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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.

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).

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., (Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Aim: To analyse the safety and effectiveness of natalizumab in the treatment of multiple sclerosis in a real clinical practice setting and according to the approved indications., Patients and Methods: All patients with multiple sclerosis treated with natalizumab in our centre were evaluated. The clinical and radiological disease activity during the first year of treatment was analyzed in patients who received at least 12 doses of the drug. The data regarding moderate and severe adverse events in the entire study sample was also evaluated., Results: A total of 112 patients were included in the study, of which 110 had been previously treated with other drugs and 76 had received at least 12 doses of natalizumab. In this group, the annualized relapse rate was reduced by 89% compared to the preceding year and 80% of patients were free from relapses after one year of treatment. Nine percent of patients exhibited 3-month confirmed disability progression. At month 12, the mean number of gadolinium-enhancing lesions on brain MRI was decreased by 99% compared to the pre-treatment MRI. During the first year of treatment, 76% of patients remained free from clinical activity and 33% remained free from both clinical and radiological disease activity. Twenty-nine percent of patients had at least one moderate or severe adverse event, which led to treatment discontinuation in 6%. Four percent of patients experienced immediate hypersensitivity reactions., Conclusion: This study suggests that natalizumab is effective in reducing disease activity in patients with relapsing multiple sclerosis and inadequate response to other therapies, with a favorable risk-benefit ratio.

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., (Copyright 2009 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Acute disseminated encephalomyelitis (ADEM) is an uncommon disease characterized by inflammation and demyelination of the central nervous system (CNS). It typically occurs after a viral infection or vaccination and is more frequent in children. Its immediate and longterm prognosis is expected to be good (20% of cases with sequelae). Although ADEM is typically monophasic, occasional relapses may occur. Differential diagnosis, mostly in the early phases, is established with multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS that may have worse prognosis. Traditionally it has been believed that 10% of ADEM patients develop MS. However, this percentage could be higher according to several recently published clinical series. Some clinical and paraclinical patterns are considered to confer risk of developing MS when present in ADEM patients. Our study has aimed to: a) describe a series of 29 patients (22 children and 9 adults) admitted in our hospital and diagnosed of ADEM between 1990 and 2005; b) study those patients considered to have risk patterns of developing MS, and c) compare the child and adult populations of our series. After a median 55 month follow-up, 6 children (27%) and no adults developed MS. In our series, risk patterns for developing MS predicted conversion to MS more accurately in children than in adults. Eight patients (6 children and 2 adults) had sequelae, cognitive in 6 of them. Our work supports that also observed in recent publications: that both conversion to MS or presence of sequelae after an episode of ADEM are more frequent than traditionally considered.

Using Sensititre (AccuMed, USA) we studied the in vitro antifungal activity of amphotericin B, fluconazole, itraconazole, ketoconazole and 5-fluorocytosine against 250 clinical yeast isolates taken from different hospitals, including Candida (151 C. albicans, 15 C. krusei, 14 C. parapsilosis, 11 C. tropicalis, 10 C. glabrata, 4 C. guilliermondii, 3 C. rugosa, 2 C. viswanathii, 2 C. famata and 2 C. kefyr), Cryptococcus (32 C. neoformans and 1 C. laurentii), Trichosporon (2 isolates) and Rhodotorula rubra (1 isolate). All the strains were susceptible to amphotericin B and showed an MIC <1 mg/l. The susceptibility of C. albicans (MIC(90) <256 mg/l), C. krusei (MIC(90) <64 mg/l), C. glabrata (MIC(90) <64 mg/l) and C. neoformans (MIC(90) 32 mg/l) to fluconazole was lower (14% isolates being resistant and 16.8% susceptible depending on the dose). The largest number of strains resistant to itraconazole was observed in C. albicans and C. glabrata (17.2% resistant and 24% susceptible and susceptible depending on the dose, respectively). Ketoconazole and 5-fluorocytosine were not effective in vitro against 12.8% and 2%, respectively, of all the isolates studied. Nine C. krusei and seven C. neoformans (12.9%) showed dose-dependent susceptibility to 5-fluorocytosine.

We evaluated a commercial method for studying the in vitro susceptibility to sertaconazole based on its diffusion in agar with standardized tablets, with the aim of determining its correlation with the method of microdilution in Shadomy modified liquid medium (YNBg). A total of 110 Candida genus strains (50 C. albicans, 26 C. tropicalis, 15 C. glabrata, 8 C. parapsilosis, 8 C. krusei, 2 C. guilliermondii and 1 C. kefyr) from pathological clinical processes were used. The results of both techniques showed a statistically significant correlation that depended on the type of reading used in the liquid medium microdilution technique, with results being -0. 4199 with IC50; -5135 with IC90: -0.6634 with MIC24 h; and -0.4945 with MIC48 h. These values demonstrate the existence of a correlation for sertaconazole, and that it is bigger when it is compared with the logarithm of the MIC obtained after 24 hours of incubation.

An in vitro susceptibility testing of 181 strains of six species of Candida and 21 strains of Cryptococcus neoformans was carried out in order to investigate the resistance to new antifungal drugs. We have studied clinical isolates from 200 different patients of Hospital del Mar (Barcelona) and Hospital La Inmaculada (Almería). An agar diffusion method (NeoSensitabs, Rosco, Taastrup, Denmark), was employed with fluconazole, itraconazole, and reference drugs amphotericin B, flucytosine, tioconazole and ketoconazole. A high level of susceptibility was found for amphotericin B in C. neoformans strains while 19% of them were resistant to flucytosine. All the strains of C. neoformans and Candida guilliermondii were susceptible to the new azoles derivatives and also Candida parapsilosis and Candida albicans had a great susceptibility to this antifungals. A greater level of resistance was found for Candida krusei, Candida tropicalis and Candida glabrata to fluconazole, itraconazole and ketoconazole, but resistance to fluconazole and itraconazole is not always linked because ten resistant strains for fluconazole were susceptible to itraconazole, and two other resistant to itraconazole were susceptible to fluconazole.