terbinafine, Lamisil
Comparative study of antifungal activity of sertaconazole, terbinafine, and bifonazole against clinical isolates of Candida spp., Cryptococcus neoformans and dermatophytes.

Carillo-Munoz AJ, Tur-Tur C.

Department of Microbiology, ACIA, Barcelona, Spain. ajcm.acia bcn.servicom.es

The in vitro activity of sertaconazole was compared with that of terbinafine and bifonazole against 180 Candida spp., Cryptococcus neoformans yeasts and 53 dermatophytes. Minimum inhibitory concentrations (MICs) were determined by a microdilution method in Sabouraud's buffered liquid medium (pH 5.6). Sertaconazole (arithmetic mean MIC 1.24 mg/l) was statistically more active than bifonazole (MIC 6.54 mg/l) and terbinafine (MIC 12.61 mg/l) against yeasts strains, MIC values for sertaconazole being generally and specifically lower for each tested yeast species. MIC for C. parapsilosis (0.26 mg/l) demonstrated a higher activity of sertaconazole against this species, in contrast to C. tropicalis (MIC 1.49 mg/l). Against dermatophytes, MIC for terbinafine (0.05 mg/l) was lower than sertaconazole (MIC 0.41 mg/l) and bifonazole (MIC 1.04 mg/l). These results, obtained under the same experimental conditions, confirm the good antifungal activity of sertaconazole against both yeasts and dermatophytes with lower MICs obtained in the topical application. This in vitro activity correlates with the clinical efficacy of sertaconazole compared with other antifungal agents.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9395851&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Effects of itraconazole and terbinafine on Leishmania major lesions in BALB/c mice.

Zakai HA, Zimmo SK.

Medical Technology Program, Faculty of Medicine & Allied Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. drzakai hotmail.com

The effects of two antifungal compounds, the azole itraconazole and the allylamine terbinafine, on Leishmania major infections in mice are reported. Sixty BALB/c mice were each inoculated subcutaneously with metacyclic promastigotes of L. major at the base of the tail. From 4 weeks post-inoculation, 40 of the mice were treated for 4 weeks (20 with itraconazole and 20 with terbinafine) and the rest were left untreated. Lesion sizes were estimated weekly for 10 weeks post-infection. Both drugs appeared effective in treating the cutaneous lesions but response to itraconazole was faster and, at the end of the experiment, the mean size of the lesions on the mice treated with itraconazole was smaller than that of the lesions on the terbinafine-treated mice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11214097&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Terbinafine pulse therapy is effective in tinea capitis.

Gupta AK, Adam P.

Department of Medicine, Sunnybrook Health Science Center and the University of Toronto, Canada.

Terbinafine pulse therapy was found to be effective and safe in the treatment of tinea capitis in an open study of 13 children (age range 3-13 years, mean 6.4 years, 7 males, 6 females, Tricohphyton tonsurans 7 patients, T. violaceum 6 patients). Each pulse of active therapy lasted 1 week with a 2 weeks off period between the first two pulses and a 3 weeks off period between the second and third pulses of treatment. The dosage of terbinafine was determined by the weight of the child: >40 kg, 250 mg/day, 20 to 40 kg, 125 mg/day and <20 kg, 62.5 mg/day. Twelve (92.3%) of 13 children achieved complete clinical and mycological cure when evaluated 12 weeks after starting therapy with the number of pulses for complete (clinical and mycological) cure being one pulse (two patients with mild severity of tinea capitis), two pulses (four patients with mild disease) and three pulses (mild disease: two patients, moderate disease: two patients, and severe disease: three patients). One child with moderate severity disease failed to clear after three pulses of terbinafine. There were no adverse effects observed in any of the 13 patients during the course of therapy. All the parents found it easy to administer therapy and the compliance was high.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9496808&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans.

Barchiesi F, Di Francesco LF, Compagnucci P, Arzeni D, Giacometti A, Scalise G.

Institute of Infectious Diseases & Public Health, University of Ancona, Italy.

A chequerboard titration broth microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was applied to study the in-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against 30 strains of Candida albicans isolated from the oral cavities of AIDS patients. MICs were determined spectrophotometrically at 490 nm and read at either 24 h or 48 h. The end-point was defined as the drug concentration resulting in > or = 90% inhibition of growth relative to control growth. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 93% (28 of 30) of terbinafine-amphotericin B interactions, in 47% (14 of 30) of terbinafine-fluconazole interactions and in 43% (13 of 30) of terbinafine-itraconazole interactions; antagonism (FIC > 2.0) was not observed. Where synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination. Reading the MICs on day 2 did not significantly affect the mode of interaction of terbinafine-triazoles, while for terbinafine-amphotericin B the proportion of synergic interactions dropped from 93% (28 of 30) to 30% (nine of 30; P = 0.0001). Antagonism was not observed for any drug combination even at 48 h. Minimum fungicidal concentrations (MFCs) of all drugs alone and in combination were determined against five isolates. Neither terbinafine nor the two triazoles showed fungicidal activity when tested alone or in combination. The fungicidal activity of amphotericin B was slightly enhanced when combined with terbinafine, there being a decrease of two-fold dilutions in the amphotericin B MFCs against all five isolates tested. Thus terbinafine enhances the activities of amphotericin B and triazoles against C. albicans in vitro. Clearly, clinical studies are warranted to elucidate further the potential utility of these combination therapies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9511038&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro and in vivo antidermatophyte activities of NND-502, a novel optically active imidazole antimycotic agent.

Niwano Y, Kuzuhara N, Kodama H, Yoshida M, Miyazaki T, Yamaguchi H.

Research Center, Nihon Nohyaku Co., Ltd., Kawachinagano, Osaka, Japan. mntoxlab os.luice.or.jp

In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole antimycotic agent, were compared with those of two existing antifungal agents, lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal activity against Trichophyton spp.; its MIC was 1 to 4 times lower than that of lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in polyethylene glycol 400) was more effective than that with a 0.5% solution of either lanoconazole or terbinafine for eradicating fungi from the infected feet. When the duration of treatment was shortened to 3 days, a topical 1% solution of NND-502 achieved a complete mycological cure, while topical 1% solutions of lanoconazole and terbinafine did not.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9559824&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro activities of terbinafine against cutaneous isolates of Candida albicans and other pathogenic yeasts.

Ryder NS, Wagner S, Leitner I.

Novartis Research Institute, Vienna, Austria. neil.ryder pharma.novartis.com

Terbinafine is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier studies indicated that the drug had little activity against Candida albicans. In contrast, clinical studies have shown topical and oral terbinafine to be active in cutaneous candidiasis and Candida nail infections. In order to define the anti-Candida activity of terbinafine, we tested the drug against 350 fresh clinical isolates and additional strains by using a broth dilution assay standardized according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1 microg/ml for reference C. albicans strains. For 259 clinical isolates, the MIC at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 microg/ml (fluconazole, 0.5 microg/ml), and the MIC90 was 4 microg/ml (fluconazole, 1 microg/ml). Terbinafine was highly active against Candida parapsilosis (MIC90, 0.125 microg/ml) and showed potentially interesting activity against isolates of Candida dubliniensis, Candida guilliermondii, Candida humicola, and Candida lusitaniae. It was not active against the Candida glabrata, Candida krusei, and Candida tropicalis isolates in this assay. Cryptococcus laurentii and Cryptococcus neoformans were highly susceptible to terbinafine, with MICs of 0.06 to 0.25 microg/ml. The NCCLS macrodilution assay provides reproducible in vitro data for terbinafine against Candida and other yeasts. The MICs for C. albicans and C. parapsilosis are compatible with the known clinical efficacy of terbinafine in cutaneous infections, while the clinical relevance of its activities against the other species has yet to be determined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9593126&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Fungicidal versus fungistatic activity of terbinafine and itraconazole: an in vitro comparison.

Hazen KC.

Department of Pathology, University of Virginia Medical Center, Charlottesville 22908, USA.

BACKGROUND: The ratio of fungicidal to fungistatic activity of two new antifungal agents, itraconazole and terbinafine, against the causative organisms in onychomycosis may have clinical relevance. OBJECTIVE: This study compared the fungistatic and fungicidal activity of terbinafine and itraconazole against clinical isolates of dermatophytes and Candida species causing onychomycosis. METHODS: The antifungal agent was added to suspensions of dermatophyte conidia and hyphal fragments (5 x 10(3) to 5 x 10(4) fungal elements/ml) that had been preincubated to allow hyphal formation. Cell suspensions of Candida species (1 to 5 x 10(3) cells/ml) were not preincubated before drug exposure. Macrobroth and macrobroth dilution assays were used to test antifungal susceptibility of dermatophytes and yeasts, respectively. An agent was considered fungicidal if the minimal fungicidal concentration (MFC) to minimal inhibitory concentration (MIC) ratio was < or = 4 and fungistatic if the ratio was > 4. Cell death was also visualized by a vital stain. RESULTS: For both itraconazole and terbinafine, the MIC for dermatophytes was low. The MFCs and MFC/MIC ratios for terbinafine against dermatophytes were lower than for itraconazole; the fungicidal activity of terbinafine was excellent and initiated rapidly (by 7 hours) and that of itraconazole was poor (fungicidal activity was not evident until 10 to 12 hours). For yeasts, the MICs were higher than for dermatophytes, and the differences between itraconazole and terbinafine were less pronounced. CONCLUSION: Both itraconazole and terbinafine inhibit growth of dermatophytes. The more rapid fungicidal activity of terbinafine may have clinical relevance in the treatment of onychomycosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9594935&dopt=Abstract terbinafine Lamisil