In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen.

In vitro activities of new triazole antifungal agents, posaconazole and voriconazole, against oral Candida isolates from patients suffering from denture stomatitis.

Denture stomatitis is often treated with antifungal agents but recurrences or new episodes are common, and certain episodes can be resistant. New triazoles, such as posaconazole and voriconazole, may represent useful alternatives for management. In vitro activities of amphotericin B, nystatin, miconazole, fluconazole, itraconazole, posaconazole and voriconazole against 150 oral Candida (101 C. albicans, 18 C. tropicalis, 12 C. glabrata, 11 C. guilliermondii, 4 C. parapsilosis, 2 Saccharomyces cerevisiae, 1 C. dubliniensis and 1 C. krusei) from 100 denture wearers were tested by the CLSI M27-A3 method. Resistant isolates were retested by Sensititre YeastOne and Etest. Most antifungal agents were very active. However, 4 C. glabrata (33.3%), 2 C. tropicalis (11.1%), 6 C. albicans (5.6%) and 1 C. krusei were resistant to itraconazole. Posaconazole was active against 143 yeast isolates (95.3%): 6 C. albicans (5.9%) and 1 C. tropicalis (5.6%) were resistant. Geometric mean MICs were 0.036 µg/ml for C. parapsilosis, 0.062 µg/ml for C. albicans, 0.085 µg/ml for C. tropicalis, 0.387 µg/ml for C. guilliermondii and 0.498 µg/ml for C. glabrata. Voriconazole was active against 148 isolates (98.7%) with geometric mean MICs ranging from 0.030 µg/ml for C. parapsilosis, 0.042 µg/ml for C. albicans, 0.048 µg/ml for C. tropicalis, 0.082 µg/ml for C. guilliermondii, to 0.137 µg/ml for C. glabrata. Only 2 C. albicans (2%) were resistant to voriconazole showing cross-resistance to other azoles. Posaconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent useful alternatives for recalcitrant or recurrent candidiasis.

Prevalence and antifungal susceptibility patterns of new cryptic species inside the species complexes Candida parapsilosis and Candida glabrata among blood isolates from a Spanish tertiary hospital.

OBJECTIVES: There is scarce information on the clinical relevance and antifungal susceptibility of Candida bracarensis, Candida nivariensis, Candida orthopsilosis and Candida metapsilosis. The objective of this study was to assess the prevalence and in vitro antifungal susceptibility of these cryptic species among 173 blood isolates previously identified as Candida glabrata or Candida parapsilosis at the Hospital of Cruces (Barakaldo, Spain). The survey was extended to 518 clinical isolates from the culture collection of the Universidad del País Vasco-Euskal Herriko Unibertsitatea (UPV-EHU; Bilbao, Spain). METHODS: In vitro susceptibilities to 5-fluorocytosine, amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, micafungin, posaconazole and voriconazole were tested. RESULTS: All isolates of C. glabrata were identified as C. glabrata sensu stricto. Inside the C. parapsilosis complex, 2.4% of isolates from the Hospital of Cruces and 5.8% from the UPV-EHU were C. metapsilosis or C. orthopsilosis. Of 457 isolates, 435 (95.19%) were C. parapsilosis sensu stricto, 11 (2.41%) C. metapsilosis and 11 (2.41%) C. orthopsilosis. Only seven blood isolates were C. metapsilosis (0.44%) or C. orthopsilosis (1.09%). These cryptic species were also isolated from other relevant clinical specimens. Four C. parapsilosis sensu stricto (5.6%) were susceptible dose-dependent, and one was resistant to both fluconazole and voriconazole (1.4%). Moreover, 19 isolates of C. parapsilosis sensu stricto (26.4%) were intermediately susceptible to itraconazole and higher concentrations of echinocandins were needed to inhibit this species. Most C. orthopsilosis and C. metapsilosis were susceptible to all antifungal agents tested, but one otic isolate of C. metapsilosis was resistant to fluconazole and 5-fluorocytosine. CONCLUSIONS: C. metapsilosis and C. orthopsilosis are associated with human disease and show a different antifungal susceptibility profile compared with C. parapsilosis sensu stricto.

In vitro activity of voriconazole against Mexican oral yeast isolates.

Oral candidiasis is the most prevalent complication in HIV-infected and AIDS patients. Topical antifungal treatment is useful for the initial episodes of oral candidiasis, but most patients suffer more than one episode and fluconazole or itraconazole can help in the management, and voriconazole may represent a useful alternative agent for the treatment of recalcitrant oral and oesophageal candidiasis. The aim of this research was to study the in vitro activity of voriconazole and fluconazole against Mexican oral isolates of clinically relevant yeast. The in vitro susceptibility of 187 oral yeast isolates from HIV-infected and healthy Mexicans was determined for fluconazole and voriconazole by the M44-A disc diffusion method. At 24 h, fluconazole was active against 179 of 187 isolates (95.7 %). Moreover, a 100% susceptibility to voriconazole was observed. Voriconazole and fluconazole are highly active in vitro against oral yeast isolates. This study provides baseline data on susceptibilities to both antifungal agents in Mexico.

[Antifungal agents for onychomycoses]. / Antifúngicos disponibles para el tratamiento de las micosis ungueales.

Nail fungal infections are considered one of the major dermatological problems due to their high rate of therapeutic failure, management and treatment difficulties. Long-term treatments, inadequate therapies, mycological misdiagnosis and follow-up, secondary alterations of the nail, and resistant microorganisms, are some of the causes of these complications. Although the discovery of new antifungal agents has provided some effective molecules, none of the current available drugs are totally effective. It is important to continue researching in this field to provide new antifungal agents and combined therapies.

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.

Comparative evaluation of ATB Fungus 2 and Sensititre YeastOne panels for testing in vitro Candida antifungal susceptibility.

ATB Fungus 2 and SensititreYeastOne are commercial methods for antifungal susceptibility testing of yeasts. The agreement between these two methods was assessed with a total of 133 Candida strains (60 Candida albicans, 18 Candida dubliniensis, 29 Candida glabrata, and 26 Candida krusei). MIC endpoints were established after 24 h of incubation at 36-/+1 degrees C by each method. Intra-laboratory reproducibility of both methods was excellent (=or>99%). Overall agreement between ATB Fungus 2 and Sensititre YeastOne 3 MICs (within 2 dilutions) was 91.2-97.7% for amphotericin B, 5-fluorocytosine and itraconazole, and 82.7% for fluconazole. The categorical agreement when ATB Fungus 2 results were compared to those by SensititreYeastOne 3 was 93.2-98.5% for 5-fluorocytosine and amphotericin B, but lower for the triazoles (72.9-75.9%). This easy to perform method could be an alternative for routine use in the clinical microbiology laboratory for susceptibility testing of common Candida spp.

[In vitro antifungal activity of voriconazole: New data after the first years of clinical experience]. / Actividad antifúngica in vitro de voriconazol: Nuevos datos después de los primeros años de experiencia clínica.

Voriconazole has been developed to meet the increasing need for new and useful antifungal agents for the treatment of invasive mycoses. This review describes the spectrum of voriconazole antifungal activity based on data from in vitro studies published during the last three years. This survey demonstrates that voriconazole has a broad antifungal spectrum against the most common fungal pathogens being its action fungistatic for Candida and fungicidal for Aspergillus and other filamentous fungi. Overall, more than 95% of all Candida isolates tested are susceptible to voriconazole and less than 3% are resistant. Similar or even better activity rates have been described for Aspergillus, Cryptococcus and most of yeasts and moulds of medical importance. We also discuss the limitations related to the azole cross-resistance observed in some Candida glabrata isolates, the poor activity of voriconazole against Scedosporium prolificans, its activity against fungal biofilms and the great potential usefulness of combination of voriconazole with other antifungal drugs.

[In vitro antifungal activity of voriconazole against dermatophytes and superficial isolates of Scopulariopsis brevicaulis]. / Actividad antifúngica in vitro de voriconazol contra dermatofitos y aislamientos superficiales de Scopulariopsis brevicaulis.

We have studied the in vitro antifungal activity of voriconazole, fluconazole and itraconazole against 252 clinical isolates of dermatophytes and Scopulariopsis brevicaulis by a standardized agar diffusion method (NeoSensitabs). Several important factors such as temperature (28 degrees C vs. 35 degrees C) and incubation time (2-10 days vs. 18-74 h) were adapted to dermatophytes and Scopulariopsis requirements. Voriconazole showed an excellent activity against most species of dermatophytes, higher than itraconazole and fluconazole. However, S. brevicaulis isolates were highly resistant to all azoles used in this study. Voriconazole might be an interesting antifungal alternative to refractory superficial mycoses.

[In vitro antifungal susceptibility profile of Scopulariopsis brevicaulis isolated from onychomycosis]. / Perfil de sensibilidad antifúngica in vitro de Scopulariopsis brevicaulis aislados de onicomicosis.

We studied the in vitro antifungal activity profile of amorolfine (AMR), bifonazole (BFZ), clotrimazole (CLZ), econazole (ECZ), fluconazole (FNZ), itraconazole (ITZ), ketoconazole (KTZ), miconazole (MNZ), oxiconazole (OXZ), tioconazole (TCZ) and terbinafine (TRB) against 26 clinical isolates of Scopulariopsis brevicaulis from patients with onychomycosis by means of an standardized microdilution method. Although this opportunistic filamentous fungi was reported as resistant to several broad-spectrum antifungals agents, obtained data shows a better fungistatic in vitro activity of AMR, OXZ and TRB (0.08, 0.3, and 0.35 mg/L, respectively) in comparison to that of CLZ (0.47 mg/L), ECZ (1.48 mg/L), MNZ (1.56 mg/L, BFZ (2.8 mg/L), TCZ (3.33 mg/L), KTZ (3.73 mg/L). FNZ (178.47 mg/L) and ITZ (4.7 mg/L) showed a reduced in vitro antifungal activity against S. brevicaulis. Obtained MICs show the low in vitro antifungal susceptibility of S. brevicaulis to topical drugs for onychomycosis management, with exceptions (AMR, OZX and TRB).

[Clinical usefulness of triazole derivatives in the management of fungal infections]. / La utilidad clínica de los derivados triazólicos en el tratamiento de las infecciones fúngicas.

Current therapy for mycoses is limited to the use of a relative reduced number of antifungal drugs. Although amphotericin B still remains considered as the "gold standard" for treatment, acute and chronic toxicity, such as impairment of renal function, limits its use and enhances the investigation and clinical use other chemical families of antifungal drugs. One of these chemical class of active drugs are azole derivatives, discovered in 70s and introduced in clinical practice in 80s. Being the most prolific antifungal class, investigation about more molecules, with a safer and better pharmacological profile, active against a wide spectrum of fungi, with a wide range of administration routes gives us some azole representatives.

[Evaluation of the in vitro susceptibility pattern of clinical isolates of Trichophyton mentagrophytes and Trichophyton rubrum in Santiago, Chile]. / Evaluación del perfil de sensibilidad in vitro de aislamientos clínicos de Trichophyton mentagrophytes y Trichophyton rubrum en Santiago, Chile.

BACKGROUND: Dermatophytes are a group of keratinophilic fungi able to produce dermatophytosis or tinea infections. In Chile, Trichophyton rubrum and Trichophyton mentagrophytes are the ones most commonly isolated in adults, while Microsporum canis is found among children. Treatment of these infections is usually with topical or oral antifungals, such as griseofulvin or azole derivatives (clotrimazole, itraconazole, fluconazole), allylamines (terbinafine) or new drugs that are available. AIMS: Evaluation of the in vitro susceptibility of dermatophytes to five antifungal agents and the comparison of the susceptibility pattern with that of previous years. METHODS: Sixty-two clinical isolates of dermatophyte fungi were studied (March-June 2010). The CLSI M38-A2 micromethod was used. RESULTS: Fluconazole MIC values for T. rubrum and T. mentagrophytes varied between 0.25 and 1 µg/ml; MIC range to clotrimazole, terbinafine and itraconazole was 0.03-0.06 µg/ml, and MIC values for griseofulvin were 0.015-0.03 µg/ml. No statistically significant differences were found between susceptibility patterns, except for fluconazole. CONCLUSIONS: Fluconazole was less active in comparison with other drugs tested (0.25-1 µg/ml). None of the isolates were resistant to any of the drugs, and no changes in the susceptibility pattern were observed when comparing the results with data previously reported concerning dermatophytes in Chile.

In-vitro activity of 5-fluorocytosine against 1,021 Spanish clinical isolates of Candida and other medically important yeasts.

The aim of this study was to determine the prevalence of primary resistance to 5-fluorocytosine (5FC) among clinical isolates of yeasts in Spain where this drug is not currently available for therapy. We have tested the in vitro activity of 5FC against 1,021 recent yeast clinical isolates, including 522 Candida albicans, 140 Candida parapsilosis, 68 Candida glabrata, 41 Candida dubliniensis, 50 Candida guilliermondii, 34 Candida tropicalis, 28 Candida krusei, 20 Candida famata, 11 Cryptococcus neoformans, 5 Cryptococcus albidus, 43 Rhodotorula spp., 24 Trichosporon spp., 5 Saccharomyces cerevisiae, 9 Pichia spp., and 21 isolates from other 11 yeast species. The MICs were determined by the ATB Fungus agar microdilution test (bioMerieux, France) and the following interpretive breakpoints were used: susceptible, > 4 microg/ml; intermediate, 8 to 16 microg/ml; resistant, > 32 microg/ml. 5FC was very active against Candida spp. and other medically important yeasts as 852 (83.4%) of the studied isolates were susceptible (MIC < 4 microg/ml). The species most susceptible to 5FC were C. dubliniensis (100%of isolates; MIC90, 0.25 microg/ml), C. famata (100% of isolates; MIC90, 0.25 microg/ml), C. guilliermondii (98%of isolates; MIC90, 0.25 microg/ml), C. glabrata (95.5% of isolates; MIC90, 0.25 microg/ml), and C. neoformans (90.9% of isolates; MIC90, 2 microg/ml). Primary resistance to 5FC was very uncommon, and a MIC > 32 microg/ml, indicator of in vitro resistance, was observed in 106 isolates (10.4%): 77 C. albicans (16.5% of isolates; MIC90, > 128 microg/ml), 9 C. parapsilosis (6.4% of isolates; MIC90, 8 microg/ml), 4 C. albidus (80% of isolates, MIC50, > 128 microg/ml), 3 C. glabrata (4.4% of isolates; MIC90, 0.25 microg/ml), 3 C. tropicalis (8.8% of isolates; MIC90, 4 microg/ml), 2 C. krusei (7.1% of isolates; MIC90, 8 microg/ml), 2 Rhodotorula spp. (4.6% of isolates, MIC90, 1 microg/ml), 8 Trichosporon spp. (33.3% of isolates; MIC90, 64 microg/ml), and 1 C. lipolytica (50% of isolates). Interestingly, most C. albicans (67 out of 77 isolates) resistant to 5FC were serotype B isolates.

[Influence of the ecological group on the in vitro antifungal susceptibility of dermatophytic fungi]. / Influencia del grupo ecológico sobre la sensibilidad in vitro de los hongos dermatofitos a los antifúngicos.

BACKGROUND: Dermatophytes can be divided into geophilic (soil), zoophilic (animals) and anthropophilic (humans) strains, depending on the source of the keratin that they use for nutritional purposes. AIMS: The in vitro susceptibility of clinical isolates of dermatophyte fungi has been studied in the 3 ecological groups with several antifungal agents for the topical management of dermatophytoses in order to determine their relationship with the ecological group. METHODS: A standardised dilution micromethod in a liquid medium was used for the determination of the in vitro antifungal activity of 9 topical antifungal drugs: amorolfine (AMR), bifonazole (BFZ), clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, terbinafine (TRB) and tioconazole. The in vitro activity was obtained against 124 clinical isolates of dermatophyte moulds from the anthropophilic, zoophilic and geophilic ecological groups. RESULTS: The in vitro antifungal activity was different depending on the ecological group, although a species-dependent profile was also observed. CONCLUSIONS: Azole derivatives showed a similar antifungal profile, being more active against anthropophilic dermatophytes > zoophilic > geophilic. Activity of TRB and AMR was different from that of azole derivatives (zoophilic > anthropophilic > geophilic). A higher in vitro antifungal activity against the 3 ecological groups was observed with TRB and AMR, whilst BFZ was the less active drug.

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.

Identificación y sensibilidad antifúngica in vitro de Candida spp. de origen vaginal a fluconazol, clotrimazol y nistatina / Identification and in vitro antifungal susceptibility of vaginal Candida spp. isolates to fluconazole, clotrimazole and nystatin

Objetivo. Identificar especie y determinar la sensibilidad in vitro a clotrimazol, fluconazol y nistatina de 145 aislamientos de Candida spp. Material y métodos. Se utilizó un método de microdilución en caldo (M27-A3) para determinar la concentración inhibitoria mínima (CMI) y además las CMI50 y CMI90 de los antifúngicos. De los 145 aislamientos, 126 correspondieron a C. albicans, 16 C. glabrata, 2 C. parapsilosis y 1 C. tropicalis. Resultados. La CMI50 y CMI90 de fluconazol frente C. albicans fueron de 0,25 mg/L y 1 mg/L y para C. glabrata de 8 y 16 mg/L, respectivamente. Cinco aislados de C. albicans y un aislado de C. tropicalis fueron resistentes a fluconazol (M27- S4). Las CIM50 y CIM90 de clotrimazol frente a C. albicans fueron 0,03 mg/L y 0,06 mg/L y para C. glabrata de 0,25 mg/L y 1 mg/L, mientras que para nistatina fueron de 1 mg/L y de 2 mg/L, respectivamente para C. albicans y C. glabrata. Cinco aislados de C. glabrata y 1 de C. tropicalis fueron resistentes a clotrimazol. Conclusión. En este estudio, C. albicans es la levadura más frecuentemente aislada, seguida de C glabrata. Los antifúngicos evaluados resultaron ser activos in vitro para las cepas aisladas, excepto en 6 aislados para fluconazol y 6 para clotrimazol (AU)

Objective. The aim of this study was to identify and determine the in vitro antifungal susceptibility testing to clotrimazole, fluconazole, and nystatin of 145 clinical isolates of Candida spp. Material and methods. M27-A3 microdilution method was used to determine minimal inhibitory concentrations (MIC) and partial MICs (MIC50 and MIC90) of drugs. A total of 145 isolates were studied, 126 were C. albicans, 16 C. glabrata, 2 C. parapsilosis y 1 C. tropicalis. Results. MIC50 and MIC90 for FLZ against C. albicans were 0.25 mg/L and 1 mg/L respectively and for C. glabrata was achieved at 8 mg/L and 16 mg/L for fluconazole. Five isolates of C. albicans and one isolate of C. tropicalis were in vitro resistant to fluconazole (M27-S4). In C. albicans MIC50 and MIC90 for clotrimazole were of 0.03 mg/L and 0.06 mg/L, respectively. These values for C. glabrata were 0.25 mg/L and 1 mg/L, respectively. Five C. glabrata and 1 C. tropicalis were in vitro resistant to clotrimazole. MIC50 and MIC90 of nystatin were of 1 mg/L and 2 mg/L, respectively for C. albicans and C. glabrata. Conclusion. In this study, C. albicans is the most frequently isolated yeast, followed by C glabrata. The antifungals tested were found to be in vitro active for the isolates, except for 6 isolates for fluconazole and 6 to clotrimazole (AU)

Una nueva generación de antifúngicos para el tratamiento de las micosis superficiales / A new generation of antifungals for the treatment of dermatomycosis

Las infecciones fúngicas superficiales responden bien a los tratamientos habituales en la mayoría de los casos pero, en determinadas situaciones, constituyen un problema. En su mayoría se trata de infecciones producidas por levaduras del género Candida y Malassezia y por hongos dermatofitos. Estas infecciones han visto incrementada su prevalencia junto con la selección de determinadas especies, la reducción de la sensibilidad a los antifúngicos y la aparición de fenómenos de resistencia in vitro e in vivo. La investigación para encontrar el antifúngico ideal aún continúa y en este sentido actualmente se están ensayando distintas estrategias de investigación sobre drogas para el tratamiento sistémico y tópico de las dermatomicosis.

Superficial fungal infections frequently caused by Candida spp. and Malassezia spp yeasts and dermatophytes fungi, have good response to common treatments in the majority of cases, but in some cases failure are described. Prevalence of these infections has been increased with the selection of certain species, reduced sensitivity to antifungal agents and the emergence of in vitro and in vivo resistance phenomena. The research to find the ideal antifungal still continues and in this sense are being currently tested different strategies for research on systemic and topical drugs for dermatomycosis treatment.

La utilidad clínica de los derivados triazólicos en el tratamiento de las infecciones fúngicas / Clinical usefulness of triazole derivatives in the management of fungal infections

El tratamiento de las infecciones producidas por hongos se limita al uso de un reducido número de moléculas. Si bien, la anfotericina B aún sigue siendo considerada como el antifúngico de referencia, para el tratamiento de estas infecciones, la toxicidad aguda y crónica que produce así como el fallo renal limitan su uso y de alguna manera supuso un empuje a la investigación de nuevas familias de sustancias que pudieran ser empleadas en clínica. Una de esas familias es la de los derivados azólicos, descubierta en la década de los años 70 que fue introducida en la práctica clínica en la década posterior. Aun siendo la familia de antifúngicos más prolífica, la investigación sobre nuevas moléculas más seguras y con un mejor perfil farmacológico a la vez que presenten una mayor actividad frente a un amplio espectro de hongos patógenos y con la mayor cantidad rutas de administración (AU)

Current therapy for mycoses is limited to the use of a relative reduced number of antifungal drugs. Although amphotericin B still remains considered as the “gold standard” for treatment, acute and chronic toxicity, such as impairment of renal function, limits its use and enhances the investigation and clinical use other chemical families of antifungal drugs. One of these chemical class of active drugs are azole derivatives, discovered in 70s and introduced in clinical practice in 80s. Being the most prolific antifungal class, investigation about more molecules, with a safer and better pharmacological profile, active against a wide spectrum of fungi, with a wide range of administration routes gives us some azole representatives (AU)

Perfil de sensibilidad antifúngica in vitro de Scopulariopsis brevicaulis aislados de onicomicosis / In vitro antifungal susceptibility profile of Scopulariopsis brevicaulis isolated from onychomycosis

Se ha estudiado el perfil de actividad antifúngica in vitro de amorolfina (AMR), bifonazol (BFZ), clotrimazol (CLZ), econazol (ECZ), fluconazol (FNZ), itraconazol (ITZ), ketoconazol (KTZ), miconazol (MNZ), oxiconazol (OXZ), tioconazol (TCZ) y terbinafina (TRB) frente a 26 aislamientos clínicos de Scopulariopsis brevicaulis obtenidos de muestras clínicas de pacientes con onicomicosis, por medio de un método estandarizado de microdilución. A pesar de que este hongo filamentoso ha sido descrito como resistente frente a un amplio espectro de antifúngicos, los datos obtenidos muestran una mejor actividad fungistática in vitro de AMR, OXZ y TRB (0,08; 0,3 y 0,35 mg/L, respectivamente) en comparación con la de CLZ (0,47 mg/L), ECZ (1,48 mg/L), MNZ (1,56 mg/L, BFZ (2,8 mg/L), TCZ (3,33 mg/L), KTZ (3,73 mg/L). FNZ (178,47 mg/L) e ITZ (4,7 mg/L) mostraron una reducida actividad antifúngica in vitro. Las CMIs obtenidas muestran la reducida sensibilidad in vitro en general de S. brevicaulis a los antifúngicos utilizados y que son de posible uso para el tratamiento de las onicomicosis con la excepción de AMR, OXZ y TRB (AU9

We studied the in vitro antifungal activity profile of amorolfine (AMR), bifonazole (BFZ), clotrimazole (CLZ), econazole (ECZ), fluconazole (FNZ), itraconazole (ITZ), ketoconazole (KTZ), miconazole (MNZ), oxiconazole (OXZ), tioconazole (TCZ) and terbinafine (TRB) against 26 clinical isolates of Scopulariopsis brevicaulis from patients with onychomycosis by means of an standardized microdilution method. Although this opportunistic filamentous fungi was reported as resistant to several broad-spectrum antifungals agents, obtained data shows a better fungistatic in vitro activity of AMR, OXZ and TRB (0.08, 0.3, and 0.35 mg/L, respectively) in comparison to that of CLZ (0.47 mg/L), ECZ (1.48 mg/L), MNZ (1.56 mg/L, BFZ (2.8 mg/L), TCZ (3.33 mg/L), KTZ (3.73 mg/L). FNZ (178.47 mg/L) and ITZ (4.7 mg/L) showed a reduced in vitro antifungal activity against S. brevicaulis. Obtained MICs show the low in vitro antifungal susceptibility of S. brevicaulis to topical drugs for onychomycosis management, with exceptions (AMR, OZX and TRB) (AU)

Evaluación del perfil de sensibilidad in vitro de aislamientos clínicos deTrichophyton mentagrophytes y Trichophyton rubrum en Santiago, Chile / Evaluation of the in vitro susceptibility pattern of clinical isolates of Trichophyton mentagrophytes and Trichophyton rubrum in Santiago, Chile

Antecedentes: Los dermatofitos son un grupo de hongos queratinolíticos que producen infecciones denominadas dermatofitosis o tiñas. En Chile, los dermatofitos aislados con mayor frecuencia son Trichophyton rubrumy Trichophyton mentagrophytes en la población adulta, y Microsporum canis en niños prepúberes. Para el tratamiento de estas micosis se emplean antifúngicos tópicos y orales como la griseofulvina, antifúngicos azólicos como el clotrimazol, el itraconazol o el fluconazol, alilaminas como la terbinafina, y nuevas moléculas antifúngicas. Objetivos: Evaluar la sensibilidad in vitro de los dermatofitos frente a cinco antifúngicos y establecer posibles cambios respecto a estudios anteriores. Métodos: Se estudiaron 62 dermatofitos obtenidos de muestras clínicas (marzo-junio de 2010). Se utilizó el método de microdilución en caldo (M38-A2). Resultados: El rango de CMI para el fluconazol fue de 0,25-1 μg/ml; 0,03-0,06 μg/ml para el clotrimazol, la terbinafina y el itraconazol, y 0,015-0,03 μg/ml para la griseofulvina frente a T. rubrum y T. mentagrophytes. Excepto para le fluconazol, no se encontraron diferencias estadísticas significativas en los rangos de sensibilidad antifúngica. Conclusiones: Los valores de CMI para el fluconazol fueron los más altos (0,25-1 μg/ml) de todas las sustancias ensayadas, habiendo diferencias estadísticamente significativas entre este y el resto de antifúngicos. No hubo cepas resistentes a los antifúngicos analizados, y tampoco se encontraron cambios en el perfil de sensibilidad antifúngica in vitro en relación con estudios anteriores realizados en Chile (AU)

Background: Dermatophytes are a group of keratinophilic fungi able to produce dermatophytosis or tinea infections. In Chile, Trichophyton rubrum and Trichophyton mentagrophytes are the ones most commonly isolated in adults, while Microsporum canis is found among children. Treatment of these infections is usually with topical or oral antifungals, such as griseofulvin or azole derivatives (clotrimazole, itraconazole, fluconazole), allylamines (terbinafine) or new drugs that are available. Aims: Evaluation of the in vitro susceptibility of dermatophytes to five antifungal agents and the comparison of the susceptibility pattern with that of previous years. Methods: Sixty-two clinical isolates of dermatophyte fungi were studied (March-June 2010). The CLSI M38-A2 micromethod was used. Results: Fluconazole MIC values for T. rubrum and T. mentagrophytes varied between 0.25 and 1 μg/ml; MIC range to clotrimazole, terbinafine and itraconazole was 0.03-0.06 μg/ml, and MIC values for griseofulvin were 0.015-0.03 μg/ml. No statistically significant differences were found between susceptibility patterns, except for fluconazole. Conclusions: Fluconazole was less active in comparison with other drugs tested (0.25-1 μg/ml). None of the isolates were resistant to any of the drugs, and no changes in the susceptibility pattern were observed when comparing the results with data previously reported concerning dermatophytes in Chile (AU)