scholarly journals MIC Values of Voriconazole Are Predictive of Treatment Results in Murine Infections by Aspergillus terreus Species Complex

2013 ◽  
Vol 57 (3) ◽  
pp. 1532-1534 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
Deanna A. Sutton ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
...  
Keyword(s):  
Species Complex ◽  
Aspergillus Terreus ◽  
Serum Levels ◽  
Treatment Results ◽  
Cutoff Value ◽  
Content Type ◽  
Fungal Load ◽  
Tissue Burden ◽  
Murine Infections

ABSTRACTWe evaluated the efficacy of voriconazole against nine strains ofAspergillus terreuswith 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 vitrodata might be useful for predicting the outcome ofA. terreusinfections.

scholarly journals Evaluation of the Efficacies of Amphotericin B, Posaconazole, Voriconazole, and Anidulafungin in a Murine Disseminated Infection by the Emerging Opportunistic Fungus Sarocladium (Acremonium)kiliense

2013 ◽  
Vol 57 (12) ◽  
pp. 6265-6269 ◽  
Author(s):  
Fabiola Fernández-Silva ◽  
Javier Capilla ◽  
Emilio Mayayo ◽  
Deanna A. Sutton ◽  
Pilar Hernández ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Survival Rates ◽  
Systemic Infection ◽  
Serum Levels ◽  
Antifungal Drugs ◽  
Content Type ◽  
Animal Survival ◽  
Fungal Load ◽  
High Mics

ABSTRACTWe evaluated and compared the efficacies of different antifungal drugs againstSarocladium kiliense(formerlyAcremonium kiliense), a clinically relevant opportunistic fungus, in a murine model of systemic infection. Three clinical strains of this fungus were tested, and the therapy administered was as follows: posaconazole at 20 mg/kg of body weight (twice daily), voriconazole at 40 mg/kg, anidulafungin at 10 mg/kg, or amphotericin B at 0.8 mg/kg. The efficacy was evaluated by prolonged animal survival, tissue burden reduction, and (1→3)-β-d-glucan serum levels. In general, the four antifungal drugs showed high MICs and poorin vitroactivity. The efficacy of the different treatments was only modest, since survival rates were never higher than 40% and no drug was able to reduce fungal load in all the organs for the three strains tested. Posaconazole, in spite of its high MICs (≥16 μg/ml), showed the highest efficacy. The (1→3)-β-d-glucan serum levels were equally reduced by all drugs evaluated.

scholarly journals In VitroActivity andIn VivoEfficacy of Posaconazole in Treatment of Murine Infections by Different Isolates of theAspergillus terreusComplex

2010 ◽  
Vol 55 (2) ◽  
pp. 676-679 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
M. M. Rodríguez ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
...  
Keyword(s):  
Body Weight ◽  
Murine Model ◽  
Aspergillus Terreus ◽  
Broth Microdilution ◽  
Level Of Activity ◽  
Tissue Burden ◽  
Different Strains ◽  
High Level ◽  
Murine Infections

ABSTRACTPosaconazole (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 thein vitroactivity of PSC against 21 strains of theAspergillus terreuscomplex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the twoin vitromethods 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.

scholarly journals Evaluation of theIn VitroActivity of Voriconazole As Predictive ofIn VivoOutcome in a Murine Aspergillus fumigatus Infection Model

2013 ◽  
Vol 57 (3) ◽  
pp. 1404-1408 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
Enrique Calvo ◽  
Deanna A. Sutton ◽  
Annette W. Fothergill ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Infection Model ◽  
Broth Microdilution ◽  
Excellent Correlation ◽  
Cutoff Value ◽  
Content Type ◽  
Fungal Load ◽  
Strain Dependent

ABSTRACTWe have evaluated thein vitroactivity of voriconazole against 61 strains ofAspergillus fumigatusby 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 ofin vivooutcome, 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 thein vitrostudy. 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 andin vivoefficacy; however, further studies testing additional strains are needed to better ascertain which MIC values can predict clinical outcome.

scholarly journals Method-Dependent Epidemiological Cutoff Values for Detection of Triazole Resistance in Candida and Aspergillus Species for the Sensititre YeastOne Colorimetric Broth and Etest Agar Diffusion Methods

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
A. Espinel-Ingroff ◽  
J. Turnidge ◽  
A. Alastruey-Izquierdo ◽  
F. Botterel ◽  
E. Canton ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Species Complex ◽  
Susceptibility Testing ◽  
Yeast Species ◽  
Sensu Stricto ◽  
Wild Type ◽  
Pichia Kudriavzevii ◽  
Cutoff Value ◽  
Content Type ◽  
Clavispora Lusitaniae

ABSTRACT 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.

scholarly journals Novel Effective Bacillus cereus Group Species “Bacillus clarus” Is Represented by Antibiotic-Producing Strain ATCC 21929 Isolated from Soil

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Marysabel Méndez Acevedo ◽  
Laura M. Carroll ◽  
Manjari Mukherjee ◽  
Emma Mills ◽  
Lingzi Xiaoli ◽  
...  
Keyword(s):  
Bacillus Cereus ◽  
Hela Cells ◽  
Species Complex ◽  
Taxonomic Classification ◽  
Phenotypic Characterization ◽  
Pathogenic Potential ◽  
Cytotoxic Effects ◽  
Content Type ◽  
Group Species

ABSTRACT Gram-positive, spore-forming members of the Bacillus cereus group species complex are widespread in natural environments and display various degrees of pathogenicity. Recently, B. cereus group strain Bacillus mycoides Flugge ATCC 21929 was found to represent a novel lineage within the species complex, sharing a relatively low degree of genomic similarity with all B. cereus group genomes (average nucleotide identity [ANI] < 88). ATCC 21929 has been previously associated with the production of a patented antibiotic, antibiotic 60-6 (i.e., cerexin A); however, the virulence potential and growth characteristics of this lineage have never been assessed. Here, we provide an extensive genomic and phenotypic characterization of ATCC 21929, and we assess its pathogenic potential in vitro. ATCC 21929 most closely resembles Bacillus paramycoides NH24A2T (ANI and in silico DNA-DNA hybridization values of 86.70 and 34.10%, respectively). Phenotypically, ATCC 21929 does not possess cytochrome c oxidase activity and is able to grow at a range of temperatures between 15 and 43°C and a range of pH between 6 and 9. At 32°C, ATCC 21929 shows weak production of diarrheal enterotoxin hemolysin BL (Hbl) but no production of nonhemolytic enterotoxin (Nhe); at 37°C, neither Hbl nor Nhe is produced. Additionally, at 37°C, ATCC 21929 does not exhibit cytotoxic effects toward HeLa cells. With regard to fatty acid composition, ATCC 21929 has iso-C17:0 present in highest abundance. Based on the characterization provided here, ATCC 21929T (= PS00077AT = PS00077BT = PSU-0922T = BHPT) represents a novel effective B. cereus group species, which we propose as effective species “Bacillus clarus.” IMPORTANCE The B. cereus group comprises numerous closely related lineages with various degrees of pathogenic potential and industrial relevance. Species-level taxonomic classification of B. cereus group strains is important for risk evaluation and communication but remains challenging. Biochemical and phenotypic assays are often used to assign B. cereus group strains to species but are insufficient for accurate taxonomic classification on a genomic scale. Here, we show that antibiotic-producing ATCC 21929 represents a novel lineage within the B. cereus group that, by all metrics used to delineate prokaryotic species, exemplifies a novel effective species. Furthermore, we show that ATCC 21929 is incapable of producing enterotoxins Hbl and Nhe or exhibiting cytotoxic effects on HeLa cells at human body temperature in vitro. These results provide greater insight into the genomic and phenotypic diversity of the B. cereus group and may be leveraged to inform future public health and food safety efforts.

scholarly journals In VitroCombination of Isavuconazole with Micafungin or Amphotericin B Deoxycholate against Medically Important Molds

2014 ◽  
Vol 58 (11) ◽  
pp. 6934-6937 ◽  
Author(s):  
Aspasia Katragkou ◽  
Matthew McCarthy ◽  
Joseph Meletiadis ◽  
Vidmantas Petraitis ◽  
Patriss W. Moradi ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Aspergillus Flavus ◽  
Aspergillus Terreus ◽  
Synergistic Activity ◽  
Content Type ◽  
Amphotericin B Deoxycholate ◽  
Combination Studies

ABSTRACTWhether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Ourin vitrocombination studies showed that isavuconazole and micafungin are synergistically active againstAspergillus fumigatus,Aspergillus flavus,Aspergillus terreus, andCunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation.

scholarly journals New Insight into Amphotericin B Resistance in Aspergillus terreus

2013 ◽  
Vol 57 (4) ◽  
pp. 1583-1588 ◽  
Author(s):  
Gerhard Blum ◽  
Caroline Hörtnagl ◽  
Emina Jukic ◽  
Thomas Erbeznik ◽  
Thomas Pümpel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Molecular Basis ◽  
Aspergillus Terreus ◽  
Minor Role ◽  
Content Type ◽  
Ergosterol Content ◽  
Disseminated Aspergillosis ◽  
A Minor

ABSTRACTAmphotericin B (AMB) is the predominant antifungal drug, but the mechanism of resistance is not well understood. We compared thein vivovirulence of an AMB-resistantAspergillus terreus(ATR) isolate with that of an AMB-susceptibleA. terreusisolate (ATS) using a murine model for disseminated aspergillosis. Furthermore, we analyzed the molecular basis of intrinsic AMB resistancein vitroby comparing the ergosterol content, cell-associated AMB levels, AMB-induced intracellular efflux, and prooxidant effects between ATR and ATS. Infection of immunosuppressed mice with ATS or ATR showed that the ATS strain was more lethal than the ATR strain. However, AMB treatment improved the outcome in ATS-infected mice while having no positive effect on the animals infected with ATR. Thein vitrodata demonstrated that ergosterol content is not the molecular basis for AMB resistance. ATR absorbed less AMB, discharged more intracellular compounds, and had better protection against oxidative damage than the susceptible strain. Our experiments showed that ergosterol content plays a minor role in intrinsic AMB resistance and is not directly associated with intracellular cell-associated AMB content. AMB might exert its antifungal activity by oxidative injury rather than by an increase in membrane permeation.

scholarly journals Pharmacokinetics of LFF571 and Vancomycin in Patients with Moderate Clostridium difficile Infections

2014 ◽  
Vol 59 (3) ◽  
pp. 1441-1445 ◽  
Author(s):  
Suraj G. Bhansali ◽  
Kathleen Mullane ◽  
Lillian S. L. Ting ◽  
Jennifer A. Leeds ◽  
Kristina Dabovic ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Diarrheal Disease ◽  
Systemic Exposure ◽  
Serum Levels ◽  
Controlled Study ◽  
Content Type ◽  
Drug Concentrations ◽  
End Of Treatment ◽  
To Receive

ABSTRACTClostridium difficileinfection causes diarrheal disease with potentially fatal complications. Although treatments are available, including vancomycin, metronidazole, and fidaxomicin, the recurrence of disease after therapy remains a problem. LFF571 is a novel thiopeptide antibacterial that showsin vitropotency againstC. difficilethat is comparable to or greater than that of other clinically used antibiotics. Here, we compare the pharmacokinetics (PK) of LFF571 and vancomycin in patients withC. difficileinfection as part of an early efficacy study. This multicenter, randomized, evaluator-blind, and active-controlled study evaluated the safety, efficacy, and pharmacokinetics of LFF571 in adults with primary episodes or first relapses of moderateC. difficileinfections. Patients were randomized to receive 200 mg of LFF571 or 125 mg of vancomycin four times daily for 10 days. The PK parameters were calculated from drug concentrations measured in serum and fecal samples. The systemic exposure following oral administration of 200 mg of LFF571 four times per day for 10 days in patients withC. difficileinfection was limited. The highest LFF571 serum concentration observed was 41.7 ng/ml, whereas the levels in feces at the end of treatment were between 107 and 12,900 μg/g. In comparison, the peak vancomycin level observed in serum was considerably higher, at 2.73 μg/ml; the levels of vancomycin in feces were not measured. Similar to healthy volunteers, patients withC. difficileinfections exhibited high fecal concentrations and low serum levels of LFF571. These results are consistent with the retention of LFF571 in the lumen of the gastrointestinal tract. (This study has been registered at ClinicalTrials.gov under registration no. NCT01232595.)

scholarly journals Experimental Therapy with Azoles against Candida guilliermondii

2014 ◽  
Vol 58 (10) ◽  
pp. 6255-6257 ◽  
Author(s):  
Marta Sanchis ◽  
Francisco Javier Pastor ◽  
Javier Capilla ◽  
Deanna A. Sutton ◽  
Annette W. Fothergill ◽  
...  
Keyword(s):  
Murine Model ◽  
Serum Levels ◽  
Candida Guilliermondii ◽  
Experimental Therapy ◽  
Content Type ◽  
Fungal Burden ◽  
Disseminated Candidiasis ◽  
Killing Activity ◽  
Fungistatic Activity

ABSTRACTWe evaluated thein vitrokilling activity of voriconazole (VRC) and posaconazole (PSC) against two clinical isolates ofCandida guilliermondii. The two drugs showed fungistatic activity against both isolates and were effective in reducing kidney fungal burden in a neutropenic murine model of disseminated candidiasis in infected mice. PSC was significantly more effective than VRC against one of the strains. The serum levels of PSC and VRC were above the corresponding MICs for these isolates.

scholarly journals Rifampin Enhances the Activity of Amphotericin B against Fusarium solani Species Complex and Aspergillus flavus Species Complex Isolates from Keratitis Patients

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Yi He ◽  
Lutan Zhou ◽  
Chuanwen Gao ◽  
Lei Han ◽  
Yan Xu
Keyword(s):  
Amphotericin B ◽  
Aspergillus Flavus ◽  
Fusarium Solani ◽  
Species Complex ◽  
Content Type ◽  
Fusarium Solani Species Complex ◽  
Fungal Isolates

ABSTRACT The in vitro activities of amphotericin B in combination with rifampin were assessed against 95 ocular fungal isolates. The interactions between amphotericin B and rifampin at 4, 8, 16, and 32 μg/ml were synergistic for 11.8%, 51.0%, 90.2%, and 94.1%, respectively, of Fusarium solani species complex isolates and for 13.6%, 45.5%, 93.2%, and 95.5%, respectively, of Aspergillus flavus species complex isolates. Antagonism was never observed for the amphotericin B-rifampin combinations.

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