Gustavo Giusiano

Terbinafine susceptibility patterns for onychomycosis-causative dermatophytes and Scopulariopsis brevicaulis

The in vitro antifungal activity of terbinafine against 521 clinical isolates of seven species of dermatophytes, including four onychomycosis-causative species, as well as five Scopulariopsis brevicaulis isolates was determined by a modified Clinical and Laboratory Standards Institute microdilution method. Results showed a high antifungal activity of terbinafine against all dermatophyte isolates (geometric minimal inhibitory concentration (MIC)=0.026 microg/mL; concentration inhibiting 50% of mycological growth (MIC50)=0.03 microg/mL; and concentration inhibiting 90% of mycological growth (MIC90)=0.06 microg/mL). The geometric mean MICs against onychomycosis-causative dermatophyte species was lower (0.024 microg/mL) than the global MIC. However, the in vitro activity of terbinafine against S. brevicaulis was considerably lower (geometric mean MIC=1.38 microg/mL) in comparison with dermatophytes. The antifungal activity of itraconazole was lower than that of terbinafine against these fungi. These data confirm the high in vitro antifungal activity of terbinafine against dermatophytes, under standardised conditions.

Sertaconazole: updated review of a topical antifungal agent

Sertaconazole is an imidazole-type antifungal agent that has shown considerable in vitro activity against pathogenic fungi. Various studies carried out in animal models, clinical and toxicologic trials have confirmed the value of sertaconazole in the topical treatment of superficial mycoses in dermatology and gynecology. After several years of clinical experience in the topical treatment of dermatophytosis and Tinea versicolor, the substance has been approved for gynecologic candidiasis in Europe. Sertaconazole has a wide action spectrum that includes yeasts and dermatophyte fungi, and it is also active against bacteria, mainly Gram-positive cocci, making it highly efficient in the treatment of polymicrobial infections. The recent approval of the molecule by the US Food and Drug Administration, and the appearance of a new formulation of sertaconazole for the treatment of onychomycoses on a weekly administrative basis, are all data relevant to the process of marketing the product.

Sertaconazole Nitrate Shows Fungicidal and Fungistatic Activities against Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum, Causative Agents of Tinea Pedis

ABSTRACT The fungistatic and fungicidal activities of sertaconazole against dermatophytes were evaluated by testing 150 clinical isolates of causative agents of tinea pedis, Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. The overall geometric means for fungistatic and fungicidal activities of sertaconazole against these isolates were 0.26 and 2.26 μg/ml, respectively, although values were higher for T. mentagrophytes than for the others. This is the first comprehensive demonstration of the fungicidal activity of sertaconazole against dermatophytes.

In Vitro Antifungal Activity of Sertaconazole Nitrate Against Recent Isolates of Onychomycosis Causative Agents

Topical antifungal treatment of superficial mycoses can have high relapse rates and recurrence after stopping treatment 1. Onychomycosis is the most common nail disorder in adults, accounting for up to 50% of all nail diseases, specially in adults and the elderly 2-6. Candida infections account for 5-10% (Candida albicans and Candida parapsilosis) of all cases of onychomycosis and about 5% of cases are due to non-dermatophyte molds. The most commonly isolated dermatophyte is Trichophyton rubrum, with Scopulariopsis brevicaulis being the most common non-dermatophyte 2-7. Epidemiological data indicate a high rate of clinical failure, over 25%, due to problems of nail penetration and retention times of active antifungal concentrations. Antifungal treatment compliance is low (<51%) and many patients require oral therapy in cases of previous clinical failure or extended affected areas involving nail matrix. The aim of this study was to assess the in vitro antifungal activity of sertaconazole nitrate against clinical isolates of onychomycosis-causing agents and to compare this activity to those of amorolfine, cyclopiroxolamine, bifonazole, fluconazole and terbinafine. Sertaconazole, an azole derivative, acts by inhibiting ergosterol biosynthesis and damaging cell integrity 8. It has a broad spectrum of activity against yeasts, dermatophytes as well as Gram-positive bacteria 1,2-15. The 100 clinical isolates of yeasts, dermatophytes and opportunistic molds from patients with onychomycosis recruited at some health centers were tested in duplicate with a standardized method of microdilution in RPMI 1640 21-23. The clinical isolates were the following: C. parapsilosis (30), T. rubrum (29), S. brevicaulis (10), C. albicans (5), C. guilliermondii (4), T. mentagrophytes (4), C. famata (3), C. glabrata (3), C. tropicalis (3), C. intermedia (1), C. krusei (3), Cryptococcus laurentii (2), C. lusitaniae (1), Fusarium sp. (1) and Rhodotorula minuta (1). Drug concentrations ranged between 0.016 μg/ml to 16 μg/ml for all antifungal drugs except fluconazole (minimum inhibitory concentration (MIC) range from 0.25 to 256 μg/ml). MIC ranges and geometric means were calculated for each species-drug combination. MIC50 and MIC90 were considered as the concentrations of antifungal agent that were able to inhibit 50% and 90% of the isolates, respectively, and were determined for species including more than 10 isolates. Sertaconazole (STZ) antifungal activity (MIC 0.28 μg/ml) was higher than those obtained for terbinafine (TRB), amorolfine (AMR), cyclopiroxolamine (CPO), bifonazole (BFZ) and fluconazole (FLZ) (Table 1). Antifungal susceptibility patterns of reference strains and quality control strains were in agreement with those previously described 16-18. STZ (MIC 0.31 μg/ml) (Table 1) was the most active antifungal agent against yeast isolates, followed by FLZ, CPO, TRB, AMR and BFZ. The antifungal activity against yeasts was species-dependent for all antifungal drugs tested. STZ was especially active against C. albicans (MIC 0.153 μg/ml), and C. krusei (MIC 0.03 μg/ml). A statistically significant difference (Student’s t test, p<0.001), was found in favor of STZ compared to BFZ, FLZ, AMR and CPO. The rank order of antifungal potency against yeasts was STZ > FLZ ≈ CPO > TRB > AMR > BFZ. A detailed analysis of pathogenic groups revealed a greater antifungal activity of most drugs against dermatophytes, TRB and STZ being the most active. STZ activity was also in the same range as TRB and AMR and was higher than other azole derivatives for T. rubrum (MIC 0.063 μg/ml). The rank order of antifungal activity against dermatophytes was AMR ≈ TRB ≈ STZ > BFZ ≈ CPO > FLZ. Susceptibility patterns of opportunistic filamentous fungi were similar for STZ, BFZ and TRB. STZ (MIC 6.02 μg/ml), CPO (MIC 3.31 μg/ml) and AMR (MIC 0.55 μg/ml) were more active than BFZ and TRB. There was a statistically difference between STZ and TRB and FLZ (p<0.001) in favor of STZ against opportunistic filamentous fungi. The rank order of activity against non-dermatophyte molds was AMR ≈ CPO > STZ > TRB ≈ BFZ > FLZ. Despite many advances in antifungal drug development and therapy, onychomycosis remains difficult REPRINT

Activity of Caspofungin and Voriconazole against Clinical Isolates of Candida and Other Medically Important Yeasts by the CLSI M-44A Disk Diffusion Method with Neo-Sensitabs Tablets

In vitro activity of caspofungin and vori conazole against 184 clinical isolates of Candida and other medically important yeasts in comparison with that of fluconazole, ketoconazole, itraconazole and amphotericin B was determined by using a disk diffusion method (Neo-Sensitabs) standardized according to the recommendations of the CLSI documents M44-A and M44–S1 (same medium: Mueller-Hinton plus methylene blue; inoculum and minimal inhibitory concentration/zone breakpoints). Seventy-two percent of clinical isolates were susceptible to caspofungin, 23.6% showed an intermediate susceptibility (most of them were Candida parapsilosis) and 4.3% were resistant (values for Candida spp. were 71.2, 23.8 and 5%, respectively). For voriconazole, 96.7% of clinical isolates were susceptible and 3.3% were resistant (Candida spp.: 96 and 3.8%, respectively). Both caspofungin and voriconazole showed high activity against a wide variety of clinically important yeasts.

Sertaconazole: an antifungal agent for the topical treatment of superficial candidiasis

Sertaconazole is a useful antifungal agent against mycoses of the skin and mucosa, such as cutaneous, genital and oral candidiasis and tinea pedis. Its antifungal activity is due to inhibition of the ergosterol biosynthesis and disruption of the cell wall. At higher concentrations, sertaconazole is able to bind to nonsterol lipids of the fungal cell wall, increasing the permeability and the subsequent death of fungal cells. Fungistatic and fungicidal activities on Candida are dose-dependent. The antifungal spectrum of sertaconazole includes deramophytes, Candida, Cryptococcus, Malassezia and also Aspergillus, Scedosporium and Scopulariopsis. Sertaconazole also shows an antimicrobial activity against streptococci, staphylococci and protozoa (Trichomonas). In clinical trials including patients with vulvovaginal candidiasis, a single dose of sertaconazole produced a higher cure rate compared with other topical azoles such as econazole and clotrimazole, in shorter periods. Sertaconazole has shown an anti-inflammatory effect that is very useful for the relief of unpleasant symptoms

Sertaconazole Antifungal Profile Determined by a Microdilution Method versus Nine Topical Substances against Dermatophyte Fungi

Antifungal activity and in vitro inhibition time for sertaconazole (STZ) and 9 other topical drugs, namely amorolfine, bifonazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, terbinafine, and tioconazole were determined against 124 clinical isolates of dermatophyte (12 species) fungi by the microdilution method in a liquid medium and the measurement of optical density. STZ’s antifungal activity was not always affected by the tested dermatophyte genus, as was the case with the remaining antifungals. In vitro antifungal activity was at the same level for all the studied azole derivatives, but, in terms of partial inhibitory concentrations, STZ starts its in vitro inhibitory activity in a shorter time than the other tested substances, particularly in those incubation periods when the growth of the dermatophyte fungi was more developed.