Lamisil scientific update |
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Drug Dev Ind Pharm. 2010 Jun 14. [Epub ahead of print]
Vaka SR, Murthy SN, O'Haver JH, Repka MA.
Department of Pharmaceutics, School of Pharmacy, University of Mississippi, University, MS, USA.
A platform for predicting and enhancing model drug delivery across the human nail plate.
Purpose: The objective of the present study was to assess the effect of pretreatment using chemical etchants on the delivery of terbinafine hydrochloride (TH) and 5-fluorouracil (5-FU) into and across the human nail plate. Methods: The TranScreen-N method was used to screen five potential etchants. Based on these results, the dorsal surface of nails was pretreated with chemical etchants, 1% or 10% (w/w) phosphoric acid (PA) or 10% (w/w) lactic acid (LA) gels, for a period of 60 seconds. The nail pretreated with a plain gel formulation (no PA or LA incorporated) was used as the control. Results: Despite the differences in physicochemical properties between TH (log P = 3.3) and 5-FU (log P = -0.83), the in vitro permeation as well as drug load of these drugs in the nail plate was enhanced because of pretreatment with the PA gels, whereas LA pretreatment failed to enhance the drug load and permeation. Optical microscopic and atomic force microscopy studies revealed that the PA enhanced the trans-ungual drug delivery by decreasing the keratin density of the dorsal layer of the nail plate and by microstructural alterations. Conclusions: This study demonstrated that pretreatment of the nail plate with PA (1% or 10%, w/w) for a short duration could be a potential method of improving the efficiency of topical monotherapy treatment for nail diseases.
Acta Derm Venereol. 2010 May;90(3):239-45.
Alsterholm M, Karami N, Faergemann J.
Department of Dermatology and Venereology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Antimicrobial activity of topical skin pharmaceuticals - an in vitro study.
The aim of this study was to investigate the antimicrobial activity of currently available topical skin pharmaceuticals against Candida albicans, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. The agar dilution assay was used to determine the minimal inhibitory concentration for cream formulations and their active substances. Corticosteroid formulations with the antiseptics clioquinol or halquinol were active against all microbes. The hydrogen peroxide formulation was primarily active against staphylococci. Clotrimazole, miconazole and econazole showed an effect against staphylococci in addition to their effect on C. albicans. In contrast, terbinafine had no antibacterial effect. Fusidic acid was active against staphylococci, with slightly weaker activity against S. pyogenes and no activity against C. albicans or E. coli. In summary, some topical skin pharmaceuticals have broad antimicrobial activity in vitro, clioquinol and halquinol being the most diverse. In limited superficial skin infection topical treatment can be an alternative to systemic antibiotics and should be considered. With the global threat of multi-resistant bacteria there is a need for new, topical, non-resistance-promoting, antimicrobial preparations for the treatment of skin infections.
J Dermatol. 2010 Apr;37(4):367-73.
Arakaki O, Asato Y, Yagi N, Taira K, Yamamoto Y, Nonaka K, Hosokawa A, Kayo S, Hagiwara K, Uezato H.
Division of Dermatology, Department of Organ-oriented Medicine, School of Medicine, University of the Ryukyus, Uehara, Nishihara, Okinawa, Japan.
Phaeohyphomycosis caused by Exophiala jeanselmei in a patient with polymyalgia rheumatica.
An 87-year-old man, a gardener in Okinawa, first noticed a tumor on the dorsum of his right hand in November 2005. He had been taking prednisolone for the treatment of polymyalgia rheumatica since 2000. A nearby dermatologist incised the tumor for pus drainage in February 2006. In April of the same year, the dome-like tumor reappeared. The same treatment was repeated. Because the culture of the pus revealed fungi at that time, terbinafine hydrochloride and minocycline were administrated under the diagnosis of a deep fungal infection. After a short remission, the tumor recurred in November of the same year and in May and August of 2007 regardless of the repeated incision and pus drainage. He was referred to our hospital on 27 September 2007. His first physical examination at our outpatient office showed a skin-colored, well-demarcated, multilocular, cystic subcutaneous tumor on the dorsum of his right hand. Histopathological examination revealed a pseudocyst with fibrous walls of connective tissue. Continuous, bead-like hyphae, positive with periodic acid-Schiff stain and Grocott stain, were found within the pseudocyst. Morphological and molecular biological examinations of the separately cultured specimens identified the causative agent as Exophiala jeanselmei. The entire cyst was removed under local anesthesia, and an artificial dermis made of silicon membrane was applied to the wound. Skin graft was performed in November after confirming no recurrence of the fungal infection. Terbinafine hydrochloride 125 mg/day has continued. No recurrence has been observed up to now.
G Ital Dermatol Venereol. 2010 Jun;145(3):415-23.
Gianni C.
Department of Dermatology, S. Raffaele Scientific Institute, Milan, Italy.
Update on antifungal therapy with Terbinafine.
Terbinafine, a syntethic antifungal of allylamine class, has fungicidal activity against dermatophytes, moulds and certain dimorphic fungi and fungistatic activity against Candida albicans. Following oral administration the terbinafine is absorbed rapidly (>70%) and reaches within 2 hours the peak plasma concentration. The drug is highly lipophilic and keratophilic and is highly bound to plasma protein (>90%) with a bioavailability of 70% to 80%. The drug is rapidly delivered and it is present in the stratum corneum, sebum, nails and hair for months after stopping the medication. The drug has been proven to be the choice treatment in the therapy of onychomycosis as it is very effective, well tolerated and has a relatively low potential for drug interactions. The pharmacologic and pharmacokinetic properties of terbinafine give strong support to the possibility that the pulse therapy may be equally effective in onychomycoses, possibly reducing medication costs and drug exposure. Several therapeutic patterns have been proposed: weekly intermittent terbinafine (500 mg/d for 1 week each month for 4 months), or single-dose terbinafine (1000 mg per month for 4 months). Use of topical terbinafine 1% may be practical where the tinea involvement is not extensive or chronic. Recently, the terbinafine is available in a novel topical solution (film-forming solution - FFS) effective in the treatment of tinea pedis (athlete's foot).
J Eur Acad Dermatol Venereol. 2009 Dec 17. [Epub ahead of print]
Sigurgeirsson B, Olafsson J, Steinsson J, Kerrouche N, Sidou F.
Dermatology Center, Kopavogur, Iceland.
Efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years.
Abstract Background Standard treatment for onychomycosis often results in less than half of subjects achieving disease-free nails. Onychomycosis is even more challenging to treat as relapses and re-infections are common. Objective To determine if a prophylactic effect exists when a treatment with amorolfine nail lacquer (ANL), with half the frequency of the standard regimen, is instituted following successful treatment of dermatophytic toenail onychomycosis with matrix involvement. Methods Efficacy and safety of a group treated with ANL (once every 2 weeks) were compared with that of an untreated group in a 36-month (3 years), single-centre, randomized, open-label, comparison study. Subjects to be included in the study were required to be cured of confirmed onychomycosis with matrix involvement after an initial treatment with either ANL + oral terbinafine or oral terbinafine alone in a previous study. Prophylaxis of onychomycosis was assessed by global recurrence rate, confirmed onychomycosis, clinical recurrence and mycological recurrence. Results A total of 52 subjects were enrolled (26 in each group) in the study. Throughout the study, recurrences occurred more quickly in the untreated group compared with that in the ANL group. Statistically significant differences were observed at month 12 (ANL, 8.3%; untreated, 31.8%; P = 0.047). At endpoint, 70.8% of the subjects treated with ANL remained cured compared to 50% in the untreated group (P = 0.153). Recurrence was delayed by nearly 200 days for the ANL group compared with that of the untreated group. Amorolfine was safe and well tolerated during the study, with no treatment-related adverse events. Conclusion These results suggest that amorolfine nail lacquer may be effective and is safe for use as a prophylactic treatment for the recurrence of onychomycosis.
Nippon Ishinkin Gakkai Zasshi. 2009;50(4):253-7.
Kobayashi K, Sawada M, Ninomiya J, Ishizaki S, Harada T, Tanaka M.
Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
[Usefulness of pathological diagnosis for two cases of candidal onychomycosis] [Article in Japanese]
We report two cases of candidal onychomycosis with severe nail deformities. Case 1: The patient was an 81-year-old man who complained of onycholysis and nail deformity of the right forefinger nail which had occurred over a period of a year. He had no obvious previous illness. Case 2: The patient was an 81-year-old woman who complained of nail deformity with periungual erythema which had occurred over a period of several months. She had been treated with oral corticosteroid for bronchial asthma and with Ca blocker for hypertension for a long period. The initial KOH-prepared direct microscopy in each case failed to detect any spores or pseudohyphae. Therefore, an incisional biopsy was performed in both cases. Histopathological findings demonstrated numerous fungal elements with similar appearance of dermatophytes in the middle to lower level of the horny cell layer by PAS and Grocott staining in each case. Candida albicans was isolated and identified by cultivation on ATG agar. In case 1, oral itraconazole (100 mg/day) was administered for 14 weeks, which was effective clinically and mycologically. In case 2, however, a coadministered drug (Ca blocker), oral terbinafine (125 mg/day) was not effective mycologically. Therefore, after having changed the antihypertensive agent, oral itraconazole (100 mg/day) was administered for 16 weeks, which was effective clinically and mycologically.
Nippon Ishinkin Gakkai Zasshi. 2009;50(4):207-12.
Katoh T.
Division of Dermatology, Saiseikai Kawaguchi General Hospital.
[Guidelines for diagnosis and treatment of mucocutaneous candidiasis] [Article in Japanese]
This document summarizes current knowledge about diagnosis and treatment of candidiasis affecting the skin and oral mucosa. Several clinical forms of mucocutaneous candidiasis are distinguished depending on a patient's age and infected site, e.g. Candida intertrigo, erythema mycoticum infantile, erosio interdigitalis blastomycetica, candidal paronychia and onychia, Candida onychomycosis, and oral candidiasis. The diagnosis of candidiasis is confirmed by observation of mycelial forms on microscopic examination. Since Candida yeasts (especially C. albicans) are normal inhabitants of the skin and oral mucosa, it must always be noted that positive culture does not always indicate the presence of candidal infection. The pathogenicity of Candida species is relatively low, and some special conditions are required for tissue invasion by the fungus. Predisposing factors, such as disturbances of the cutaneous and mucosal microenvironment and systemic or local immunosuppression, should be checked in patients with recurrent infection. Therapy for cutaneous candidiasis is dominated by topical antifungal agents. Azole antifungal cream (e.g., bifonazole, ketoconazole, neticonazole hydrochloride, lanoconazole and luliconazole) is most effective. Terbinafine hydrochloride and amorolfine hydrochloride are also useful. Cutaneous candidiasis usually requires a shorter duration of topical treatment (1-2 weeks) than superficial dermatophyte infections. For candidal paronychia and onychomycosis, oral therapy with itraconazole is recommended. The daily dose of itraconazole should be taken for several months, while its pulse therapy for candidiasis is not approved in Japan. Itraconazole oral solution is commonly used for oral candidiasis, and miconazole gel is also effective.
Nippon Ishinkin Gakkai Zasshi. 2009;50(4):199-205.
Ogawa Y, Hiruma M.
Department of Dermatology, Juntendo University.
[Dermatophytosis: a summary of dermatomycosis as a proposal for future revision of the guidelines] [Article in Japanese]
In preparing guidelines for dermatomycosis (tinea, trichophytia, dermatophytosis), we have primarily summarized the disease types and treatments as described in 4 textbooks used in Japan and abroad. We present our classification draft based on these following descriptions. In Japan, any dermatophytosis other than favus or tinea imbricata is considered to be tinea, while outside Japan, favus and tinea imbricata are also classified as tinea. Tinea capitis is classified together with trichophytia superficialis capillitii and kerion celsi, in a group that tends to include asymptomatic carriers. Most textbooks generally classify trichophytia profunda of the glabrous skin and granuloma trichophyticum as subtypes of tinea corporis. Tinea faciei can easily be misdiagnosed, but in many cases can be distinguished from tinea corporis by its specific clinical picture. Tinea unguium is regarded as one type of onychomycosis. We present a summary of dermatomycosis treatment as a proposal for future revision of the guidelines. One of the problems in the treatment of tinea capitis is that the safety of itraconazole (ITZ) and terbinafine hydrochloride (TBF) in children has not been established. Severity criteria for concomitant use of oral medications in the treatment of tinea pedis remains to should be established. Although many clinical studies concerning tinea unguium have been published, 3 of the 4 textbooks we consulted clearly stated that most of those studies were conducted by pharmaceutical companies. Further studies on the etiology and disease severity of tinea unguium are needed.
Vet Dermatol. 2008 Dec;19(6):405-10.
Nuttall TJ, German AJ, Holden SL, Hopkinson C, McEwan NA.
The University of Liverpool Small Animal Teaching Hospital, Leahurst Campus, Chester High Road, Neston, Cheshire CH64 7TE, UK.
Successful resolution of dermatophyte mycetoma following terbinafine treatment in two cats.
Microsporum canis sensitive to itraconazole and terbinafine was isolated from two cats presented with generalized dermatophytosis and dermatophyte mycetoma. Itraconazole therapy was withdrawn through lack of efficacy in one cat (a Persian) and unacceptable adverse effects in the other (a Maine Coon). Both cats achieved clinical and mycological cure after 12-14 weeks therapy with 26-31 mg kg(-1) terbinafine every 24 h per os (PO). Clinical signs in the Maine Coon resolved completely after 7 weeks treatment. Four weeks of therapy with additional weekly washes with a 2% chlorhexidine/2% miconazole shampoo following clipping produced a 98% reduction in the Persian cat's mycetoma, which was then surgically excised. Recurrent generalized dermatophytosis in the Persian cat has been managed with pulse therapy with 26 mg kg(-1) terbinafine every 24 h PO for 1 week in every month. No underlying conditions predisposing to dermatophytosis were found in either cat despite extensive investigation. Terbinafine administration was associated with mild to moderate lethargy in the Persian cat, but no other adverse effects or changes in blood parameters were seen. To the best of the authors' knowledge this is the first report of a dermatophyte mycetoma in a Maine Coon and of successful resolution of this condition in cats following terbinafine therapy.
Plast Reconstr Surg. 2008 Dec;122(6):186e-194e.
Rampazzo A, Salgado CJ, Gharb BB, Mardini S, Spanio di Spilimbergo S, Chen HC.
Department of Plastic Surgery, E-Da Hospital, I-Shou University, Kaohsiung County, Taiwan, Republic of China.
Donor-site morbidity after free ileocolon flap transfer for esophageal and voice reconstruction.
BACKGROUND: Radical excision of advanced hypopharyngeal and laryngeal tumors usually compromises both swallowing and speech. Among the available reconstruction methods, the free ileocolon flap allows rehabilitation of both functions in one stage. The donor-site morbidity of this flap has not been addressed in head and neck cancer patients. METHODS: A retrospective study was conducted in 34 patients between April of 2003 and December of 2007 to investigate donor-site morbidity in patients undergoing reconstruction with free ileocolon flaps. Complications such as diarrhea, upper gastrointestinal tract distress, bowel leak, abscess, or hernia formation were evaluated. Significant association of diarrhea and upper gastrointestinal distress, previous abdominal operations, systemic diseases, primary versus secondary reconstruction, flap length, and postoperative chemotherapy were subsequently evaluated. Differences were considered significant for values of p
J Med Microbiol. 2008 Dec;57(Pt 12):1581-4.
Chang BP, Sun PL, Huang FY, Tsai TC, Lin CC, Lee MD, Chen YC, Sheu JC, Tsai JD.
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
Paecilomyces lilacinus peritonitis complicating peritoneal dialysis cured by oral voriconazole and terbinafine combination therapy.
Fungal peritonitis (FP) is a serious complication in patients on continuous ambulatory peritoneal dialysis (CAPD). We report a case of CAPD-related FP caused by Paecilomyces lilacinus in a 15-year-old uraemic boy. The infection was successfully treated by combination therapy consisting of oral voriconazole and terbinafine, which has not been previously reported in the treatment of FP.
Infection. 2008 Dec;36(6):594-6. Epub 2008 Nov 8.
Fischer N, Ruef Ch, Ebnöther C, Bächli EB.
Dept. of Medicine, Medical Clinic, University Hospital, Zurich, Zurich, Switzerland.
Rhinofacial Conidiobolus coronatus infection presenting with nasal enlargement.
Rhinofacial Conidiobolus coronatus infection is a rare form of zygomycosis in humans living in the northern hemispheres. Most human cases are observed in the periequatorial areas of Africa, Asia, or South America. Only limited information regarding optimal treatment is available. We report a case of rhinofacial C. coronatus infection in an emigrated Sudanese patient. The infection was successfully treated with terbinafin and itraconazole for 12 months. Diagnosis was confirmed by microbiological culture from a tissue biopsy. Antimicrobial susceptibility testing of this organism was not predictive of optimal therapy.
Acta Dermatovenerol Alp Panonica Adriat. 2007 Dec;16(4):170-3.
Khaled A, Chtourou O, Zeglaoui F, Fazaa B, Jones M, Kamoun MR.
Department of Dermatology, Charles Nicolle Hospital, Tunis, Tunisia.
Tinea faciei: a report on four cases.
Four cases of tinea faciei that were observed at the Department of Dermatology of Charles Nicolle Hospital in Tunis are reported. All patients were females, ages 54 (patient 1), 38 (patient 2), 30 (patient 3), and 50 (patient 4). The lesions lasted 1 year, 2 months, 4 months, and 1 month, respectively. Tinea faciei was initially suspected in three patients, whereas for the second patient eczema was initially suspected. She was first treated topically with corticosteroids leading to exacerbation. Through mycological examination, Trichophyton rubrum was isolated in three patients, but was negative in patient 2. Three patients recovered completely after one month of griseofulvin associated with topical terbinafine. Patient 3 was topically treated because she was pregnant. Erythematous lesions of the face must be checked for fungi.
Am J Med Sci. 2007 Dec;334(6):497-8.
Joubert M, Reznik Y, Verdon R.
Department of Endocrinology, University Hospital of Caen, Caen Cedex, France.
"Rescue" bilateral adrenalectomy in paraneoplastic Cushing's syndrome with invasive Aspergillus fumigatus infection.
We report the case of a patient with life-threatening Aspergillosis during paraneoplastic Cushing's syndrome. Anticortisolic drug ketoconazole was unable to lower severe hypercortisolism and despite antifungal treatment available at this time (liposomal amphotericine B and terbinafine), Aspergillus fumigatus infection was uncontrolled and extensive. "Rescue" bilateral adrenalectomy was performed to control hypercortisolism, leading to rapid fungal infection cure. We emphasize surgical management of hypercortisolism to achieve rapid blunting of cortisol production in a such life-threatening situation.
Am J Clin Dermatol. 2007;8(6):357-64.
Korting HC, Kiencke P, Nelles S, Rychlik R.
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität München, Munich, Germany.
Comparable efficacy and safety of various topical formulations of terbinafine in tinea pedis irrespective of the treatment regimen: results of a meta-analysis.
BACKGROUND: Terbinafine has been widely used with major success as a topical antifungal therapy for tinea pedis (athlete's foot). Its efficacy and safety have been validated in several clinical trials, which have demonstrated clinical efficacy for the drug after only 1 week of treatment when applied once daily, a reflection of the high fungicidal potency of the drug and its ability to form a depot in the upper skin layer. To improve patients' compliance further, a terbinafine-containing film-forming solution has been developed for single-dose therapy of athlete's foot. This novel formulation delivers terbinafine in high amounts and for a prolonged period of time into the skin, making one-shot treatment feasible. Over the past years there have been a variety of trials evaluating use of topical terbinafine addressing different pharmaceutical formulations, treatment durations, and application frequencies, but a detailed meta-analysis of these trials has not been conducted to date. OBJECTIVE: The present study is the first meta-analytic evaluation of the available data on the efficacy (clinical and mycologic cure rates) and safety (adverse events) of all topical forms of terbinafine for the treatment of tinea pedis. METHODS: An international, systematic literature search of 12 electronic databases (including MEDLINE, EMBASE, and Cochrane databases) using a pre-specified search strategy was conducted in March 2006. This meta-analysis included only randomized controlled trials in which terbinafine had been used for topical treatment of tinea pedis in comparison with placebo or an active control. Studies of all available topical formulations of terbinafine, frequencies of application, and durations of treatment were included. RESULTS: Of 100 identified articles published between 1990 and 2006, 19 met the criteria for analysis. These 19 studies involved 2899 patients with clinical and mycologic diagnoses of tinea pedis (nine placebo-controlled trials and ten active-controlled trials). Efficacy analysis demonstrated that the mycologic cure rate was significantly superior with terbinafine compared with placebo (relative risk [RR] 3.17; p < 0.001). No significant differences in efficacy were found amongst different formulations of terbinafine, treatment durations, or frequencies of application. Comparable results were obtained with respect to clinical cure rate for terbinafine compared with placebo (RR 2.75; p < 0.001). Comparison of the efficacy of terbinafine versus active control indicated a nonsignificant difference in favor of terbinafine with regard to mycologic cure rate (RR 1.03; p = 0.423) and clinical cure rate (RR 1.09; p = 0.11). The median duration of treatment was also shorter with terbinafine (1 week) compared with active controls (2 weeks). Analysis of the placebo-controlled studies showed that there was no significant difference in the risk of adverse events with terbinafine compared with placebo (RR 1.34; p = 0.34). Likewise, no significant differences in adverse events were found between terbinafine and active controls (RR 1.08; p = 0.72). CONCLUSION: Terbinafine is very well tolerated in any topical pharmaceutical formulation and also has high efficacy as a cure for tinea pedis, irrespective of type of pharmaceutical formulation, treatment duration, and frequency of application, including the recently established one-shot regimen. In addition, terbinafine has an apparently unique advantage over other antifungal agents with respect to the required duration of treatment for tinea pedis.
Indian J Dermatol Venereol Leprol. 2007 Nov-Dec;73(6):393-6.
Jaiswal A, Sharma RP, Garg AP.
Department of Dermatology and Venereology, L. L. R. M. Medical College, Meerut, Uttar Pradesh, India.
An open randomized comparative study to test the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in the treatment of onychomycosis.
BACKGROUND: Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts and molds. AIMS: To study the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in onychomycosis. METHODS: A clinical comparative study was undertaken on 96 Patients of onychomycosis during the period between August 2005 to July 2006. Forty-eight patients were randomly assigned in group A to receive oral terbinafine 250 mg, one tablet twice daily for seven days every month (pulse therapy); 24 patients in group B to receive oral terbinafine pulse therapy plus topical ciclopirox olamine 8% to be applied once daily at night on all affected nails; and 24 patients in group C to receive oral terbinafine pulse therapy plus topical amorolfine hydrochloride 5% to be applied once weekly at night on all the affected nails. The treatment was continued for four months. The patients were evaluated at four weekly intervals till sixteen weeks and then at 24 and 36 weeks. RESULTS: We observed clinical cure in 71.73, 82.60 and 73.91% patients in groups A, B and C, respectively; Mycological cure rates against dematophytes were 88.9, 88.9 and 85.7 in groups A, B and C, respectively. The yeast mycological cure rates were 66.7, 100 and 50 in groups A, B and C, respectively. In the case of nondermatophytes, the overall response was poor: one out of two cases (50%) responded in group A, while one case each in group B and group C did not respond at all. CONCLUSION: Terbinafine pulse therapy is effective and safe alternative in treatment of onychomycosis due to dermatophytes; and combination therapy with topical ciclopirox or amorolfine do not show any significant difference in efficacy in comparison to monotherapy with oral terbinafine.
Rev Inst Med Trop Sao Paulo. 2007 Sep-Oct;49(5):293-5.
Nweze EI, Ogbonna CC, Okafor JI.
Department of Microbiology, University of Nigeria, Nsukka, Nigeria. newezemeka@yahoo.com
In vitro susceptibility testing of dermatophytes isolated from pediatric cases in Nigeria against five antifungals.
The antifungal activities of itraconazole, ketoconazole, fluconazole, terbinafine and griseofulvin were tested by broth microdilution methods against 71 isolates of dermatophytes isolated from Nigerian children. Most drugs were very active against all the dermatophytes and the MIC 90 ranged from 0.03 to 8.0 microg/mL. This appears to be the first documented data on the antifungal susceptibility testing of isolates of dermatophytes from Nigerian children.
J Huazhong Univ Sci Technolog Med Sci.
Chen S, Li S, Liu Z, Wu Y, Tu Y, Li J.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology .
Comparison of the effects of three different anti-fungus drugs on Candida albicans of murine vaginal mucosa.
The present study is to compare the therapeutic effects of three different anti-fungal in the treatment of experimental vaginitis caused by Candida albicans. The study revealed that Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis caused by C. albicans in mice.
To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and
intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mice, the
fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans
after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then
respectively treated with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden of the
fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time
points after the beginning of the drug treatment. The fungal burdens in the vaginal lavage fluids taken at
different time points from the mice treated with terbinafine were significantly higher than those taken at
corresponding time points from mice treated with fluconazole or itraconazole (P<0.01). The fungal burdens in the
vaginal lavage fluids taken from mice 1 week after the beginning of the treatment with terbinafine remained at a
relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd
day of the treatment from mice treated with itraconazole or fluconazole group and the fungal burden on the 3rd day
of the treatment in these mice were at a very low level, suggesting that fluconazole or itraconazole were highly
effective for the treatment. However, the difference in the therapeutic effect between the two drugs was not
significant (P>0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of
fungal vaginitis caused by C. albicans in mice.
Scand J Infect Dis. 2007;39(1):87-90.
Bhat SV, Paterson DL, Rinaldi MG, Veldkamp PJ.
Division of Infectious Diseases, The University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Scedosporium prolificans brain abscess in a patient with chronic granulomatous disease: successful combination therapy with voriconazole and terbinafine.
The present valuable study revealed the effectiveness of terbinafine and voriconazole against brain abscesses with Scedosporium prolificans caused by chronic granulomatous disease.
A patient with chronic granulomatous disease developed brain abscesses with Scedosporium prolificans. In vitro
susceptibility revealed a synergistic effect of terbinafine and voriconazole. He received therapy with both these
antifungals which resulted in disappearance of the brain abscesses. This is the first reported cure of a CNS S.
prolificans infection in an immunocompromised host.
Ann Pharmacother. 2007 May;41(5):880-4.
Paredes AH, Lewis JH.
Department of Internal Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Terbinafine-induced acute autoimmune hepatitis in the setting of hepatitis B virus infection.
The given study is to report a case of terbinafine-induced autoimmune hepatitis in a patient with chronic hepatitis B infection. The study concluded that healthcare practitioners should pay attention to the manufacturer's warning that terbinafine not be used in patients with underlying hepatic disease.
OBJECTIVE: To report a case of terbinafine-induced autoimmune hepatitis in a patient with chronic hepatitis B
infection. CASE SUMMARY: A 57-year-old Taiwanese male with chronic hepatitis B virus (HBV) began an oral regimen of
terbinafine 250 mg once daily for dermatophyte toenail onychomycosis, despite the manufacturer's recommendation not
to use the drug in patients with liver dysfunction. The patient's liver enzyme levels were within normal limits at
initiation of therapy. Immediately prior to concluding the 12 week treatment course, he became anorexic with
malaise and subsequently developed ascites and jaundice. After a visit to an outside emergency department and
positively trending liver function test levels, he was referred to our liver clinic. The patient was taking no
other medications or herbal supplements, did not drink alcohol, and did not appear to suffer a flare of HBV
infection. The diagnosis was supported by the presence of transient autoantibodies and a liver biopsy consistent
with acute autoimmune drug injury. Three weeks after terbinafine was discontinued, peak levels of aspartate
aminotransferase (1282 IU/L), alanine aminotransferase (1044 IU/L), and bilirubin (5.9 mg/dL) were noted; his
platelet level had decreased to 77 x 10(3)/mm3. He was treated with supportive care that included vitamin K for
coagulopathy, diuretics for ascites, and adefovir to prevent hepatitis B exacerbation. The patient's liver function
studies began to normalize 6 weeks after terbinafine was discontinued. DISCUSSION: Terbinafine-induced
hepatobiliary dysfunction, due to hepatocellular injury, cholestasis, or mixed form, has been reported, but this is
the first case of autoimmune hepatitis supported by serologic, biochemical, and biopsy results. Use of the Naranjo
probability scale revealed a probable relationship between the patient's hepatitis and terbinafine. Furthermore,
the Roussel Uclaf Causality Assessment Method, a scoring system that specifically assesses the likelihood of
drug-induced elevated levels of liver-associated enzymes, also supported a probable relationship. The pathogenesis
of most drug-induced autoimmune hepatitis remains speculative, likely involving hapten-carrier complex and the
cytochrome P450 isoenzymes. In this patient, his chronic HBV carrier state may have predisposed him to this
autoimmune reaction. CONCLUSIONS: Healthcare practitioners should heed the manufacturer's warning that terbinafine
not be used in patients with underlying hepatic disease.
Therapie. 2006 May-Jun;61(3):251-4.
Dupont B.
Maladies Infectieuses et Tropicales, Universite Paris 5, Hopital Necker-Enfants Malades, Paris, France.
Use of topical antifungal agents][Article in French
The given review explained that Tinea capitis responds to oral griseofulvine, on the other hand a topical antifungal must be added to eradicate contagious conidia. Whatever the localisation is, an other superficial site of infection must be looked for and a source of infection should be investigated and eradicated.
Topical antifungal agents are not absorbed when given orally. They act by direct contact on the fungus, this type of action requires the simultaneous presence of antifungal and fungus for a minimum of time. There are a large number of compounds belonging to different families of antifungals: polyens, azoles, allylamine and morpholine and antiseptic substances. The treatment of oropharyngeal candidiasis is based on topical antifungal agents: amphotericin B or nystatin, imidazoles such as clotrimazole or miconazole. Systemic antifungal agents are indicated in case or poor compliance to topical agents, in prophylaxis of highly relapsing disease, in oesophageal candidiasis and in Candida onychomycosis. A topical antifungal agent is the first choice to treat Candida intertrigo. In any case predisposing factors should be eradicated or amended. Infection to Malassezia spp. are treated topically with azoles or selenium sulphur. Oral ketoconazole is an alternative in severe cases. Dermatophytosis requires a systemic antifungal treatment such as terbinafine in chronic, dry, moccassin type palmoplantar infection and for onychomycosis. Intertrigo and tinea corporis are treated with topical agents such as azoles, terbinafine or tolnaftate. Tinea capitis responds to oral griseofulvine, however a topical antifungal must be added to eradicate contagious conidia. Whatever the localisation is, an other superficial site of infection must be looked for and a source of infection should be investigated and eradicated.
J Eur Acad Dermatol Venereol. 2003 Nov;17(6):627-40.
Gupta AK, Adamiak A, Cooper EA.
Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook site) and the University of Toronto, Toronto, Canada.
The efficacy and safety of terbinafine in children.
Different study data suggest that terbinafine is effective and safe using treatment regimens that involve short duration therapy for treating paediatric superficial fungal infections such as tinea capitis.. The evidence from the given review favours the use of terbinafine in the treatment of superficial infections in children.
Terbinafine is an allylamine antifungal agent that has been effective and safe in the treatment of superficial and some deep mycotic infections in adults. An increasing amount of data is available where terbinafine has been used in the paediatric population to treat superficial fungal infections, in particular tinea capitis. The data suggest that terbinafine is effective and safe using treatment regimens that involve short duration therapy, leading to an increased compliance and providing a cost-effective means of treating paediatric superficial fungal infections such as tinea capitis. Terbinafine has been approved for the treatment of tinea capitis in many countries worldwide, and provides good efficacy rates for Trichophyton tinea capitis using shorter regimens than the gold standard griseofulvin. The adverse events profile for children is similar to that in adults with few adverse effects associated with its use. The evidence favours the use of terbinafine in the treatment of superficial infections in children.
J Eur Acad Dermatol Venereol. 2004 Mar;18(2):155-9.
Devliotou-Panagiotidou D, Koussidou-Eremondi TH.
Department of Dermatology, Aristoteles University of Thessaloniki, Mycological Laboratory of the State Hospital for Skin and Venereal Diseases, Chalkidikis 51, GR-54644, Thessaloniki, Greece.
Efficacy and tolerability of 8 weeks' treatment with terbinafine in children with tinea capitis caused by Microsporum canis: a comparison of three doses.
The following study is to compare the efficacy, safety and tolerability of an 8-week course of oral terbinafine at different doses. The given successful study concluded that the administration of terbinafine at a dose of either 6-7 or 7-12.5 mg/kg/day for 8 weeks is safe and effective for the treatment in children of tinea capitis caused by Microsporum canis.
BACKGROUND: Tinea capitis caused by Microsporum canis is the most common mycosis of the scalp in preschool and school-aged children in Greece. OBJECTIVE: To compare the efficacy, safety and tolerability of an 8-week course of oral terbinafine at different doses. METHODS: Patients received oral terbinafine at doses ranging from 3.3 to 12.5 mg/kg/day for 8 weeks, as follows: group A, terbinafine 3.3 to 6.0 to 7.0 mg/kg/day (23 patients); group C, terbinafine > 7.0 to 12.5 mg/kg/day (37 patients). Fungal microscopy and cultures were performed 4 weeks before the start of the treatment, at the end of the treatment (week 8) and at a follow-up visit at week 16. RESULTS: At week 8 mycological cure was achieved in one patient (2.7%) in group A, in 21 patients (91.3%) in group B and in 34 patients (97.1%) in group C. At week 16 mycological cure was achieved in one patient (2.7%) in group A, in 22 patients (95.7%) in group B and in 35 patients (100%) in group C. There was a statistically significant difference (P < 0.0005) between dose level and efficacy of terbinafine at the end of the treatment period and also at the follow-up visit at week 16. Five patients (three in group A and two in group C) discontinued treatment because of adverse events. CONCLUSIONS: The administration of terbinafine at a dose of either 6-7 or 7-12.5 mg/kg/day for 8 weeks is safe and effective for the treatment in children of tinea capitis caused by M. canis.
Ann Hepatol. 2003 Jan-Mar;2(1):47-51.
Zapata Garrido AJ, Romo AC, Padilla FB.
Hospital Christus Muguerza, Monterrey, Nuevo Leon, Mexico.
Terbinafine hepatotoxicity. A case report and review of literature.
The given case report and review about Terbinafine hepatotoxicity. The given case was experienced jaundice and abdominal pain after a seven-day course of treatment with terbinafine for onychomycosis. After starting treatment with ursodeoxycholic acid and ademethionine the patient’s liver tests normalized in the sixth months after stopping terbinafine.
We report a 53-year old Mexican female who developed liver dysfunction following a seven-day course of treatment with terbinafine for onychomycosis. She presented with jaundice and abdominal pain. Her serum bilirubin levels showed a peak value of 23.2 mg/dL seven weeks after discontinuing the medication. Infectious causes (hepatitis viruses A, B and C) were excluded. Imaging studies of the abdomen did not reveal any abnormalities. Serum iron and ceruloplasmin levels were normal. Autoantibodies were negative. A liver biopsy revealed necrosis and mononuclear infiltration of the parenchyma, mainly along the sinusoids and surrounding the portal spaces and biliary ducts. Eosinophil infiltration of the portal spaces was also noted. Treatment with ursodeoxycholic acid and ademethionine was started. Her liver tests normalized in the sixth months after stopping terbinafine.
Int J Cancer. 2004 Aug 10;111(1):51-9.
Ho PY, Liang YC, Ho YS, Chen CT, Lee WS.
Graduate Institute of Cellular and Molecular Biology, Taipei Medical University, Taipei, Taiwan.
Inhibition of human vascular endothelial cells proliferation by terbinafine.
In this study the scientists demonstrated that terbinafine (TB) at a range of concentrations (0-120 microM) dose-dependently decreased cell number in cultured human umbilical vascular endothelial cells (HUVEC). The scientists demonstrated for the first time that TB can inhibit the angiogenesis.
We have demonstrated previously that terbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, suppresses proliferation of various cultured human cancer cells in vitro and in vivo by inhibiting DNA synthesis and activating apoptosis. In our study, we further demonstrated that TB at a range of concentrations (0-120 microM) dose-dependently decreased cell number in cultured human umbilical vascular endothelial cells (HUVEC). Terbinafine was not cytotoxic at a concentration of 120 microM, indicating that it may have an inhibitory effect on the cell proliferation in HUVEC. The TB-induced inhibition of cell growth rate is reversible. [(3)H]thymidine incorporation revealed that TB reduced the [(3)H]thymidine incorporation into HUVEC during the S-phase of the cell-cycle. Western blot analysis demonstrated that the protein levels of cyclin A, but not cyclins B, D1, D3, E, CDK2 and CDK4, decreased after TB treatment. The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Pretreatment of HUVEC with a p21 specific antisense oligonucleotide reversed the TB-induced inhibition of [(3)H]thymidine incorporation. Taken together, these results suggest an involvement of the p21-associated signaling pathway in the TB-induced antiproliferation in HUVEC. Capillary-like tube formation and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of TB. These findings demonstrate for the first time that TB can inhibit the angiogenesis.
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