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The aims of this study were to characterize the antifungal activity of amphotericin B against Candida auris in a static in vitro system and to evaluate different dosing schedules and MIC scenarios by means of semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modelling and simulation. A two-compartment model consisting of a drug-susceptible and a drug-resistant subpopulation successfully characterized the time-kill data and a modified E(max) sigmoidal model best described the effect of the drug. The model incorporated growth rate constants for both subpopulations, a death rate constant and a transfer constant between both compartments. Additionally, the model included a parameter to account for the delay in growth in the absence or presence of the drug. Amphotericin B displayed a concentration-dependent fungicidal activity. The developed PK/PD model was able to characterize properly the antifungal activity of amphotericin B against C. auris. Finally, simulation analysis revealed that none of the simulated standard dosing scenarios of 0.6, 1 and 1.5 mg/kg/day over a week treatment showed successful activity against C. auris infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for C. auris invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.

The pathogen Candida auris is rapidly gaining clinical importance because of its resistance to antifungal treatments and its persistence in hospital environments. Early and accurate diagnosis of C. auris infections is crucial, however, the fungus has often been misidentified by commercial systems.

Anidulafungin, caspofungin, and micafungin killing activities against Candida glabrata, Candida bracarensis, and Candida nivariensis were evaluated by the time-kill methodology. The concentrations assayed were 0.06, 0.125, and 0.5 mu g/ml, which are achieved in serum. Anidulafungin and micafungin required between 13 and 26 h to reach the fungicidal endpoint (99.9% killing) against C. glabrata and C. bracarensis. All echinocandins were less active against C. nivariensis.

Candida albicans remains the most common fungal pathogen. This species is closely related to 2 phenotypically similar cryptic species. Candida dubliniensis and Candida africana. This study aims to compare the antifungal activities of echinocandins against 7 Candida albicans, 5 Candida dubliniensis, and 2 Candida africana strains by time-kill methodology. MIC values were similar for the 3 species; however, differences in killing activity were observed among species, isolates, and echinocandins. Echinocandins produced weak killing activity against the 3 species. In all drugs, the fungicidal endpoint (99.9% mortality) was reached at = 0.5 mu g/mL for anidulafungin in 4 Candida albicans and 1 Candida dubliniensis, for caspofungin in 1 Candida albicans and 2 Candida dubliniensis, and for micafungin in 4 Candida albicans and 1 Candida dubliniensis. None of echinocandins showed lethality against Candida africana. Identification of these new cryptic species and time-kill studies would be recommendable when echinocandin treatment fails. (C) 2015 Elsevier Inc. All rights reserved.

The lack of an ideal antifungal drug or completely successful agent, suggests that combination therapy may be an appropriate option for the management of fungal infections. In this review, different antifungal combination therapy approaches will be discussed. In brief, the rationale for combination therapy is to maximize antifungal effects by attacking different fungal targets at the same time. However, the scientific basis for this approach requires evidence from prospective clinical trials of antifungal combinations. It is possible that real advantages will be seen for particular combinations only in particular mycoses and/or particular types of patient. Combination tends to reduce clinical failure when resistant strains could be recovered from patients, although drug interactions and cross-resistance may result. Synergy has been established between conventional antifungal agents and also between investigational molecules. Alternatively, combination of fluconazole and cyclosporine results fungicidal for fluconazole-susceptible strains of Candida albicans. An overall enhanced susceptibility is reached in intrinsically resistant Candida when combination of azole antifungal drugs or terbinafine with calcineurin inhibitors is used. Azoles, such as voriconazole, itraconazole, and fluconazole are being tested in combination with other antifungal agents such as amphotericin B, caspofungin, or terbinafine and. In addition, amphotericin B is actually administered in combined therapy with caspofungin. The traditional combinations of amphotericin B plus 5-fluorocytosine or amphotericin B plus rifampicin have been replaced by these newer combinations. Other combinations such as caspofungin plus amphotericin B or voriconazole have also been synergic against clinical isolates of Aspergillus and Fusarium. This has been confirmed in animal models in the case of caspofungin plus itraconazole in the treatment of invasive pulmonary aspergillosis and caspofungin plus liposomal amphotericin B in the management of invasive aspergillosis. Fil: Carrillo Muñoz, A. J.. Departamento de Micología; España Fil: Finquelievich, Jorge. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Tur Tur, Cristina. Departamento de Micología; España Fil: Eraso, Elena. Universidad del Pais Vasco; España Fil: Jaureguizar, Nerea. Universidad del Pais Vasco; España Fil: Quindós, Guillermo. Universidad del Pais Vasco; España Fil: Giusiano, Gustavo Emilio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

To update the knowledge of the epidemiology of fungaemia episodes in Spain, the species implicated and their in vitro antifungal susceptibilities. Episodes were identified prospectively over 13 months at 44 hospitals. Molecular methods were used to determine the cryptic species inside the Candida parapsilosis and Candida glabrata complexes. Susceptibility to amphotericin B, anidulafungin, caspofungin, fluconazole, flucytosine, itraconazole, micafungin, posaconazole and voriconazole was determined by a microdilution colorimetric method. New species-specific clinical breakpoints (SSCBPs) for echinocandins, fluconazole and voriconazole were applied. The incidence of the 1357 fungaemia episodes evaluated was 0.92 per 1000 admissions. The incidence of Candida albicans fungaemia was the highest (0.41 episodes/1000 admissions), followed by Candida parapsilosis sensu stricto (0.22). Candida orthopsilosis was the fifth cause of fungaemia (0.02), outnumbered by Candida glabrata and Candida tropicalis. Interestingly, the incidence of fungaemia by C. parapsilosis was 11 and 74 times higher than that by C. orthopsilosis and Candida metapsilosis, respectively. Neither Candida nivariensis nor Candida bracarensis was isolated. Fungaemia was more common in non-intensive care unit settings (65.2) and among elderly patients (46.4), mixed fungaemia being incidental (1.5). Overall susceptibility rates were 77.6 for itraconazole, 91.9 for fluconazole and 96.599.8 for the other agents. Important resistance rates were only observed in C. glabrata for itraconazole (24.1) and posaconazole (14.5), and in Candida krusei for itraconazole (81.5). Fungaemia is more common in non-critical patients. C. albicans is the most common species, followed by C. parapsilosis and C. glabrata. Nearly 90 of yeasts are susceptible to all antifungal agents tested. Resistance rates change moderately when applying the new SSCBPs.

The evolution of both specific and nonspecific IgE in a long-term follow-up after surgery in patients with human hydatid disease was studied. Enzyme immunoassays using cyanogen bromide-activated cellulose discs as solid phase were employed. One hundred and nine postoperative serum samples from 26 patients undergoing surgery for hydatid disease were studied. Imaging studies were also carried out during the follow-up. In 8 of 26 patients, remaining cysts were detected during the follow-up. One year after surgery, total IgE levels decreased to normal values in 84.6% of the total number of patients, in 94.5% of the cases in which no remaining cysts were detected, and in 62.5% of the patients with remaining hydatid cysts. These data highlight the poor value of an isolated postoperative IgE determination as a diagnostic marker for remaining hydatidosis. On the contrary, 1 year after surgery, the levels of anti-Echinococcus IgE decreased in 55% of the patients without residual cysts and in 50% of the total number of patients. In six patients without remaining hydatid cysts, the levels of specific IgE increased 1 year after the surgery. In the group of patients with remaining cysts only in three patients did the values of specific IgE decrease, although they remained significant. Thus, 1 year after surgery, anti-Echinococcus IgE levels were still evident in all patients, although in those without remaining cysts there was a predominance of decreasing values.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, the conditions for the successful application of the random amplified polymorphic DNA (RAPD) assay to differentiate mite populations based on genetic variation were defined. Five species of mites related to allergic diseases were studied: Dermatophagoides pteronyssinus, D. farinae (2 strains), Blomia tropical is, Glycyphagus domesticus and Tyrophagus putrescentiae. The mites were isolated from pure cultures and processed according to the method described in this paper. The banding patterns obtained were different for all the species studied. When the DNA from two different strains of D. farinae were studied, the "fingerprint" banding patterns obtained showed differences between them. The random amplified polymorphic DNA assay may be a useful tool to aid the taxonomic study of mite populations.