Orphan designation: Amphotericin B (for inhalation use), Prevention of pulmonary fungal infection in patients deemed at risk

2019 ◽  
Author(s):  
Keyword(s):  
At Risk ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Orphan Designation

scholarly journals Coccidioidomycosis: a review

2021 ◽  
Vol 69 (2) ◽  
pp. 316-323
Author(s):  
Royce H Johnson ◽  
Rupam Sharma ◽  
Rasha Kuran ◽  
Isabel Fong ◽  
Arash Heidari
Keyword(s):  
Fungal Infection ◽  
Amphotericin B ◽  
Western Hemisphere ◽  
Disease Treatment ◽  
Small Minority ◽  
Severe Infections ◽  
Disseminated Disease

Coccidioidomycosis is a fungal infection of the Western hemisphere that is endemic to the soil in areas with limited rainfall. Human and animal infections result with inhalation of arthroconidia. Most often, this is an asymptomatic event. When illness occurs, it is primarily a pneumonic presentation. A small minority of infections eventuate in disseminated disease. Predominately, this presents as meningitis or osteoarticular or integumentary disease. Treatment may not be required for the mildest illness. Azoles are commonly prescribed. Severe infections may require amphotericin B.

scholarly journals Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections

2021 ◽  
Author(s):  
Alyaa A. Albadr ◽  
Ismaiel A. Tekko ◽  
Lalitkumar K. Vora ◽  
Ahlam A. Ali ◽  
Garry Laverty ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Significant Inhibition ◽  
Corneal Tissue ◽  
Biodegradable Poly ◽  
Invasive Method ◽  
Poorly Soluble ◽  
Microneedle Patch

AbstractChronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)–based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays’ reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch. Graphical abstract

Aspergillus terreus Species Complex

2021 ◽  
Author(s):  
Cornelia Lass-Flörl ◽  
Anna-Maria Dietl ◽  
Dimitrios P. Kontoyiannis ◽  
Matthias Brock
Keyword(s):  
At Risk ◽  
Aspergillus Fumigatus ◽  
Human Health ◽  
Amphotericin B ◽  
Species Complex ◽  
Aspergillus Terreus ◽  
Clinical Spectrum ◽  
Chronic Infections ◽  
Epidemiological Surveys ◽  
Risk Patients

Infections due to Aspergillus species are an acute threat to human health; members of the Aspergillus section Fumigati are the most frequently occurring agents, but depending on the local epidemiology, representatives of section Terrei or section Flavi are the second or third most important. Aspergillus terreus species complex is of great interest, as it is usually amphotericin B resistant and displays notable differences in immune interactions in comparison to Aspergillus fumigatus . The latest epidemiological surveys show an increased incidence of A. terreus as well as an expanding clinical spectrum (chronic infections) and new groups of at-risk patients being affected.

scholarly journals Itraconazole Oral Solution for Primary Prophylaxis of Fungal Infections in Patients with Hematological Malignancy and Profound Neutropenia: a Randomized, Double-Blind, Double-Placebo, Multicenter Trial Comparing Itraconazole and Amphotericin B

2000 ◽  
Vol 44 (7) ◽  
pp. 1887-1893 ◽  
Author(s):  
J. L. Harousseau ◽  
A. W. Dekker ◽  
A. Stamatoullas-Bastard ◽  
A. Fassas ◽  
W. Linkesch ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Hematological Malignancy ◽  
Fungal Infections ◽  
Treated Group ◽  
Multicenter Trial ◽  
Oral Solution ◽  
Double Blind ◽  
Systemic Fungal Infection

ABSTRACT Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 × 109 neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%];P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.

Antifungal stewardship

2016 ◽  
Author(s):  
Laura Whitney ◽  
Tihana Bicanic
Keyword(s):  
At Risk ◽  
Fungal Infection ◽  
Antibiotic Stewardship ◽  
Evidence Base ◽  
Antifungal Stewardship ◽  
Population At Risk

Although the principles of antifungal stewardship are similar to those of antibiotic stewardship, there are a number of key differences, as outlined in this chapter. Antifungal prescribing occupies a specialist niche: it occurs much less frequently than antibacterial prescribing due to the smaller, but increasing, population at risk of fungal infection. Antifungal stewardship is thus less established compared with programmes directed at antibacterials, with a narrower and more complex evidence base. This chapter provides examples of successful stewardship programmes in different settings, allowing readers to understand the challenges of antifungal stewardship and how to address these and enabling them to build a successful stewardship programme at their own institution.

Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia

1993 ◽  
Vol 31 (6) ◽  
pp. 973-984 ◽  
Author(s):  
J. N. Philpott-Howard ◽  
J. J. Wade ◽  
G. J. Mufti ◽  
K. W. Brammer ◽  
G. Ehniniger
Keyword(s):  
At Risk ◽  
Fungal Infection ◽  
Oral Fluconazole ◽  
Patients At Risk

scholarly journals Involvement of host macrophages in the immunoadjuvant activity of amphotericin B in a mouse fungal infection model.

1986 ◽  
Vol 39 (6) ◽  
pp. 846-855 ◽  
Author(s):  
A. VECCHIARELLI ◽  
G. VERDUCCI ◽  
S. PERITO ◽  
P. PUCCETTI ◽  
P. MARCONI ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Amphotericin B ◽  
Infection Model

Empiric Antifungal Therapy with Amphotericin B in the Era of Fluconazole Prophylaxis: a Cohort Study in Adults with Acute Myeloid Leukemia Treated within An Institutional Antifungal Policy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1390-1390
Author(s):  
Anita Adams ◽  
Tamana Hafid ◽  
Kari Kolm ◽  
Jolanta Jeziorowska ◽  
Deborah C Marcellus ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Induction Chemotherapy ◽  
Antifungal Therapy ◽  
Empiric Therapy ◽  
Best Supportive Care ◽  
Antifungal Prophylaxis ◽  
Second Line ◽  
Fluconazole Prophylaxis

Abstract Abstract 1390 Poster Board I-412 Purpose: To determine whether fluconazole prophylaxis was effective in decreasing the need for parenteral empiric antifungal therapy in patients with acute myeloid leukemia (AML) and persistent febrile neutropenia or suspected fungal infection at our center. Background: Prophylaxis with fluconazole in patients with severe chemotherapy-related neutropenia has been found to be beneficial in decreasing the need for parenteral antifungal therapy, and preventing superficial and invasive fungal infections and fungal infection-related mortality (Bow et al., Cancer 2002;94:3230-3246). Methods: The records of all patients at our hospital who presented with AML from January 1999 to July 2009 were reviewed retrospectively. As of September 2005 we adopted an institutional antifungal policy consisting of routine antifungal prophylaxis with fluconazole followed by amphotericin B as the first line parenteral agent in the event of persistent fever despite broad spectrum antibiotics or suspected fungal infection. The policy included criteria for switching from amphotericin B to a second line agent (caspofungin) for continued empiric therapy or another agent depending on clinical or laboratory data or suspicion of a particular pathogen. Explicit criteria were also developed for switching to a second line agent including baseline renal function or change in renal function while receiving amphotericin B or other adverse effects such as significant infusion reactions or electrolyte disturbances. Fluconazole was given at a dose of 400 mg daily starting with induction chemotherapy and continued until blood count recovery or switch to parenteral antifungal agent. Results: We identified a total of 170 patients with a median age of 61 years (range 18-89 years), 53 % were female and the median follow-up time was 187 days (range 2-2549 days). Baseline cytogenetics grouped patients into poor risk (40%), standard risk (39%) and favorable risk (10%) categories, with 11% unknown or inconclusive. Two-thirds of patients had de-novo AML. Twenty-four percent of patients did not receive induction chemotherapy and were treated with best supportive care, leaving 130 patients who received induction chemotherapy. Overall median survival for chemotherapy treated patients was 409 days, compared with 44 days for patients treated with best supportive care. The majority of patients (77%) who received chemotherapy were treated with standard induction consisting of 3 days of an anthracycline and 7-10 days of continuous infusion cytarabine. Of the patients treated with induction chemotherapy, 65% received prophylaxis with fluconazole and 32% did not, the remainder received prophylaxis with other antifungal agents. The use of prophylactic fluconazole coincided with implementation of our antifungal policy. Of patients who were treated with fluconazole prophylaxis, 62% required parenteral antifungal therapy and 38% did not. Of patients who did not receive fluconazole prophylaxis 56% required parenteral antifungals and 44% did not. These differences relating to receiving fluconazole prophylaxis were not statistically significantly different. For those patients requiring empiric antifungal therapy, they received a median of 18 days of fluconazole (range 3-156 days). Of the 56 patients who were treated with amphotericin B as empiric therapy, 59% were changed to another agent due to renal effects (42%), fever (27%) or other adverse effects (21%). Switching off amphotericin B occurred after a median of 7.5 days (range 0-59 days). Fifty-six percent of patients received caspofungin as the second line agent while the policy was in effect. Conclusion: Based on our retrospective analysis of the practical use of antifungal prophylaxis within our institutional antifungal policy, fluconazole prophylaxis did not decrease the need for empiric parenteral antifungal therapy. The majority of patients treated with empiric amphotericin B were switched to a second line agent, mostly due to intolerance or adverse effects. Disclosures: No relevant conflicts of interest to declare.

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.

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