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Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles and echinocandins. In this study, anidulafungin plus posaconazole have shown efficacy against a murine systemic infection by three strains of Aspergillus fumigatus. The combination increased mice survival and reduced burden in the kidneys over the corresponding monotherapies and voriconazole. Clearance of kidneys was observed in 62% to 100% of animals (strain dependant). We observed good in vitro- in vivo correlation when a cutoff < 1 was indicative of synergy. Our results showed that the combination could be a therapeutical option, especially against infections refractory to the first line therapy., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The in vitro activity of posaconazole (PSC) and voriconazole (VRC) was tested by using time-kill studies against 3 strains of Candida lusitaniae. Both drugs showed fungistatic activity against all strains. The efficacy of those compounds was evaluated by reducing kidney fungal burden and by determining (1→3)-β-d-glucan serum levels in a murine model of invasive infection of C. lusitaniae. The therapies tested were VRC at 10, 25, or 40 mg/kg/day and PSC at 5, 12.5, or 20 mg/kg/twice a day. All the dosages showed efficacy in a dose-dependant manner being high doses of both antifungals able to sterilize some kidneys after 10 days. With the exception of the strain FMR 9474, against which PSC was more effective than VRC, no differences in reducing tissue burden were found between the treatments. All doses of both antifungals were able to significantly reduce (1→3)-β-d-glucan serum levels with no significant differences between treatments and between the same doses of both drugs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)-β-D-glucan levels in serum, tissue burden reduction, and histopathology., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Aspergillus fumigatus is the main mold causing invasive fungal infection that shows high mortality rates. Therapeutic failure and the increase in drug resistance make it necessary to explore alternative treatments for this infection. We have evaluated the efficacy of amphotericin B at 0.8 mg/kg or 0.3 mg/kg of body weight combined with 40 mg/kg of posaconazole against three A. fumigatus isolates in a murine model of disseminated infection. The combination of the polyene and the azole led to a greater increase in survival and a significantly greater reduction in tissue burden than monotherapies., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objectives: Scedosporium infections are associated with high therapeutic failure rates. Combination therapy may be an alternative approach to improve outcome. The in vitro and in vivo efficacy of micafungin plus posaconazole or plus voriconazole was investigated herein., Methods: Scedosporium boydii (n = 17) and Scedosporium apiospermum (n = 26) were tested using the chequerboard method according to CLSI M38-A2 guidelines and the fractional inhibitory concentration index (FICI) was evaluated. In vivo outcome of micafungin plus posaconazole or micafungin plus voriconazole against two isolates of each of the mentioned species was evaluated in a well-established, immunocompromised, haematogenous murine model of systemic scedosporiosis. Survival and tissue burden in kidneys and brain were investigated., Results: The FICI category of 'no interaction' was most frequent, while 'synergism' or 'antagonism' was rarely observed. FICI failed to predict the in vivo outcome of both combinatorial treatment strategies. In vivo outcome was strain-dependent rather than species-dependent, even though effects on fungal tissue burden were more pronounced for S. boydii. Both combinations improved survival significantly when compared with untreated controls and micafungin monotherapy. Voriconazole and posaconazole did not differ in their efficacy and micafungin failed to be effective. Combinations were by trend better than voriconazole and posaconazole as single therapy, but statistically significant differences were lacking., Conclusions: No benefit of the azole/echinocandin combination was found when compared with voriconazole and posaconazole monotherapies. FICI failed to predict the outcome of in vivo drug combinations in the murine study., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Despite the use of recommended therapies, invasive infections by Aspergillus terreus show a poor response. For years, investigative studies on the failure of therapy of fungal infections have focused on in vitro susceptibility data. However, it is well known that low minimum inhibitory concentrations (MICs) are not always predictive of response to therapy despite a correct dosage schedule. Many experimental and clinical studies have tried to establish a relationship between MICs and outcome in serious fungal infections but have come to contradictory and even surprising conclusions. The success or failure of treatment is determined by many factors, including the in vitro susceptibility of the causative fungal isolate, the pharmacokinetics/pharmacodynamics of the drug used for treatment, pharmacokinetic variability in the population, and the underlying disease that patients suffer. To try to understand this poor response to treatment, available data on the in vitro susceptibility of A. terreus, the experimental and clinical response to amphotericin B, triazoles and echinocandins, and the pharmacokinetics/pharmacodynamics of these antifungals have been reviewed. Of special interest are the fungistatic activites of these drugs against A. terreus and the high interpatient variability of serum drug levels observed in therapy based on triazoles, which make monitoring of infected patients necessary., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The efficacy of voriconazole (VRC) was evaluated against two strains of each of the two most common species causing sporotrichosis, Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, using a murine model of disseminated infection. Voriconazole was administered at doses of 20 or 40 mg kg(-1) per day by gavage. The drug showed some efficacy, especially at 40 mg kg(-1) per day, in prolonging the survival and reducing fungal load in spleen and liver in mice infected with S. schenckii, whereas in animals infected with S. brasiliensis the drug did not work., (© 2013 Blackwell Verlag GmbH.)

We have evaluated the in vitro activity of voriconazole against 61 strains of Aspergillus fumigatus by using broth microdilution, disk diffusion, and minimal fungicidal concentration procedures. We observed an excellent correlation between the results obtained with the three methods. Five percent of the strains showed MICs greater than or equal to the epidemiological cutoff value (ECV; 1 μg/ml). To assess whether MICs were predictive of in vivo outcome, we tested the efficacy of voriconazole at 25 mg/kg of body weight daily in an immunosuppressed murine model of disseminated infection using 10 strains representing various patterns of susceptibility to the drug as determined by the in vitro study. Voriconazole prolonged survival and reduced fungal load in the kidneys and brain in those mice infected with strains with MICs of ≤0.25 μg/ml, while in mice infected with strains with MICs of 0.5 to 2 μg/ml, the efficacy was varied and strain dependent and in mice infected with the strain with a MIC of 4 μg/ml, the antifungal did not show efficacy. Voriconazole reduced galactomannan antigenemia against practically all strains with a MIC of <4 μg/ml. Our results demonstrate that some relationship exists between voriconazole MICs and in vivo efficacy; however, further studies testing additional strains are needed to better ascertain which MIC values can predict clinical outcome.

We evaluated the efficacy of voriconazole against nine strains of Aspergillus terreus with different MICs (0.12 to 4 μg/ml) by using a murine model. Markers of efficacy included survival, tissue burden, galactomannan antigenemia, and drug serum levels. Voriconazole was especially effective in prolonging survival and reducing the fungal load in infections by strains that showed MICs that were less than or equal to the epidemiological cutoff value (1 μg/ml). In vitro data might be useful for predicting the outcome of A. terreus infections.

We have determined the in vitro activity of amphotericin B (AMB) and posaconazole (PSC) against Saksenaea vasiformis using broth microdilution and disk diffusion methods and determined the minimal fungicidal concentration (MFC). PSC was found to have the greatest in vitro activity in all cases and was the most efficacious in prolonging survival and reducing the fungal load in an immunocompetent murine model of disseminated infection caused by four strains of the fungus.

We tried to correlate the in vitro activity and the in vivo efficacy of voriconazole (VRC) and posaconazole (POS) against Aspergillus flavus and Aspergillus niger. The in vitro susceptibility of a large set of isolates was determined by broth microdilution and disk diffusion methods, while the in vivo efficacy was assessed in a murine model of disseminated infection. For A. flavus, VRC showed efficacy even for strains with MICs above the epidemiologic cutoff value (ECV) (1 μg/mL). For A. niger, VRC was ineffective against those strains for which the MIC was 1 dilution below the corresponding ECV (2 μg/mL). POS showed efficacy against all the strains of both species included in the study, although isolates with MICs > ECV were not tested., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: We evaluated the in vitro activity of posaconazole and amphotericin B against several clinical strains of the mucoralean fungus Apophysomyces variabilis, and their efficacy in a murine model of disseminated infection caused by that fungus., Methods: The in vitro susceptibility of seven strains of A. variabilis to posaconazole and amphotericin B was determined by using a broth microdilution method. The in vivo efficacy of both drugs, posaconazole at 20 mg/kg twice daily orally by gavage and amphotericin B at 0.8 mg/kg once daily intravenously, was evaluated against six of the strains previously tested in vitro using immunocompetent mice., Results: In general, MICs of both drugs were within the range of susceptibility or intermediate susceptibility. Posaconazole and amphotericin B were able to significantly reduce the percentages of positive cultures in the affected tissues. However, in general, posaconazole significantly improved survival (median, 23 days; range, 7-30 days) compared with untreated controls (median, 6 days; range, 4-7 days) and, in some cases, with respect to the animals treated with amphotericin B (median, 15 days; range, 5-30 days)., Conclusions: Our results demonstrate the efficacy of posaconazole in the treatment of a disseminated murine infection caused by A. variabilis. However, further clinical studies are required to ascertain the potential use in human infections caused by this fungus.

The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥ 3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivo studies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivo efficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloides or by strains of Mucor not identified to the species level.

We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

The efficacy of the combination of anidulafungin (AFG) at 1 mg/kg plus voriconazole (VRC) at 25 mg/kg was evaluated in a murine model of disseminated infection by Aspergillus flavus using three isolates previously tested in vitro. All the combinations showed indifferent in vitro interaction with the exception of one, which showed synergy. In general, the combined treatment prolonged the survival and reduced the fungal load in comparison with AFG alone, and only in a few cases, it improved the results of the VRC monotherapy. The combination of the two drugs and VRC alone reduced the galactomannan levels in serum in comparison with the control group.

Meningitis is one of the most fatal manifestations of cryptococcosis, even with specific treatment. Combination of a prompt diagnosis and appropriate therapy are critical to reduce the fungal load and the inflammatory response effects of the proliferation of yeast into the central nervous system (CNS). Mice with experimental acute meningitis caused by Cryptococcus neoformans were treated with liposomal amphotericin B (L-AmB) administered intrathecally (i.t.c.) at 0.006 mg/kg weekly or intravenously (i.v.) at 10 mg/kg daily or with voriconazole (VCZ) administered orally at 30 mg/kg per dose twice daily or with combinations of both drugs, i.e. L-AmB i.t.c.+VCZ or L-AmB i.v.+VCZ at the same doses as used in the monotherapies. All treatments significantly increased the survival of animals in comparison with the control group, with VCZ being less effective in comparison with all other treatments (P ≤ 0.012). All treatments, with the exception of VCZ (P=0.533), reduced fungal burdens in the brain in comparison with controls. The combination of L-AmB i.t.c.+VCZ showed a synergistic effect in the reduction of fungal load that was significantly superior to any tested therapy (P ≤ 0.039). Histologically, untreated animals showed a marked inflammatory response with massive fungal cells in the meninges, whilst treated animals showed a variable number of fungal cells in the CNS, with the exception of animals receiving L-AmB i.t.c.+VCZ in which neither yeasts nor inflammation were observed., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Using a murine model of disseminated infection by two strains of Fusarium verticillioides, we have evaluated the efficacy of high doses of amphotericin B (AMB) (3 mg/kg of body weight/day), voriconazole (VRC) (60 mg/kg of body weight/day), posaconazole (PSC) (100 mg/kg of body weight/day), and the combinations of AMB plus VRC or PSC. In general, our results were very modest. Neither combination was superior to the respective monotherapies. VRC alone and in combination with AMB was able to prolong survival but not to reduce tissue burden, and AMB plus PSC was able to reduce fungal load in organs but not to prolong survival.

Posaconazole (PSC) is an antifungal drug recommended as an alternative for the treatment of invasive aspergillosis in patients who are refractory or intolerant to primary antifungal therapy. We have evaluated the in vitro activity of PSC against 21 strains of the Aspergillus terreus complex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the two in vitro methods used. We developed a murine model of disseminated infection to evaluate the efficacy of PSC at 5, 10, or 20 mg/kg of body weight twice a day by using 6 different strains chosen randomly. PSC showed good efficacy, especially at 20 mg/kg, as measured by prolonged survival, tissue burden reduction, histopathology, and lowered galactomannan levels. The PSC levels in serum on the fourth day of treatment were higher than the MICs for the strains tested.

We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.

Objectives: We have evaluated the efficacy of posaconazole, itraconazole and amphotericin B in murine models of disseminated infection caused by Exophiala spp., Methods: Immunosuppressed mice were treated with posaconazole at 10, 20 or 40 mg/kg/day orally (po), amphotericin B at 1.5 mg/kg/day intraperitoneally (ip) or itraconazole at 50 mg/kg/day po. Treatment began 1 day after infection and continued for 7 days post-infection. Two strains of each of the three most relevant clinical species, i.e. Exophiala dermatitidis, Exophiala oligosperma and Exophiala xenobiotica, were tested., Results: Posaconazole showed the highest efficacy in mice infected with E. dermatitidis, the only species that showed a high neurotropism, while the three drugs showed a similarly good activity against E. oligosperma and E. xenobiotica infections., Conclusions: The results suggest that posaconazole may have a clinical role in the treatment of disseminated infections caused by Exophiala species, especially in those with CNS invasion.

We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs tablet diffusion method, and minimal fungicidal concentration (MFC) determination. In general, PSC showed low MICs against this fungus, and the MICs correlated with the inhibition zone diameters. Most of the MFCs, however, were from 1 to 4 dilutions higher than their corresponding MICs. We then investigated the efficacies of several different doses of PSC in a murine model. All treatments began 24 h after challenge and lasted for 7 days. The drug was administered twice a day to mice infected with three strains that showed intermediate PSC susceptibility (MIC = 2 microg/ml) and three PSC-susceptible strains (MIC = 0.25 microg/ml). A dose of 10 mg/kg of body weight was ineffective, while doses of 20 and 30 mg/kg prolonged the survival of the mice. The 50 strains tested were segregated into two groups on the basis of the in vitro data. For the group with the most strains (85%), the strains had low PSC MICs, mice infected with the strains showed higher rates of survival (30 to 40%), and PSC was able to reduce the fungal load in the kidney and less regularly in the brain. For the second group (15% of the strains), the strains had intermediate PSC MICs, mice infected with the strains had lower survival rates (10 to 20%), and PSC treatment resulted in variable and no reductions in the fungal loads in the kidneys and brains, respectively.

We studied the efficacy of voriconazole (VRC) and amphotericin B (AMB) in an immunosuppressed murine model of disseminated infection by two strains of Paecilomyces lilacinus. Mice were treated with VRC 60 mg/kg/day orally or AMB 3mg/kg/day intraperitoneally, beginning 1 day after infection and continuing for 9 days. To avoid rapid clearance of VRC, animals receiving VRC and the control group were given grapefruit juice instead of water. VRC significantly prolonged survival with respect to the group treated with AMB and the control group for both strains (P=0.005 and P<0.0001, respectively, for strain FMR 5522; and P=0.0002 and P<0.0001, respectively, for strain FMR 8252). VRC reduced the fungal load in the spleen, kidneys and liver of infected mice for both strains tested. Survival of mice challenged with strain FMR 8252 treated with AMB did not differ from that of the control group (P=0.223), being worse than that of the mice treated with VRC (P=0.0002). AMB was not able to reduce the tissue burden in any organ with respect to the control group for both strains studied., ((c) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

We evaluated the efficacy of amphotericin B (1.5mg/kg/day), voriconazole (60mg/kg/day) and posaconazole (60mg/kg/day) in a murine model of systemic infection caused by Neoscytalidium dimidiatum. All the treatments were able to prolong survival and to reduce the tissue burden in the spleen and kidneys of infected mice. Neither voriconazole nor posaconazole improved the results achieved with amphotericin B., (Copyright 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

We have evaluated the efficacy of posaconazole, amphotericin B, and itraconazole in a murine model of disseminated infection by Fonsecaea monophora. Of these three antifungal drugs tested, posaconazole prolonged survival significantly and reduced the fungal load in most of the organs tested. Bioassay studies demonstrated the relationship between posaconazole levels and dose escalation in serum and brain tissue. Posaconazole may have a clinical role in the treatment of disseminated infections by F. monophora.

We evaluated the efficacy of posaconazole against Candida tropicalis in a systemic infection model with immunosuppressed mice. Posaconazole at 50 mg/kg of body weight/day prolonged the survival of mice and reduced the fungal tissue burden of mice infected with any of the five strains tested, with the exception of one strain that had a high MIC against this drug. Our results demonstrate the efficacy of posaconazole in the treatment of invasive murine infection caused by C. tropicalis.

A broth microdilution method was used to evaluate the in vitro activities of seven antifungal agents against 15 clinical strains of Rhizopus microsporus. Amphotericin B (AMB) and posaconazole (POS) were the most active drugs. In a model of disseminated R. microsporus infection in immunosuppressed mice, we studied the efficacy of POS administered once or twice daily against four of the strains previously tested in vitro and compared it with that of liposomal AMB (LAMB). LAMB was the most effective treatment for the two strains with intermediate susceptibility to POS. For the two POS-susceptible strains, LAMB and POS at 20 mg/kg of body weight twice a day orally showed similar efficacies. The in vivo efficacy of POS administered twice a day orally correlated with the in vitro susceptibility data and the serum drug concentrations.

We evaluated the efficacies of posaconazole and voriconazole in comparison with that of amphotericin B in a systemic murine infection by Candida krusei. Posaconazole at 50 mg/kg/day and voriconazole at 40 and 60 mg/kg/day prolonged survival and reduced the fungal tissue burden in the kidneys of mice similarly to amphotericin B at 1.5 mg/kg/day and liposomal amphotericin B at 10 mg/kg/day. None of the treatments tested completely resolved the infection.

We have evaluated the efficacies of micafungin, amphotericin B, and voriconazole, alone and in double and triple combinations, in a murine model of systemic infection by Scedosporium prolificans. Micafungin combined with voriconazole or amphotericin B was the most effective, these being the only treatments able to prolong survival and to reduce the fungal load in the kidneys and brain. Triple combinations of these drugs did not improve the results obtained with double combinations.

We have evaluated and compared the efficacies of high doses of amphotericin B (AMB; 3 mg/kg of body weight/day), voriconazole (60 mg/kg), and posaconazole (PSC; 100 mg/kg) alone and combined in a murine model of disseminated infection by Fusarium oxysporum. The combination of AMB with PSC showed the best results, prolonging the survival of mice and reducing their organ fungal loads. This combination might constitute a therapeutic option for those infections where monotherapies fail.

Objectives: We have compared the efficacy of posaconazole and amphotericin B in an experimental murine model of paecilomycosis., Methods: Immunosuppressed mice were treated with posaconazole at 25, 50, 75 or 100 mg/kg/day orally, amphotericin B at 1.5 or 3 mg/kg/day intraperitoneally or liposomal amphotericin B at 5 mg/kg/day intravenously. Treatment began 1 day after infection and continued for 10 days post-infection. Two strains of Paecilomyces lilacinus were tested., Results: Posaconazole at 50 mg/kg/day was the only treatment able to significantly reduce fungal loads in the spleens, kidneys and livers of the mice infected by each of the two strains., Conclusions: The results suggest that posaconazole may have a clinical role in the treatment of disseminated paecilomycosis.

In a murine model of disseminated zygomycosis, low doses of amphotericin B (0.3 mg/kg body weight/day) combined with posaconazole (40 mg/kg/day) prolonged survival and reduced tissue burden with respect to that of controls and that of both drugs administered alone. Results were similar to those obtained with amphotericin B given alone at 0.8 mg/kg/day.

Voriconazole is a broad-spectrum antifungal drug belonging to triazoles class. Recently, it has been recommended for the treatment of invasive candidiasis in non neutropenic patients. In addition, this drug has showed clinical efficacy in the treatment of fungal infections caused by Candida species other than Candida albicans, and also in several other infections caused by less common fungi, such as Aspergillus terreus, Fusarium and Scedosporium.

Objectives: We studied the efficacy of voriconazole compared with amphotericin B in a murine model of central nervous system infection by Cryptococcus neoformans. Infection was established intracerebrally., Methods: Mice were treated with voriconazole at 10, 40 or 60 mg/kg/day orally or with amphotericin B at 1.5 mg/kg/day intraperitoneally. Treatment began 1 day after infection and continued for 10 days post-infection. Tissue burden studies were performed on day 7 and 1 day after the treatment finished., Results: Both drugs were able to significantly prolong survival with respect to the control group. The highest tissue burden reduction was achieved with voriconazole at 60 mg/kg/day., Conclusions: We have developed a murine model of cryptococcal central nervous system infection and demonstrated that voriconazole has a potential for the treatment of cryptococcosis.

We have evaluated the efficacy of voriconazole (VRC) in a systemic infection by Trichosporon asahii in immunosuppressed guinea pigs. VRC was more effective than amphotericin B in prolonging survival and reducing tissue burden. The best results were obtained with VRC at 10 mg/kg of body weight/day.

We have evaluated the efficacy of voriconazole (VRC) in a systemic infection by Scedosporium apiospermum in immunodepressed guinea pigs. Animals were infected with two strains; one required a VRC MIC of 0.5 to 1 microg/ml, common for this fungus, and the other required a high MIC (8 microg/ml), unusual in this species. VRC prolonged survival and reduced fungal load in kidney and brain tissues of the animals infected with the first strain but was unable to prolong survival or to reduce fungal load in brain tissue for the latter strain.

We have evaluated the efficacy of voriconazole (VRC) in a murine model of systemic infection by Scedosporium apiospermum. The survival of mice treated with VRC at 5, 20, or 40 mg/kg/day was greater than that of the control group (P< or =0.0009). VRC reduced the tissue burden in the spleen and brain (P<0.001 in both organs) in comparison with that of the control group.

Chaetomium is an unusual etiological agent of human infections, but the mortality rate among immunocompromised patients is considerably greater than that among nonimmunocompromised individuals. We investigated the in vitro antifungal susceptibilities to novel antifungal agents of 19 strains belonging to three species of Chaetomium which have been involved in human infections, i.e., Chaetomium globosum, C. atrobrunneum, and C. nigricolor, and one strain of the closely related species Achaetomium strumarium. A modification of the NCCLS reference microdilution method (M38-A) was used to evaluate the in vitro activities of ravuconazole, voriconazole, albaconazole, and micafungin. Micafungin was not active at all, while the geometric mean MICs and minimum effective concentrations of the three triazoles were less than 0.5 and 0.4 micro g/ml, respectively.

There are no effective therapeutics for treating invasive Scedosporium prolificans infections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearing S. prolificans from tissue (P < 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P < 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.

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• Azole-resistant Aspergillus isolates have increased alarmingly in recent years, translating into clinical failures. • Resistance mechanisms involve cyp51 genes, efflux pumps and other signalling pathways. • Analysing molecular mediators of azole resistance provides valuable data to manage azole-resistant Aspergillus isolates. Aspergillus fumigatus is the main causal agent of invasive aspergillosis (IA), however other species of the genus can also cause IA, such as Aspergillus flavus, Aspergillus terreus, Aspergillus niger and related cryptic species. This infectious disease mainly affects immunosuppressed patients and is linked to elevated mortality rates. As voriconazole is the treatment of choice for this condition, the relevant increase in the number of azole-resistant isolates in recent years has gathered alarming attention, as it also translates into an increase in clinical failures. In this review, we summarise and discuss the azole resistance molecular data described to date in the most clinically prevalent sections of Aspergillus , including mechanisms involving the target proteins Cyp51 and ATP-binding cassette (ABC) or major facilitator superfamily (MFS) efflux pumps. Other resistance mechanisms proposed but not yet fully characterised are also discussed. [ABSTRACT FROM AUTHOR]