Concomitant Amphotericin B Therapy, Granulocyte Transfusions, and GM-CSF Administration for Disseminated Infection with Fusarium in a Granulocytopenic Patient

1993 ◽  
Vol 16 (4) ◽  
pp. 528-530 ◽  
Author(s):  
R. T. Spielberger ◽  
M. J. Falleroni ◽  
A. J. Coene ◽  
R. A. Larson
Keyword(s):  
Amphotericin B ◽  
Disseminated Infection ◽  
Gm Csf ◽  
Granulocytopenic Patient

Blastomycosis

2020 ◽  
Vol 41 (01) ◽  
pp. 031-041 ◽  
Author(s):  
Ilan S. Schwartz ◽  
Carol A. Kauffman
Keyword(s):  
North America ◽  
Amphotericin B ◽  
Skin Lesions ◽  
Primary Therapy ◽  
Temperature Dependent ◽  
Dimorphic Fungi ◽  
Disseminated Infection ◽  
The Central Nervous System ◽  
Yeast Phase ◽  
Tentative Diagnosis

AbstractBlastomycosis is a serious fungal disease of humans and other mammals caused by environmentally acquired infection with geographically restricted, thermally dimorphic fungi belonging to the genus Blastomyces. The genetic and geographic diversity of these pathogens is greater than previously appreciated. In addition to Blastomyces dermatitidis and the cryptic species Blastomyces gilchristii, which cause blastomycosis in mid-western and various eastern areas of North America, atypical blastomycosis is occasionally caused by Blastomyces helicus in western parts of North America and Blastomyces percursus in Africa. Blastomycosis is acquired by inhalation of the conidia that are produced in the mold phase; in the lungs, temperature-dependent transformation occurs to the yeast phase. In this form, the organism is phagocytized by macrophages and can spread hematogenously to various organs causing disseminated infection. Pulmonary disease is most common and varies from mild, self-limited infection to severe, potentially fatal adult respiratory distress syndrome. Disseminated infection is manifested primarily by skin lesions, but many other organs can be involved. Diagnosis is established by growth of the organism in culture; however, a tentative diagnosis can be made quickly by histopathological identification of the classic yeast form in tissues or by finding Blastomyces antigen in urine or serum. Blastomycosis is treated initially with amphotericin B when the disease is severe, involves the central nervous system, or the host is immunosuppressed. Itraconazole is recommended for primary therapy in mild-to-moderate infection and for step-down therapy after initial amphotericin B treatment. Voriconazole and posaconazole can be used for patients in whom itraconazole is not tolerated.

Treatment and Prophylaxis of Disseminated Infection Due to Candida albicans in Mice with Liposome-Encapsulated Amphotericin B

1983 ◽  
Vol 147 (5) ◽  
pp. 939-945 ◽  
Author(s):  
G. Lopez-Berestein ◽  
R. Mehta ◽  
R. L. Hopfer ◽  
K. Mills ◽  
L. Kasi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Disseminated Infection

scholarly journals Activities of Flucytosine, Fluconazole, Amphotericin B, and Micafungin in a Murine Model of Disseminated Infection by Candida glabrata

2005 ◽  
Vol 49 (11) ◽  
pp. 4757-4759 ◽  
Author(s):  
Marçal Mariné ◽  
Carolina Serena ◽  
Belkys Fernández-Torres ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Candida Glabrata ◽  
Disseminated Infection ◽  
Tissue Burden

ABSTRACT We compared the efficacies of amphotericin B, fluconazole, flucytosine, and micafungin in a systemic murine infection by three isolates of Candida glabrata. Amphotericin B showed the best results, although none of the drugs dramatically reduced mortality or tissue burden in liver or spleen.

scholarly journals Regulation of Fungal Infection by a Combination of Amphotericin B and Peptide 2, a Lactoferrin Peptide That Activates Neutrophils

2004 ◽  
Vol 11 (6) ◽  
pp. 1111-1119 ◽  
Author(s):  
Tetsuro Okamoto ◽  
Toyohiro Tanida ◽  
Benjuan Wei ◽  
Eisaku Ueta ◽  
Tetsuya Yamamoto ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Lethal Dose ◽  
Phosphatidyl Inositol ◽  
Antifungal Drugs ◽  
Histatin 5 ◽  
Gm Csf ◽  
Novel Strategy

ABSTRACT To establish a novel strategy for the control of fungal infection, we examined the antifungal and neutrophil-activating activities of antimicrobial peptides. The duration of survival of 50% of mice injected with a lethal dose of Candida albicans (5 × 108 cells) or Aspergillus fumigatus (1 × 108 cells) was prolonged 3 to 5 days by the injection of 10 μg of peptide 2 (a lactoferrin peptide) and 10 μg of α-defensin 1 for five consecutive days and was prolonged 5 to 13 days by the injection of 0.1 μg of granulocyte-monocyte colony-stimulating factor (GM-CSF) and 0.5 μg of amphotericin B. When mice received a combined injection of peptide 2 (10 μg/day) with amphotericin B (0.5 μg/day) for 5 days after the lethal fungal inoculation, their survival was greatly prolonged and some mice continued to live for more than 5 weeks, although the effective doses of peptide 2 for 50 and 100% suppression of Candida or Aspergillus colony formation were about one-third and one-half those of amphotericin B, respectively. In vitro, peptide 2 as well as GM-CSF increased the Candida and Aspergillus killing activities of neutrophils, but peptides such as α-defensin 1, β-defensin 2, and histatin 5 did not upregulate the killing activity. GM-CSF together with peptide 2 but not other peptides enhanced the production of superoxide (O2 −) by neutrophils. The upregulation by peptide 2 was confirmed by the activation of the O2 −-generating pathway, i.e., activation of large-molecule guanine binding protein, phosphatidyl-inositol 3-kinase, protein kinase C, and p47phox as well as p67phox. In conclusion, different from natural antimicrobial peptides, peptide 2 has a potent neutrophil-activating effect which could be advantageous for its clinical use in combination with antifungal drugs.

scholarly journals Efficacy of Triazoles in a Murine Disseminated Infection by Candida krusei

2009 ◽  
Vol 53 (8) ◽  
pp. 3585-3588 ◽  
Author(s):  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Carolina Serena ◽  
Josep Guarro
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Candida Krusei ◽  
Prolonged Survival ◽  
Liposomal Amphotericin B ◽  
Disseminated Infection ◽  
Tissue Burden ◽  
Fungal Tissue

ABSTRACT 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.

scholarly journals Antifungal Activities of Posaconazole and Granulocyte-Macrophage Colony-Stimulating Factor Ex Vivo and in Mice with Disseminated Infection Due to Scedosporium prolificans

2004 ◽  
Vol 48 (10) ◽  
pp. 3801-3805 ◽  
Author(s):  
M. Simitsopoulou ◽  
C. Gil-Lamaignere ◽  
N. Avramidis ◽  
A. Maloukou ◽  
S. Lekkas ◽  
...  
Keyword(s):  
Ex Vivo ◽  
High Rate ◽  
Invasive Infection ◽  
Colony Stimulating Factor ◽  
Disseminated Infection ◽  
Gm Csf ◽  
Scedosporium Prolificans ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT Invasive infection due to Scedosporium prolificans is characterized by drug resistance and a high rate of mortality. The effects of posaconazole (POS), an investigational antifungal triazole, murine granulocyte-macrophage colony-stimulating factor (GM-CSF), and their combination against S. prolificans were evaluated ex vivo and in a newly developed murine model of disseminated infection due to this organism. When POS was combined with polymorphonuclear leukocytes from untreated or GM-CSF-treated mice (P < 0.01) ex vivo, it had increased activity in terms of the percentage of hyphal damage. Immunocompetent BALB/c mice were infected with 4 × 104 conidia of S. prolificans via the lateral tail vein. At 24 h postinfection the mice were treated with GM-CSF (5 μg/kg of body weight/day subcutaneously), POS (50 mg/kg/day by gavage), both agents, or saline only. Half of the brain, lung, liver, and kidney from each animal were cultured; and the other half of each organ was processed for histopathology. The mean survival times were 7.0 ± 0.3 days for the controls, 7.4 ± 0.4 days for POS-treated mice, 8.0 ± 0.3 days for GM-CSF-treated mice (P = 0.08 compared with the results for the controls), and 7.3 ± 0.3 days for POS-GM-CSF-treated mice. Fungal burdens (determined as the numbers of CFU per gram of tissue) were found in descending orders of magnitude in the kidneys, brains, livers, and lungs. The burdens were significantly reduced in the brains of GM-CSF-treated mice (P < 0.05) and the livers of POS-treated mice (P < 0.05). The numbers of lesions in the organs closely corresponded to the fungal burdens. GM-CSF tended to prolong survival (P = 0.08 compared with the results for the controls). While the combination of POS and GM-CSF showed enhanced activity ex vivo, it did not increase the activities of the two agents against this highly refractory filamentous fungus in mice.

scholarly journals Activity of Voriconazole Combined with Neutrophils or Monocytes against Aspergillus fumigatus: Effects of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor

1998 ◽  
Vol 42 (9) ◽  
pp. 2299-2303 ◽  
Author(s):  
Shefali Vora ◽  
Sharda Chauhan ◽  
Elmer Brummer ◽  
David A. Stevens
Keyword(s):  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Hyphal Growth ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT Voriconazole (VCZ) was tested for antifungal activity againstAspergillus fumigatus hyphae alone or in combination with neutrophils or monocytes. Antifungal activity was measured as percent inhibition of hyphal growth in assays using the dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] or XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide]. With both assays, VCZ inhibited hyphal growth at concentrations of <1 μg/ml and was almost as active as amphotericin B. VCZ (0.6 μg/ml) was sporicidal, as was amphotericin B (0.4 μg/ml). With both the MTT and XTT assays, neutrophils alone inhibited hyphae; when combined with VCZ, there was additive activity. Both granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated polymorphonuclear neutrophils (PMN) had enhanced inhibition of hyphal growth. Moreover, such treatment of PMN also enhanced the collaboration of PMN with VCZ. Monocytes inhibited hyphal growth. When VCZ was combined with monocytes or monocytes were treated with GM-CSF, inhibition was significantly increased, to similar levels. However, the combination of VCZ with GM-CSF treatment of monocytes did not significantly increase the high-level inhibition by monocytes with either agent alone.

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