Mycological Cures Research Articles

A phase III randomized controlled clinical trial evaluating the efficacy and safety of naftifine 2% cream versus terbinafine 1% cream in patients with superficial fungal infection of the skin

Background: Dermatophytosis is the prevailing fungal infection, typically addressed through topical, systemic antifungal medications, or a combination of both. Naftifine hydrochloride, belonging to the allylamine group, is a topical antifungal, exhibiting fungicidal properties alongside antibacterial and anti-inflammatory effects. This study evaluated the efficacy and safety of naftifine hydrochloride 2% w/w in 268 patients with dermatophytosis versus terbinafine hydrochloride 1% w/w. Methods: The drugs were applied daily for two weeks, with the primary endpoint being a clinical cure at the end of the treatment. Secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Results: In both groups, most patients experienced both clinical and mycological cures, with composite cures observed in 94.07% of the test group and 87.97% of the reference group. The global assessment of efficacy was 3.59 in the test group and 3.48 in the reference group, showing no notable difference between the two groups. All adverse events in both groups were mild and resolved within four days. Overall tolerability was comparable between the study groups. Conclusions: The study concluded that topical naftifine was effective and safe in patients with dermatophytosis and its efficacy and safety were found comparable to topical terbinafine.

Pediatric tinea capitis in Jilin Province: analyzing previous results from a new perspective.

To investigate the current etiological, diagnostic, and therapeutic characteristics of tinea capitis in children in Jilin Province. Sixty pediatric patients with tinea capitis were enrolled between August 2020 and December 2021. Data on calcofluor white (CFW) fluorescence microscopy, fungal culture, Wood's lamp examination, dermoscopy, treatment, and follow-up were collected and analyzed. 1. Of all the enrolled patients, 48 had a history of animal contact, mostly with cats and dogs. Fifty-one strains were isolated, of which 46 were Microsporum canis (M. canis). 2. All enrolled patients were examined using fluorescence microscopy, and 59 were positive. Forty-one cases of tinea alba were examined using Wood's lamp, and 38 were positive. Forty-two cases of tinea alba were examined using dermoscopy, and 39 demonstrated specific signs. Effective treatment manifested as a fading bright green fluorescence, decreased mycelial/spore load, reduced specific dermoscopic signs, and hair regrowth. 3. Treatment was terminated in 23 and 37 cases based on mycological and clinical cures, respectively. No recurrence occurred during follow-up. 1. M. canis is the predominant pathogen causing tinea capitis in children in Jilin Province. Animal contact is considered the main risk factor. 2. CFW fluorescence microscopy, Wood's lamp, and dermoscopy can be used to diagnose ringworms and follow-up patients. 3. Both mycological and clinical cures can be the endpoint of adequate treatment for tinea capitis.

Randomized controlled trial comparing long‐pulsed 1064‐Nm neodymium: Yttrium‐aluminum‐garnet laser alone, topical amorolfine nail lacquer alone, and a combination for nondermatophyte onychomycosis treatment

Studies of the laser treatment of nondermatophyte mold (NDM) onychomycosis are limited. Long-pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) 1064-nm laser has been introduced as an adjuvant dermatophyte onychomycosis treatment. To investigate the efficacy and safety of long-pulsed Nd:YAG 1064-nm laser for NDM onychomycosis treatment, compared with topical amorolfine nail lacquer alone and a combination treatment. This randomized controlled trial was conducted at the Nail Clinic, Siriraj Hospital. Patients diagnosed with NDM were included and randomly assigned to three treatment groups: laser at 1month interval (1064-nm Nd:YAG at a fluence of 35J/cm2 , pulse width 30ms, and pulse rate 1.0Hz); topical amorolfine nail lacquer alone; and a combination treatment. Sixty patients completed the study. The patients treated with the laser, amorolfine, and the combination achieved mycological cure rates of 35%, 60%, and 65%, respectively (P=.05), while 10%, 30%, and 30% of the patients in the respective groups were clinically cured. The mean durations to the mycological cures in the patients treated with laser, amorolfine, and the combination were 5.9, 4.8, and 5.2months, respectively. By comparison, the corresponding mean durations to the clinical cures were 6.9, 6.5, and 5.9months. Both the times to the mycological cures and the clinical cures did not differ significantly between the groups (P=.290 and P=.309, respectively). There were no serious complications with the laser treatment. Laser alone achieved only a 30% mycological cure rate for NDM onychomycosis. The combination treatment yielded similar outcomes to the topical treatment alone.

Laser therapies for onychomycosis – critical evaluation of methods and effectiveness

The number of medical devices designed specifically to treat onychomycosis has recently increased, although their mechanism of action is not clear. We evaluated available laser therapies for onychomycosis by reviewing the existing literature. Twenty-two reports, published in peer-reviewed journals and as white papers out of 926 initial search results conveyed enough details to be included in this study. In most cases, the methodology of the trials described in the papers we reviewed was not comprehensive and the reporting of outcomes was not unified. We therefore found it hard to compare different clinical trials to one another. The majority of studies (81.82%) reported using an Nd:YAG laser device to treat onychomycosis. A total of 47.37% of the studies which used a 1064 device (and 47.83% of all studies we reviewed) reported that all treated patients responded positively to laser therapy. A total of 60% of studies reported achieving a complete cure (no clinical symptoms, nor negative mycology) in at least 50% of the treated patients. A low number of adverse events and their mild intensity were consistently reported across all studies, which makes this form of therapy particularly attractive to patients with contraindications for receiving systemic antifungal medication. In order to achieve more unified, comparable studies in the future, we suggest that researchers report a minimum set of outcome measurements: the calculation of the infected nail area pre- and posttreatment, as well as the number of patients achieving mycological, clinical and complete cures.

Fusarium onychomycosis: prevalence, clinical presentations, response to itraconazole and terbinafine pulse therapy, and 1-year follow-up in nine cases.

Invasive fusariosis is an infection with Fusarium spp. that primarily affects patients with hematologic malignancies and hematopoietic cell transplant recipients. Wounds, digital ulcers, onychomycosis, and paronychia are the typical cutaneous portals of entry. Early management of mycotic nails in immunocompromised and diabetic hosts is crucial to prevent life-threatening disease. We report nine cases of Fusarium onychomycosis (F. dimerum, n = 5; F. oxysporum, n = 3; Fusarium spp., n = 1) in immunocompetent hosts and their response to itraconazole and terbinafine pulse therapy. The patients received either itraconazole 400 mg daily or terbinafine 500 mg daily for 7 d/month; two pulses for fingernails and three pulses for toenails. Of the 68 confirmed cases of onychomycosis, eight (11.7%) were Fusarium spp.; the ninth patient was culture positive but microscopy negative and responded well to itraconazole. Distal subungual onychomycosis was the commonest clinical manifestation (seven of nine), one had proximal subungual onychomycosis, and total onychodystrophy was noted on four patients. Associated paronychia was marked on 66.7% (six of eight) patients. Itraconazole was given to six patients/25 nails and terbinafine to three patients/20 nails. All nine patients completed treatments, but one defaulted at 12 months follow-up. The efficacy parameters were clinical cure (CC) and mycological cure (MC). At month 12 after the start of treatment, the response was itraconazole CC 13 of 25 (52%)/MC four of six (66.6%) and terbinafine CC four of eight (50%)/MC one of two (50%). Recurrence was noted in four of 13 (30.7%) and eight of 13 (61.5%) cured nails in the itraconazole group within 3 and 12 months, respectively. Fusarium onychomycosis was clinically indistinguishable from other onychomycosis. Both itraconazole and terbinafine pulse therapy were only partially effective on Fusarium onychomycosis. Antifungals that are more effective should be sought.

Trichophyton rubrum DNA strain switching increases in patients with onychomycosis failing antifungal treatments.

The dermatophyte Trichophyton rubrum is responsible for approximately 80% of onychomycosis cases. Genetic strain typing was developed to help elucidate its epidemiology and pathogenicity. To determine T.rubrum DNA strain types in North American patients with onychomycosis and to track the patients before and after their course of treatments. T.rubrum DNA strain types were determined by restriction fragment length polymorphisms in ribosomal DNA and Southern blotting from toenails that were cultured from 50 North American patients with onychomycosis prior to treatment. Some of the patients were subsequently typed from oral terbinafine (n=6), laser (n=9) or placebo (n=8) treatment groups. Three European DNA strains were obtained for comparison. DNA strains from the terbinafine group were tested for in vitro susceptibility to terbinafine. Six DNA strain types (A-F) accounted for 94% of T.rubrum DNA strains and corresponded to European isolates. Three DNA strains (6%) novel to North America were detected. DNA strain type switching occurred in all treatment groups: terbinafine (83%), laser (56%) and placebo (25%). Most of the switches (50%) observed in the terbinafine group coincided with mycological cures followed by relapse. Patients treated with laser therapy or placebo exhibited no intermittent cures. DNA strains from the terbinafine group were all susceptible to terbinafine in vitro. Nine T.rubrum DNA strains were identified in a North American population: three novel and six predominant to a European population. Although DNA strain type switching in onychomycosis is a natural phenomenon, with presence in the placebo group, increases following the course of failed onychomycosis treatment suggest an antifungal-induced response.

Terbinafine in the treatment of dermatophyte toenail onychomycosis: a meta‐analysis of efficacy for continuous and intermittent regimens

To compare mycological and complete cures of terbinafine continuous and intermittent regimens in the treatment of toenail onychomycosis. The PubMed database was searched using the terms "terbinafine", "onychomycosis", "continuous" and "pulse(d)" or "intermittent". The inclusion criteria were head-to-head comparison of terbinafine pulse and continuous regimens for dermatophyte toenail infections. Risk ratios were calculated for intention-to-treat and evaluable patient analyses, when possible. Pooled estimates for total and subgroup analyses were calculated using a random effect model, Mantel-Haenszel method and their probabilities were calculated with z-statistics. Nine studies from eight publications were included. Two continuous regimens and four intermittent regimens were investigated. A pooled risk ratio of 0.87 was obtained for intention-to-treat (95% CI: 0.79-0.96, P = 0.004, n = 6) and evaluable patient (95% CI: 0.80-0.96, P = 0.003, n = 8) analyses of mycological cure, favouring continuous terbinafine. For complete cure, pooled risk ratios of 0.97 (95% CI: 0.77-1.23, P = 0.82, n = 7) for intention-to-treat and 0.93 (95% CI: 0.76-1.13, P = 0.44, n = 9) for evaluable patient analyses showed equality of the two regimens. The pulse regimen that demonstrated consistently comparable results to the continuous terbinafine regimen was two pulses of terbinafine 250 mg/day for 4 weeks on/4 weeks off. Meta-analysis of published studies of toenail onychomycosis showed that a continuous terbinafine regimen is generally significantly superior to a pulsed terbinafine regimen for mycological cure. In contrast, some pulse terbinafine regimens were as effective as continuous terbinafine regimens for complete cure.

Treatment of Mild, Moderate, and Severe Onychomycosis Using 870- and 930-nm Light Exposure

We have previously reported the results of a clinical trial in which the Noveon laser was used to treat onychomycosis. In the 180-day follow-up therein it was noted that positive clinical impact was demonstrable by a clearly measurable decrease in positive fungal culture and a concomitant decrease in positive microscopy with periodic acid-Schiff-stained nail scrapings. Review of 270-day mycological data, which are now available, confirmed that there was further decrease in both measures. Indeed, 38% of the treated population had negative culture and microscopy, qualifying as "mycological cures." These mycological cures occurred in cases categorized as mild, moderate, and even severe disease.

Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children.

Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children.

Getting ahead of tinea capitis

The clinical presentation of tinea capitis (fungal infections of the scalp) ranges from mild scaling, to widespread alopecia, to markedly inflamed and suppurating kerions. Tinea capitis tends to be most common in children aged between 6 and 10 years, although adolescents and adults can contract fungal scalp infections and be asymptomatic carriers. The dermatophyte Trichophyton tonsurans causes between 50% and 90% of tinea capitis cases in the UK. However, the wide range of potential pathogens—especially among people originating in, or who have visited, foreign countries—and diagnostic difficulties mandate mycological testing. Fungi can infect the hair shaft, which protects the dermatophyte from topical antifungals. Yet despite tinea capitis being common, there are relatively few approved oral antifungals licensed for the condition. Nevertheless, a 6–12-week course of oral griseofulvin produces mycological cures in between 70% and 100% of tinea capitis cases. Topical antifungals may reduce transmission and nurses can encourage the family to follow some simple steps that reduce the risk of further infection.

Erratum

MycosesVolume 49, Issue 5 p. 441-441 Free Access Erratum This article corrects the following: A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis Shinichi Watanabe, Hisashi Takahashi, Takeji Nishikawa, Iwao Takiuchi, Nobuhiko Higashi, Katsutaro Nishimoto, Saburo Kagawa, Hideyo Yamaguchi, Hideoki Ogawa, Volume 49Issue 3Mycoses pages: 236-241 First Published online: April 25, 2006 First published: 08 August 2006 https://doi.org/10.1111/j.1439-0507.2006.01270.x Professor Shinichi WatanabeE-mail: watanabe@med.teikyo-u.ac.jp AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat In Watanabe et al. [1] Luliconazole was spelled incorrectly on Tables 2, 3 and 4. Please see below for the corrected tables. Table 2. Efficacy 1: clinical and mycological (KOH) comparison of the two treatment groups (FAS). Variable Clinical Mycological (KOH) Luliconazole Bifonazole Luliconazole Bifonazole Cure (patients) 91.5 (226/247) 91.7 (222/242) 76.1 (188/247) 75.9 (183/241) P-value 1 1 The primary response criterion defined as independent improvement of skin lesions (clinical) and mycological response. Table 3. Efficacy 2: Overall and mycological (culture) comparison of the two treatment groups (FAS). Variable Overall [clinical + mycologocal (KOH)] Mycological (culture) Luliconazole Bifonazole Luliconazole Bifonazole Cure (patients) 74.1 (183/247) 73.4 (177/241) 73.2 (82/112) 49.6 (57/115) P-value 0.918 0.0004 Overall clinical effects at week 4. Mycological (culture) was evaluated in KOH positive patients (LCZ: 112, BFZ: 117) in week 2. Table 4. Appearance of drug related adverse events in the two treatment groups. Safty analysis, n = 500. Adverse event Luliconazole (n = 253) Bifonazole (n = 243) Itching 2 3 Erythema 0 1 Skin-inflammation 0 1 Hotness 1 0 Irritation 2 2 Pain 1 0 Redness 1 1 Total no. of events 7 8 Total no. of patients (%) 5/253 (2.0%) 6/247 (2.4%) In addition, Luliconazole cream was supplied by Pola Chemical, Industries Inc., Yokohama, Japan, and bifonazole 1% cream was kindly supplied by Bayer Yakuhin, Ltd, Osaka, Japan. We apologise for these errors. Reference 1 Watanabe S, Takahashi H, Nishikawa T et al. A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis. Mycoses 2006; 49: 236– 241. Volume49, Issue5September 2006Pages 441-441 ReferencesRelatedInformation

Vulvovaginal candidiasis in a Flemish patient population

Increased resistance to fluconazole has been reported in oral, oesophageal and urinary Candida isolates, but this has not been observed commonly in genital tract isolates. The rate of isolation of Candida spp. and their susceptibility to amphotericin B, flucytosine and azoles were determined in a number of clinical practices in the city of Ghent, Belgium. Patients with symptomatic vulvovaginal candidiasis (VVC) were treated with fluconazole, and the mycological and clinical outcomes were evaluated. Isolates were identified as Candida albicans (78.6%), Candida guilliermondii (17.3%), Candida glabrata (2.6%) and Candida dubliniensis (1.3%). The rates of mycological and clinical cures were 79.5% and 100%, respectively. Women with recurrent VVC were infected more frequently by non-albicans Candida spp., but no association was found between the use of antifungal agents and the presence of non-albicans spp. In-vitro resistance to fluconazole was not detected, even among subsequent Candida isolates from nine patients for whom mycological cure was not achieved.

A randomized controlled trial assessing the efficacy of fluconazole in the treatment of pediatric tinea capitis

Griseofulvin is considered first-line therapy for tinea capitis, and the Physician's Desk Reference currently recommends 11 mg/kg per day microsize formulation for use in children. Diverse selective pressures have resulted in waning clinical efficacy of griseofulvin, such that higher doses and longer courses of treatment are required. These events have prompted the search for therapeutic alternatives. Fluconazole is one such treatment option, and a variety of studies using this drug have shown promise in the treatment of pediatric tinea capitis. We sought to assess the efficacy, safety, and optimal dose and duration of fluconazole therapy compared with standard-dose griseofulvin (11 mg/kg per day microsize formulation) in the treatment of pediatric tinea capitis. This randomized, multicenter, third-party-blind, 3-arm trial was designed as a superiority study to identify a therapeutically superior agent/regimen from the 3 treatment arms: (1) fluconazole 6 mg/kg per day for 3 weeks followed by 3 weeks of placebo, (2) fluconazole 6 mg/kg per day for 6 weeks, and (3) griseofulvin 11 mg/kg per day for 6 weeks. Efficacy variables included mycological, clinical, and combined outcomes. The primary efficacy variable was the combined outcome of the modified intent-to-treat population at week 6. Patient safety was assessed throughout the study. Statistical analysis of the efficacy variables was conducted by means of the Cochran-Mantel-Haenszel test. At the end of treatment, mycological cures were present in 44.5%, 49.6%, and 52.2% of the fluconazole 3-week, fluconazole 6-week, and griseofulvin groups, respectively. Analysis of the primary efficacy variable failed to identify any superior agent, and differences between the combined outcomes of the fluconazole 6-week and griseofulvin groups at week 6 were not significant (P = .32). Regarding mycological, clinical, and combined outcomes, no significant differences between the fluconazole 6-week and griseofulvin groups were detected at any time point in the study. No new safety concerns were raised by this trial, and the incidence of treatment-related adverse events noted in this study is concordant with previous reports. Patients in the fluconazole arms of the study fared similarly. At the end of the trial, the difference in mycological cures between the fluconazole arms was only 7.5%, and increases in the incidence of certain treatment-related adverse events were observed in the fluconazole 6-week group. Adjunctive topical therapies and the impact of infected contacts were not assessed in this trial. Systemic therapy with fluconazole 6 mg/kg per day and standard-dose griseofulvin produces comparable but low mycological and clinical cure rates. The limited efficacy of standard-dose griseofulvin and the lack of consensus regarding dose and duration of griseofulvin therapy in tinea capitis emphasize the need for controlled trials to identify optimal treatment parameters. Although the efficacy of fluconazole is no better than that of standard-dose griseofulvin, it may still be useful in select patients with a contraindication or intolerance to high-dose griseofulvin. The outcomes observed in this trial highlight the need to more clearly define the relative importance of adjunctive topical therapies and the evaluation and treatment of infected contacts as factors affecting cure rates.

Safety and efficacy of bedtime versus daytime administration of the miconazole nitrate 1200 mg vaginal ovule insert to treat vulvovaginal candidiasis

ABSTRACTObjective: Most vaginal products are self- administered at bedtime. Safety, efficacy, and therapeutic cure with bedtime versus daytime treatment of vulvovaginal candidiasis (VVC) were assessed to potentially improve compliance and convenience with vaginal antifungal treatment.Methods: A non-inferiority study evaluated 573 women with symptoms of VVC, randomized to daytime or bedtime self-administration of single dose of miconazole nitrate 1200 mg vaginal ovule (Monistat-1).* Monistat-1 is a registered trade name of Personal Products Company, a division of McNeil-PPC, Inc., Skillman, NJ, USAResults: Subjects (n = 149) were evaluated for efficacy in the Daytime group and 163 in the Bedtime group. In the Daytime group, 86 (57.7%) participants achieved therapeutic cure, with 105 (70.5%) and 111 (74.5%) exhibiting mycologic and clinical cures, respectively. In the Bedtime group, 83 (50.9%) subjects achieved therapeutic cure, with 104 (63.8%) and 120 (73.6%) exhibiting mycologic and clinical cures, respectively (NS). There was no significant difference in the incidence of side effects between the two groups. Median estimated time to initial relief of itching, burning and irritation was similar for both. Miconazole nitrate 2% cream was also applied twice daily to the vulvar area for external symptoms for up to 7 days. Test-of-cure was assessed 21 days–30 days following administration of intra-vaginal drug. Time to vulvovaginal symptomatic relief and the effect of activity following daytime administration on therapeutic cure were also assessed.Conclusion: The efficacy against a broad spectrum of pathogens and acceptability of daytime and bedtime administration of miconazole nitrate 1200 mg vaginal ovule were similar. These findings offer women a convenient option for treatment for VVC, whether self-managed or managed by their healthcare provider.

Oral Fluconazole in the Treatment of Tinea Versicolor

This study was designed to assess the efficacy, tolerability, and safety of oral fluconazole given at 300 mg once weekly for two weeks in the treatment of tinea versicolor. Enrolled into the study were 44 subjects with tinea versicolor, provisionally confirmed by the detection of fungal hyphae in KOH wet mounts and Wood's lamp examination. Four subjects were classified as dropouts because no information was obtained from them after the baseline visit. Subjects were treated for two weeks orally with fluconazole 300 mg weekly and followed at the 1st, 2nd, 4th and 12th weeks of treatment. The study included 40 subjects (26 males and 14 females, mean age 29 years, range 19-48 years). At the week 4 visit, 30 (75%) patients showed a complete cure and 31 (77.5%) patients showed mycologic cure. Ten (25%) patients had no significant response to therapy. At the final follow-up visit (week 12), none of the patients showing complete or mycologic cures exhibited a recurrence. No adverse effects were observed in any of the patients treated. We believe that, due to the low incidence of side effects, shorter treatment duration, and increased adaptation of the patients, fluconazole can be used in the treatment of tinea versicolor with confidence.

Itraconazole: a treatment with pharmacokinetic foundations

ItrafungolTM is a 10 mg/mL oral solution with the triazole itraconazole as active ingredient. It has recently been authorized in the UK, as a first country, for treatment of Microsporum canis dermatophytes in cats. The treatment schedule consisted of daily oral administration of 5 mg/kg body weight for three 1‐week periods, with each week of treatment followed by a week without treatment (following a consecutive week‐on, week‐off schedule). This schedule was designed on the basis of data from pilot trials and was confirmed in two specific trials in naturally‐infected cats. Clinical and mycological cures were monitored. In the second trial, plasma levels of itraconazole and its active metabolite, hydroxy‐itraconazole, were also assayed. Itraconazole is a very lipophilic compound that is readily distributed to fat tissue and sebaceous glands. It is also keratinophilic and accumulates in the stratum corneum of the skin and in hairs. These properties make it readily available at the site of infection. Itraconazole is metabolized into many metabolites of which only hydroxy‐itraconazole is antifungal. Plasma and hair levels of itraconazole and its active metabolite were determined in a separate trial in 24 cats after administration of ItrafungolTM at the recommended treatment schedule. Samples were analysed by HPLC. Both compounds were rapidly detectable. Repeated administration for 1 week resulted in mean peak plasma levels of 1.05 μg/mL at 1 h after the last dose of the week. Plasma concentrations dropped slowly during the week without treatment to around the quantification limit (5 ng/mL) just before the start of the second and third treatment periods. During these periods, there was a 20–30% increase of the 24‐h plasma concentrations towards the end of these periods. Median concentration of itraconazole in hair samples of these cats was 0.168 μg/g 24 h after the first dose. There was a clear increase of the median hair concentration after 1 week of treatment to 1.17 μg/g. At the end of the second period, the median concentration was 2.00 μg/g, and was 2.99 μg/g at the end of the third period. At the end of each of the intermittent periods without treatment, hair concentrations dropped 25–30% to median values of 0.8–1.5 μg/g. Two weeks after the last dose of the full treatment schedule, median hair concentrations were still 1.5 μg/g. Although hair concentrations of hydroxy‐itraconazole were below the quantification limit during the first and second treatment periods, they were quantifiable in an increasing number of hairs after the last period, with concentrations between 0.058 and 0.186 μg/g. Concentrations of both compounds together, and even itraconazole alone, are well above the MIC90 for Microsporum canis strains (0.1 μg/mL in various broth media) very shortly after the first dose and for up to 2 weeks after the last one. These data illustrate that the recommended treatment schedule (3 × 7 days of dosing) provides actual coverage of at least 7 weeks. Funding: Janssen Animal Health.

Achievement of complete mycological cure by topical antifungal agent NND-502 in guinea pig model of tinea pedis.

We examined the therapeutic effect of a 1% cream preparation of NND-502, a novel topical antifungal agent, in a guinea pig tinea pedis model produced by infecting the plantar skin of guinea pigs with Trichophyton mentagrophytes. Animals developing tinea pedis were divided into two groups: an untreated control group and a treated group. In the latter group, after confirming infection had been established, the infected animals were topically treated with the NND-502 cream once daily for one week. The animals were reared in a clean environment free from exposure to exogenous dermatophytes. At one week (5 weeks post-infection), 6 weeks (10 weeks post-infection) and 16 weeks (20 weeks post-infection) after completion of the treatment, plantar skin samples were taken from a certain number of both groups of animals. The results demonstrated that all of the animals in the untreated control group and none of those in the treated group were culture-positive in this animal model of tinea pedis. The topical treatment with NND-502 achieved a mycological cure. Thus NND-502 can be considered a promising candidate as a new anti-dermatophytic agent for topical use.

Itraconazole and Terbinafine Treatment of Some Nondermatophyte Molds Causing Onychomycosis of the Toes and a Review of the Literature

Background: Onychomycosis may be caused by dermatophytes (which form the majority of organisms), Candida species, and nondermatophyte molds. Objective: To evaluate the efficacy and safety of itraconazole and terbinafine in the treatment of some nondermatophyte molds that cause toe onychomycosis and to review the literature on the treatment of nondermatophyte mold toe onychomycosis using the oral antifungal agents. Patients and Methods: Patients with nondermatophyte mold toe onychomycosis were treated in an open, prospective manner with either itraconazole (pulse) or terbinafine therapy. In each instance, light microscopic examination was consistent with the diagnosis of a nondermatophyte mold. For each patient, mycological evaluation of the target nail resulted in 3 or more successive cultures yielding growth of the mold alone. Results: All 15 patients had onychomycosis of the toes which was of the distal and lateral type. The patients were treated with itraconazole given as the standard 3 pulses with additional pulses administered depending upon the response exhibited by the toe onychomycosis in the patient. Similarly, terbinafine was given for 12 weeks with additional therapy administered as dictated by the response. Efficacy parameters were mycological cure (MC) and clinical cure (CC). Mycological cure was negative light microscopic examination (KOH) and culture. Clinical cure was the appearance of a completely normal-looking nail. At month 12 from the start of treatment, the response was as follows: Scopulariopsis brevicaulis: itraconazole (MC 4/4, CC 2/4) and terbinafine (MC 0/1, CC 0/1), Fusarium species: itraconazole (MC 1/1, CC 1/1) and terbinafine (MC 0/1, CC 0/1), Aspergillus species: itraconazole (MC 5/6, CC 3/6), Alternaría alternata: itraconazole (MC 0/1, CC 0/1), and Onychocola canadensis: itraconazole (MC 1/1, CC 0/1). There were no significant clinical or laboratory adverse effects. Conclusions: In the present series itraconazole demonstrated efficacy against onychomycosis of the toenails caused by 5. brevicaulis and Aspergillus species. A review of the literature confirms our experience with itraconazole and further suggests that terbinafine may also demonstrate efficacy against cases of S. brevicaulis and Aspergillus toe onychomycosis. Additionally, reports in the literature suggest that pedal onychomycosis caused by Fusarium species may also show response to itraconazole and terbinafine. For the other species, there are fewer data, making it difficult to draw conclusions.

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.

The Use of Itraconazole to Treat Cutaneous Fungal Infections in Children

Background: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. Objective: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. Methods: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). Results: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. Conclusions: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.