Search

In vitro combination of echinocandins and isavuconazole against the emerging species Candida auris is mainly synergistic. However, this combination has not been evaluated in clinical settings. A pharmacokinetic/pharmacodynamic modeling and simulation approach based on in vitro data may be helpful to further study the therapeutic potential of these combinations. Therefore, the aims of this study were to characterize the time course of growth and killing of C. auris in response to the combination of the three approved echinocandins and isavuconazole using a semimechanistic model and to perform model-based simulations in order to predict the in vivo response to combination therapy. In vitro static time-kill curve data for isavuconazole and echinocandins combinations against six blood isolates of C. auris were best modeled considering the total killing of the fungal population as dependent on the additive effects of both drugs. Once assessed, the predictive performance of the model using simulations of different dosing and fungal susceptibility scenarios were conducted. Model-based simulations revealed that none of the combinations at standard or higher dosages would be effective against the studied isolates of C. auris and it was predicted that the combinations of isavuconazole with anidulafungin or caspofungin would be effective for minimum inhibitory concentrations up to 0.03 and 0.06 mg/L respectively, whereas the combination with micafungin would lead to treatment failure. The current approach highlights the importance of bridging the in vitro results to the clinic., (© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis., Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida ., Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans , 108 Candida parapsilosis , 60 Candida glabrata , 40 Candida tropicalis , 29 Candida krusei , 20 Candida orthopsilosis , 6 Candida guilliermondii , 2 Candida famata , 2 Candida lusitaniae , and 1 isolate each of Candida bracarensis, Candida catenulata , Candida dubliniensis , and Candida kefyr . MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated., Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC 50 s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans , 0.5/0.5 for C. parapsilosis , 0.25/0.25 for C. glabrata , 0.5/0.5 for C. tropicalis , 1/1 for C. krusei , 4/2 for C. orthopsilosis , and 0.5/0.5 for C. auris . Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis , 4 (5%) C. glabrata , and 1 (2.5%) C. tropicalis ., Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida ., Competing Interests: Outside the current study, we declare the following potential conflicts: GQ has received research grants from Astellas Pharma, Pfizer, Merck Sharp & Dohme, and SCYNEXIS. GQ has served on advisory/consultant boards for Merck, Sharp & Dohme, and SCYNEXIS, and he has received speaker honoraria from Abbvie, Astellas Pharma, Merck Sharp & Dohme, Pfizer, and SCYNEXIS. KB-E and DA are employed by SCYNEXIS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quindós, Miranda-Cadena, San-Millán, Borroto-Esoda, Cantón, Linares-Sicilia, Hamprecht, Montesinos, Tortorano, Prigitano, Vidal-García, Marcos-Arias, Guridi, Sanchez-Reus, Machuca-Bárcena, Rodríguez-Iglesias, Martín-Mazuelos, Castro-Méndez, López-Soria, Ruiz-Gaitán, Fernandez-Rivero, Lorenzo, Capilla, Rezusta, Pemán, Guarro, Pereira, Pais, Romeo, Ezpeleta, Jauregizar, Angulo and Eraso.)

Oral candidiasis is frequently associated with Candida biofilms. Biofilms are microbial communities related to persistent, recalcitrant and difficult to-treat infections. Conventional treatments are not sufficient to overcome biofilm-associated candidiasis; thus, the search of new antifungal compounds is necessary. In the current study, we have evaluated the effect of three phytocompounds, carvacrol, cinnamaldehyde and thymol, against Candida planktonic and sessile cells. Reduction in biofilm biomass and metabolic activity was assessed during adhesion and mature biofilm phases. Candida albicans was the most biofilm-producing Candida species. All phytocompounds tested were fungicidal against Candida planktonic cells. Cinnamaldehyde was the most active in inhibiting biofilm adhesion, but carvacrol and thymol significantly reduced both mature biofilm biomass and metabolic activity. These results highlight the role of cinnamaldehyde, carvacrol and thymol as promising alternatives for the treatment of candidiasis due to their antibiofilm capacities, and stress the necessity to continue studies on their safety, toxicity and pharmacodynamics and pharmacokinetics., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Candida albicans remains the most common aetiology of invasive candidiasis, leading to high morbidity and mortality. Nevertheless, the incidence of candidiasis due to non-C. albicans species, such as Candida parapsilosis, is increasing. Postantifungal effect (PAFE) is relevant for establishing dosage schedules in antifungal therapy, as the frequency of antifungal administration could change depending on PAFE. The aim of this study was to evaluate the PAFE of anidulafungin against C. albicans, Candida dubliniensis, Candida africana, C. parapsilosis, Candida metapsilosis and Candida orthopsilosis., Methods: Twenty-one Candida strains were evaluated. Cells were exposed to anidulafungin for 1 h at concentrations ranging from 0.12 to 8 mg/L for PAFE studies. Time-kill experiments (TK) were conducted at the same concentrations. The experiments were performed using an inoculum of 1-5 x 105 cells/mL and 48 h incubation. Readings of PAFE and TK were done at 0, 2, 4, 6, 24 and 48 h., Results: Anidulafungin was fungicidal against 2 out of 14 (14%) strains of C. albicans related species in PAFE experiments. Moreover, 2 mg/L of anidulafungin exerted a prolonged PAFE (≥ 33.6 h) against 13 out of 14 (93%) strains. Similarly, fungicidal endpoint was achieved against 1 out of 7 (14%) strains of C. parapsilosis complex, being PAFE prolonged (≥ 42 h) against 6 out of 7 (86%) strains., Conclusions: Anidulafungin induced a significant and prolonged PAFE against C. albicans and C. parapsilosis and their related species., (©The Author 2019. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation., Material and Methods: Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library., Results: Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides., Conclusions: Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.

Background: Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis are emerging as relevant causes of candidemia. Moreover, they show differences in their antifungal susceptibility and virulence. The echinocandins are different in terms of in vitro antifungal activity against Candida. Time-kill (TK) curves represent an excellent approach to evaluate the fungicidal activity of antifungal drugs., Aims: To compare the fungicidal activities of anidulafungin, caspofungin and micafungin against C. parapsilosis species complex by TK curves., Methods: Antifungal activities of three echinocandins against C. parapsilosis, C. metapsilosis and C. orthopsilosis were studied by TK curves. Drug concentrations assayed were 0.25, 2 and 8μg/ml. CFU/ml were determined at 0, 2, 4, 6, 24 and 48h., Results: Killing activities of echinocandins were species-, isolates- and concentration-dependent. Anidulafungin reached the fungicidad endpoint for 6 out of 7 isolates (86%); it required between 13.34 and 29.67h to reach this endpoint for the three species studied, but more than 48h were needed against one isolate of C. orthopsilosis (8μg/ml). Caspofungin fungicidal endpoint was only achieved with 8μg/ml against one isolate of C. metapsilosis after 30.12h (1 out of 7 isolates; 14%). Micafungin fungicidal endpoint was reached in 12.74-28.38h (8μg/ml) against one isolate each of C. parapsilosis and C. orthopsilosis, and against both C. metapsilosis isolates (4 out of 7 isolates; 57%)., Conclusions: C. metapsilosis was the most susceptible species to echinocandins, followed by C. orthopsilosis and C. parapsilosis. Anidulafungin was the most active echinocandin against C. parapsilosis complex., (Copyright © 2019 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans , 215  C. dubliniensis , 4,418  C. glabrata species complex, 157  C. guilliermondii ( Meyerozyma guilliermondii ), 676  C. krusei ( Pichia kudriavzevii ), 298  C. lusitaniae ( Clavispora lusitaniae ), 911  C. parapsilosis sensu stricto , 3,691  C. parapsilosis species complex, 36  C. metapsilosis , 110  C. orthopsilosis , 1,854  C. tropicalis , 244 Saccharomyces cerevisiae , 1,409 Aspergillus fumigatus , 389  A. flavus , 130  A. nidulans , 233  A. niger , and 302  A. terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 ( C. albicans ), ERG11 and MRR1 ( C. parapsilosis ), cyp51A ( A. fumigatus ), and CDR2 and CDR1 overexpression ( C. albicans and C. glabrata , respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants., (Copyright © 2018 American Society for Microbiology.)

Objective: To evaluate the importance of Candida glabrata, Candida parapsilosis and their close-related species, Candida bracarensis, Candida nivariensis, Candida metapsilosis and Candida orthopsilosis in patients with oral candidiasis and, to determine the in vitro activities of antifungal drugs currently used for the treatment., Methods: One hundred fourteen isolates of C. glabrata and 97 of C. parapsilosis, previously identified by conventional mycological methods, were analysed by molecular techniques. In vitro antifungal susceptibility to fluconazole, itraconazole, miconazole, and nystatin was evaluated by CLSI M44-A2 disk diffusion test, and by CLSI M27-A3 microdilution for fluconazole., Results: All C. glabrata isolates were identified as C. glabrata sensu stricto, 93 out of 97 C. parapsilosis isolates as C. parapsilosis sensu stricto, three as C. orthopsilosis and one as C. metapsilosis. Candida glabrata was mainly isolated in mixed cultures but C. parapsilosis complex was more frequent in pure culture. Candida metapsilosis and C. orthopsilosis were isolated as pure culture and both species were susceptible to all antifungal agents tested. Most C. glabrata isolates were susceptible to miconazole and nystatin, but resistant to fluconazole and itraconazole. Azole cross resistance was also observed. Candida parapsilosis isolates were susceptible to fluconazole although azole cross resistance to miconazole and itraconazole was observed., Conclusion: This study highlights the importance of accurate identification and antifungal susceptibility testing of oral Candida isolates in order to have an in-depth understanding of the role of C. glabrata and C. parapsilosis in oral candidiasis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.

Killing and postantifungal effects could be relevant for the selection of optimal dosing schedules. This study aims to compare time-kill and postantifungal effects with caspofungin on Candida albicans (C. albicans, Candida dubliniensis, Candida africana) and Candida parapsilosis (C. parapsilosis, Candida metapsilosis, Candida orthopsilosis) clades. In the postantifungal effect experiments, strains were exposed to caspofungin for 1 h at concentrations 0.12-8 μg/mL. Time-kill experiments were conducted at the same concentrations. Caspofungin exhibited a significant and prolonged postantifungal effect (>37 h) with 2 μg/mL against the most strains of C. albicans clade. Against the C. parapsilosis clade, the postantifungal effect was <12 h at 8 μg/mL, except for two strains. Caspofungin was fungicidal against C. albicans, C. dubliniensis and C. metapsilosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients., Aims: To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients., Methods: A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm., Results: The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion., Conclusions: Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription., (Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis.

The aim of this study was to fit anidulafungin in vitro static time-kill data from nine strains of Candida with a pharmacodynamic (PD) model in order to describe the antifungal activity of this drug against Candida spp. Time-kill data from strains of Candida albicans, Candida glabrata and Candida parapsilosis clades were best fit using an adapted sigmoidal Emax model and resulted in a set of PD parameters (Emax, EC50 and Hill factor) for each fungal strain. The data were analysed with NONMEM 7. Anidulafungin was effective in a species- and concentration-dependent manner against the strains of C. glabrata and C. parapsilosis clades as observed with the EC50 estimates. Maximum killing rate constant (Emax) values were higher against C. glabrata and C. parapsilosis complex strains. In conclusion, we demonstrated that the activity of anidulafungin against Candida can be accurately described using an adapted sigmoidal Emax model., (Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 μg/ml for C. albicans, 0.12, 0.25, and 0.03 μg/ml for C. glabrata complex, 4, 2, and 4 μg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 μg/ml for C. tropicalis, 0.25, 1, and 0.25 μg/ml for C. krusei, 0.25, 1, and 0.12 μg/ml for C. lusitaniae, 4, 2, and 2 μg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 μg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

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.

Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 μg/ml) was fungicidal (≥ 3 log10 reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h) differed from C. parapsilosis complex (8.07 ± 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.

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 C. albicans, 5 C. dubliniensis, and 2 C. 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 ≤31 h with ≥0.5 μg/mL for anidulafungin in 4 C. albicans and 1 C. dubliniensis, for caspofungin in 1 C. albicans and 2 C. dubliniensis, and for micafungin in 4 C. albicans and 1 C. dubliniensis. None of echinocandins showed lethality against C. africana. Identification of these new cryptic species and time-kill studies would be recommendable when echinocandin treatment fails., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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 μg/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., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

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.

Objectives: To update the knowledge of the epidemiology of fungaemia episodes in Spain, the species implicated and their in vitro antifungal susceptibilities., Methods: 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., Results: 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 96.5%-99.8% 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%)., Conclusions: 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.

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.

A 13-month prospective multicenter study including 44 hospitals was carried out to evaluate the epidemiology of Candida parapsilosis complex candidemia in Spain. Susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, caspofungin, and micafungin was tested by the microdilution colorimetric method. A total of 364 C. parapsilosis complex isolates were identified by molecular methods: C. parapsilosis (90.7%), Candida orthopsilosis (8.2%), and Candida metapsilosis (1.1%). Most candidemias (C. parapsilosis, 76.4%; C. orthopsilosis, 70.0%; C. metapsilosis, 100%) were observed in adults. No C. orthopsilosis or C. metapsilosis candidemias occurred in neonates. C. parapsilosis was most frequent in adult intensive care unit (28.8%), surgery (20.9%), and internal medicine (19.7%) departments; and C. orthopsilosis was most frequent in hematology (28.6%), pediatrics (12.0%), and neonatology (11.5%) departments. The geographic distribution of C. orthopsilosis and C. metapsilosis was not uniform. According to CLSI clinical breakpoints, all C. orthopsilosis and C. metapsilosis isolates were susceptible to the nine agents tested. Resistance (MICs > 1 mg/liter) was observed only in C. parapsilosis: amphotericin B, posaconazole, itraconazole, and caspofungin (0.3% each), anidulafungin (1.9%), and micafungin (2.5%). Applying the new species-specific fluconazole and echinocandin breakpoints, the rates of resistance to fluconazole for C. parapsilosis and C. orthopsilosis increased to 4.8% and 0.3%, respectively; conversely, for C. parapsilosis they shifted from 1.9 to 0.6% (anidulafungin) and from 2.5 to 0.6% (micafungin). Our study confirms the different prevalence of C. parapsilosis complex candidemia among age groups: neither C. orthopsilosis nor C. metapsilosis was isolated from neonates; interestingly, C. metapsilosis was isolated only from adults and the elderly. The disparity in antifungal susceptibility among species could be important for therapy.

Background: Candida-associated denture stomatitis is a frequent infectious disease. Treatment of this oral condition is difficult because failures and recurrences are common. The aim of this study was to test the in vitro antifungal activity of pure constituents of essentials oils., Methods: Eight terpenic derivatives (carvacrol, farnesol, geraniol, linalool, menthol, menthone, terpinen-4-ol, and α-terpineol), a phenylpropanoid (eugenol), a phenethyl alcohol (tyrosol) and fluconazole were evaluated against 38 Candida isolated from denture-wearers and 10 collection Candida strains by the CLSI M27-A3 broth microdilution method., Results: Almost all the tested compounds showed antifungal activity with MIC ranges of 0.03-0.25% for eugenol and linalool, 0.03-0.12% for geraniol, 0.06-0.5% for menthol, α-terpineol and terpinen-4-ol, 0.03-0.5% for carvacrol, and 0.06-4% for menthone. These compounds, with the exception of farnesol, menthone and tyrosol, showed important in vitro activities against the fluconazole-resistant and susceptible-dose dependent Candida isolates., Conclusions: Carvacrol, eugenol, geraniol, linalool and terpinen-4-ol were very active in vitro against oral Candida isolates. Their fungistatic and fungicidal activities might convert them into promising alternatives for the topic treatment of oral candidiasis and denture stomatitis.

We have evaluated the in vitro activity of anidulafungin (AFG) against 31 strains of Candida parapsilosis sensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive of in vivo outcomes, six strains representing different AFG MICs (0.12 to 2 μg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 μg/ml).

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.

Genitourinary infections by Saccharomyces cerevisiae are rare. Here, we describe eight S. cerevisiae vulvovaginitis episodes where molecular (Affirm VPIII) and conventional microbiological methods (culture and carbohydrate assimilation) have proven to be inadequate for diagnostic purposes. DNA sequencing allowed the correct identification of the pathogen. All isolates were susceptible to most antifungal agents, with two of them also found to be susceptible-dose-dependent to itraconazole.

We have developed a monoclonal antibody (MAb), C7, that reacts with the Als3p and enolase present in the Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of MAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in the presence of a subinhibitory concentration of MAb C7 (12.5 μg/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with MAb C7. Of these, 28 were found to be upregulated and 21 were found to be downregulated. The categories of upregulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the downregulated genes (8/21). Results were validated by real-time PCR. Since these effects resembled those found under iron-limited conditions, the activity of MAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking the TPK1 gene and, to a lesser extent, the TPK2 gene were less sensitive to the candidacidal effect of MAb C7. FeCl(3) or hemin at concentrations of ≥ 7.8 μM reversed the candidacidal effect of MAb C7 on C. albicans in a concentration-dependent manner. The results presented in this study provide evidence that the candidacidal effect of MAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans.

Micafungin is a semisynthetic lipopeptide developed from Coleophoma empetri, which blocks the synthesis of β-1,3-D-glucan, an essential component of the fungal wall, though non-competitive inhibition of β-1,3-D-glucan synthetase. Micafungin is a dose-dependent candidacidal agent with excellent in vitro efficacy against most Candida spp. including species resistant to amphotericin B, such as Candida lusitaniae, several azoles, such as C. glabrata or C. krusei, and isolates not susceptible to other echinocandins. Moreover, this drug is active against Candida biofilms. Micafungin is a first-line drug for the treatment of candidemias and invasive candidiasis in adults and children (including neonates). This drug is approved for use in the treatment of invasive candidiasis and Candida esophagitis, as well as in the prophylaxis of Candida infections in hematopoietic stem cell transplant recipients or those at risk of prolonged neutropenia. Micafungin can be used both in the treatment and prevention of candidiasis in neonates, children, adolescents, adults, and the elderly, making it highly useful in patient groups in which the use of other antifungal drugs has not been authorized., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

The in vitro antifungal activity of posaconazole was tested against 315 yeast clinical isolates and 11 ATCC reference strains by means an agar diffusion method (Neosensitabs, Rosco,Denmark) based in CLSI M44-A2 document. Posaconazole activity was excellent against Cryptococcus and Rhodotorula species studied and showed very good activity against most species of Candida tested. A total of 13 clinical isolates (4.1%) were resistant: Candida albicans (n=5), Candida glabrata (n=5), Candida tropicalis (n=1), Geotrichum australiensis (n=1) and Geotrichum capitatum (n=1). Our results suggest posaconazole is an effective antifungal agent against the most clinically important yeasts species (92.7% of susceptibility). Agar diffusion method provides good conditions for the posaconazole susceptibility study in the routine laboratory.

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.

Candida dubliniensis commonly shows paradoxical or trailing growth effects in vitro in the presence of echinocandins. We tested the in vitro activities of anidulafungin, caspofungin, and micafungin against clinical isolates of C. dubliniensis and evaluated the efficacy of these drugs in two murine models of systemic infection. The three echinocandins were similarly effective in the treatment of experimental disseminated infections with C. dubliniensis strains showing or not showing abnormal growth in vitro.

Background: Most recalcitrant infections are associated to colonization and microbial biofilm development. These biofilms are difficult to eliminate by the immune response mechanisms and the current antimicrobial therapy., Aim: To describe the antifungal of micafungin against fungal biofilms based in the scientific and medical literature of recent years., Methods: We have done a bibliographic retrieval using the scientific terms "micafungin", "activity", "biofilm", "Candida", "Aspergillus", "fungi", "mycos"*, susceptibility, in PubMed/Medline from the National Library of Medicine from 2006 to 2009., Results: Most current antifungal agents (amphotericin B and fluconazole) and the new azole antifungals have no activity against fungal biofilms. However, micafungin and the rest of echinocandins are very active against Candida albicans, Candida dubliniensis, Candida glabrata, and Candida krusei biofilms but their activities are variable and less strong against Candida tropicalis and Candida parapsilosis biofilms. Moreover, they have not activities against the biofilms of Cryptococcus y Trichosporon., Conclusions: The activity of micafungin against Candida biofilms gives more strength to its therapeutic indication for candidaemia and invasive candidiasis associated to catheter, prosthesis and other biomedical devices.

Background: Micafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses with a wide antifungal spectrum for the most common pathogenic fungi. Micafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3- D-glucan synthesis, an essential molecule for the cell wall architecture, with different con sequences for Candida and Aspergillus, being micafungin fungicide for the former and fungistatic for the latter., Aim: To describe the in vitro antifungal spectrum of micafungin based in the scientific and medical lite rature of recent years., Methods: We have done a bibliographic retrieval using the scientific terms, "micafungin", "activity", "Candida", "Aspergillus", "fungi", "mycos*", "susceptibility", in PubMed/Medline from the National Library of Medicine de EE.UU. from 2005 to 2009., Results: We can underline that most than 99% of Candida isolates are susceptible to < or = 2microg/ml of micafungin. MIC are very low (< or = 0.125microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2microg/ml. The activity of micafungin is excellent against those medical important species of Aspergillus. However, its activity is very low against Cryptococcus and the Zygomycetes., Conclusions: The excellent activity of micafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.

Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common pathogenic fungi. Anidulafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3-D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being anidulafungin fungicide for the former and fungistatic for the latter. This review describes the in vitro antifungal spectrum of anidulafungin based in the scientific and medical literature of recent years. We can underline that most than 99% of Candida isolates are susceptible to < or = 2 microg/ml of anidulafungin. MIC are very low (< or =0.125 microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2 microg/ml. An excellent activity of anidulafungin has been also described against Aspergillus, Pneumocystis and other fungi. However, its activity is very low against Cryptococcus and the Zygomycetes. The excellent activity of anidulafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.

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.

The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of Candida. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assays.

The aim of this study was to evaluate the in vitro activities of voriconazole and fluconazole against Candida glabrata and Candida krusei isolated from blood during a 14-year period (1990-2003) at the tertiary care hospital of Cruces (Barakaldo, Spain). The in vitro activities of fluconazole and voriconazole against 28 isolates of C. glabrata and 15 isolates of C. krusei were determined by the Clinical and Laboratory Standards Institute disk diffusion method. Of the 28 C. glabrata isolates tested, 24 (85.7%) were susceptible (S) to fluconazole, 2 (7.1%) were susceptible dose-dependent (S-DD) and 2 (7.1%) were resistant (R). All C. krusei isolates were classified as R to fluconazole. Resistance to voriconazole was observed in one isolate each of C. glabrata (3.6%) and C. krusei (6.7%), and one isolate of each species was S-DD. These results were confirmed by the Sensititre YeastOne and Etest methods, with good comparative results. Voriconazole was very active in vitro against C. glabrata and C. krusei blood isolates and the resistance observed was not related to the introduction of voriconazole in the therapeutic schedule of the hospital. These facts support the usefulness of voriconazole as a therapeutic tool for candidaemia caused by these species.

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 activity of caspofungin and voriconazole 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., ((c) 2007 S. Karger AG, Basel.)

Invasive infections caused by Candida spp. are increasing worldwide and are becoming an important cause of morbidity and mortality in immunocompromised patients. A large number of manifestations of candidiasis are associated with the formation of biofilms on inert or biological surfaces. Candida spp. biofilms are recalcitrant to treatment with conventional antifungal therapies. The aim of this study was dual 1) to determine the prevalence of biofilm producers among clinical isolates from catheter (16 C. albicans ) and blood culture (2 C. albicans and 30 C. tropicalis), and 2) to determine the activity of amphotericin B and anidulafungin against C. albicans and C. tropicalis biofilms of 24 and 48 hours of maturation. Biofilms were developed using a 96-well microtitre plate model and production and activity of antifungal agents against biofilms were determined by the tetrazolium (XTT) reduction assay. Of catheter and blood isolates, 62.5 and 56.25%, respectively, produced biofilms. By species, 68.42% of C. albicans and 53.33% of C. tropicalis were biofilm producers. C. albicans biofilms showed more resistance to amphotericin B and anidulafungin than their planktonic counterparts. Complete killing of biofilms was never achieved, even at the highest concentrations of the drugs tested. Anidulafungin displayed more activity than amphotericin B against C. albicans biofilms of 24 hours of maturation (GM MIC 0.354 vs. 0.686 microg/ml), but against C. tropicalis biofilms amphotericin B was more active (GM MIC 11.285 vs. 0.476 microg/ml). In contrast, against biofilms with 48 hours maturation, amphotericin B was more active against both species.

The in vitro activity of the combination micafungin + itraconazole was evaluated against 105 strains of six species of Candida. The highest percentage of synergy was obtained against Candida albicans (50%) and the lowest against Candida tropicalis (0%).

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.

Two milestones have characterized the last decades in Medical Mycology: the continuous increase in incidence of invasive mycoses and the discovery of new antifungal drugs that have allowed the successful treatment of these severe infections. This monography presents the most relevant studies on the present situation of invasive mycoses, its diagnosis and treatment, as well as data confirming the important role of voriconazole in their treatment.

Using a reference microdilution method, we studied the antifungal susceptibility to voriconazole and fluconazole of 304 clinical isolates from four species of onychomycosis-causing dermatophytes, 196 isolates of dermatophytes not related to nail infection as well as Scopulariopsis brevicaulis, Fusarium spp. and Scytalidium dimidiatum. Results showed a high antifungal activity of voriconazole against dermatophytes (geometric mean minimal inhibitory concentration (MIC)=1.14 microg/mL; MIC for 50% of the organisms (MIC(50))=0.062 miccrog/mL; MIC for 90% of the organisms (MIC(90))=0.25 microg/mL). For S. brevicaulis, the in vitro activity of voriconazole was considerably lower (geometric mean MIC=8.52 microg/mL; MIC(50) and MIC(90)=16 microg/mL). Although voriconazole is not among the drugs recommended for the management of onychomycosis, it can be a useful alternative for recalcitrant infections.