years after completion of the study. By contrast, the failure and relapse rates seen with itraconazole were much higher. Other studies undertaken in recent years have confirmed these positive findings with respect to terbinafine, and have demonstrated its superiority over itraconazole in maintaining mycological and clinical cure over long periods. These long-term benefits of terbinafine probably relate to its primarily fungicidal action against dermatophytes, compared to the fungistatic action of itraconazole and other triazole agents. Future clinical studies should therefore incorporate at least 2 years' follow-up.     

Fluconazole vs. Itraconazole in the treatment of tinea versicolor

Ninety patients with tinea versicolor were randomly assigned to treatment with either a single 450-mg dose of fluconazole, two 300-mg doses of fluconazole given 1 week apart, or itraconazole 200 mg daily for 7 days. At the end of treatment, the cure rate for itraconazole (20%) was significantly higher ( P  = 0.024) than that for fluconazole 450 mg (0%). When cure plus improvement was considered, response rates among the three treatment groups were comparable (97, 100, and 97% for fluconazole 450 mg, fluconazole 300 mg, and itraconazole, respectively). Failure rates at the end of treatment were low (0–3%). Clinical response rates achieved at the end of treatment generally were maintained at 1 month, but tended to decrease at 2 months. Eradication at the end of treatment was not significantly different among the treatment groups (17, 33, and 38% for fluconazole 450 mg, fluconazole 300 mg, and itraconazole, respectively). At 1 month, the eradication rate was significantly higher ( P  = 0.012) for the two-dose than the single-dose fluconazole treatment group (97 and 70%, respectively). At 2 months, reinfection rates were 21, 20, and 4% for fluconazole 450 mg, fluconazole 300 mg, and itraconazole, respectively. No clinical adverse events occured, and no patients were withdrawn for laboratory abnormalities.     

In vitro antifungal susceptibility patterns of dermatophyte strains causing tinea unguium

BACKGROUND: Dermatophytes are the major responsible organisms in onychomycosis. Although recent antifungal agents have high success rates in treating this condition, lack of clinical response may occur in 20%. Antifungal drug resistance may be one of the causes of treatment failure. The need for in vitro antifungal drug resistance in daily practice is still under discussion. OBJECTIVE: We aimed to determine the in vitro susceptibility patterns of dermatophytes causing onychomycosis, against the traditionally available systemic antifungal agents terbinafine, itraconazole and fluconazole. METHODS: In total, 100 otherwise healthy patients with suspected onychomycosis were included. Nail clippings were cultured on Sabouraud dexrose agar, mycobiotic agar and dermatophyte test medium. Antifungal susceptibility tests were carried out, mainly following The National Committee for Clinical and Laboratory Standards (M38-P) protocol standard for filamentous fungi. Different concentrations of terbinafine (0.008-8 microg/mL), itraconazole (0.015-16 microg/mL) and fluconazole (0.06-64 microg/mL) were tested. Minimum inhibitory concentration end-point determination was chosen as 100% growth inhibition for terbinafine and 80% for azoles. RESULTS: Of the 100 nail samples, 43% grew dermatophytes. The main causative organism was Trichophyton rubrum (91%) followed by Trichophyton mentagrophytes (9%). Terbinafine had the lowest minimum inhibitory concentration (0.008 microg/mL) followed by itraconazole. Fluconazole showed the greatest variation in minimum inhibitory concentration (0.03-2 microg/mL) and had different susceptibility patterns for the two species. CONCLUSIONS: Of the three antifungals tested, terbinafine had the most potent in vitro antifungal activity against dermatophytes. Antifungal susceptibility tests would be useful to screen antifungal-resistant dermatophyte strains.