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BMC Infectious Diseases Apr 2024In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with...
BACKGROUND
In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections.
METHODS
We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023.
RESULTS
Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects.
CONCLUSION
The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.
Topics: Humans; Amphotericin B; Male; Female; Retrospective Studies; Middle Aged; Antifungal Agents; Aged; Administration, Topical; Adult; Treatment Outcome; Respiratory Tract Infections; Aged, 80 and over; Lung Diseases, Fungal; Young Adult
PubMed: 38658844
DOI: 10.1186/s12879-024-09342-9 -
Frontiers in Cellular and Infection... 2020The design and development of new pharmaceutical formulations for the existing anti-leishmanial is a new strategic alternate to improve efficacy and safety rather than...
Recuperating Biopharmaceutical Aspects of Amphotericin B and Paromomycin Using a Chitosan Functionalized Nanocarrier via Oral Route for Enhanced Anti-leishmanial Activity.
The design and development of new pharmaceutical formulations for the existing anti-leishmanial is a new strategic alternate to improve efficacy and safety rather than new drug discovery. Herein hybrid solid lipid nanoparticles (SLN) have been engineered to direct the oral delivery of two anti-leishmanial drugs amphotericin B (AmB) and paromomycin (PM). The combinatorial nanocarriers consist of conventional SLN, antileishmanial drugs (AmB and PM) which have been functionalized with chitosan (Cs) grafted onto the external surface. The Cs-SLN have the mean particle size of 373.9 ± 1.41 nm, polydispersity index (PDI) of 0.342 ± 0.02 and the entrapment efficiency for AmB and PM was found to be 95.20 ± 3.19% and 89.45 ± 6.86 %, respectively. Characterization of SLN was performed by scanning electron microscopy and transmission electron microscopy. Complete internalization of the formulation was observed in Caco-2 cells. Cs-SLN has shown a controlled and slow drug release profile over a period of 72 h and was stable at gastrointestinal fluids, confirmed by simulated gastro-intestinal fluids study. Cs coating enhanced the mucoadhesive property of Cs-SLN. anti-leishmanial activity of Cs-SLN (1 μg/ml) has shown a maximum percentage of inhibition (92.35%) on intra-cellular amastigote growth of .
Topics: Amphotericin B; Biological Products; Caco-2 Cells; Chitosan; Drug Carriers; Humans; Nanoparticles; Paromomycin; Particle Size
PubMed: 33178626
DOI: 10.3389/fcimb.2020.570573 -
PloS One 2023A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess...
A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-β) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.
Topics: Leishmania major; Amphotericin B; Molecular Docking Simulation; Carotenoids
PubMed: 37682934
DOI: 10.1371/journal.pone.0291322 -
Pathogens and Global Health May 2012
Review
Topics: Amphotericin B; Antifungal Agents; Fungi; Humans; Mycoses
PubMed: 22943542
DOI: 10.1179/204777312X13419245939566 -
Postgraduate Medical Journal Sep 1979The absorption of flucytosine from the digestive tract is very good but minimal with amphotericin B. For this reason, amphotericin B has to be injected intravenously....
The absorption of flucytosine from the digestive tract is very good but minimal with amphotericin B. For this reason, amphotericin B has to be injected intravenously. Fungistatic levels are achieved rapidly with flucytosine and slowly with amphotericin B, since the dose has to be increased slowly. Distribution of flucytosine in other body fluids is high, whereas with amphotericin B it is poor. Flucytosine is excreted mainly via the kidney without metabolism, whereas amphotericin B is eliminated mainly by metabolism. Therefore, amphotericin B dosage does not have to be adapted to kidney function, which is the case for flucytosine. The half-life of flucytosine is short (hours), that of amphotericin B is long (days); flucytosine is haemodialysable, whereas amphotericin B, probably owing to the high protein binding, is not.
Topics: Amphotericin B; Animals; Cytosine; Drug Administration Schedule; Flucytosine; Half-Life; Humans; Kinetics; Models, Biological; Rabbits; Renal Dialysis
PubMed: 523358
DOI: 10.1136/pgmj.55.647.667 -
Molecules (Basel, Switzerland) Jun 2023During the COVID-19 pandemic, the treatment of pulmonary fungal infection faced noteworthy challenges. Amphotericin B has shown promising therapeutic effects as an...
During the COVID-19 pandemic, the treatment of pulmonary fungal infection faced noteworthy challenges. Amphotericin B has shown promising therapeutic effects as an inhalation treatment for pulmonary fungal infections, especially those associated with the COVID-19 virus, due to its rare resistance. However, because the drug frequently produces renal toxicity, its effective dose is limited in clinical use. In this work, the DPPC/DPPG mixed monolayer was used as the pulmonary surfactant monolayer to study the interaction between amphotericin B and the pulmonary surfactant monolayer during inhalation therapy using the Langmuir technique and atomic force microscopy. The effects of different molar ratios of AmB on the thermodynamic properties and surface morphology of the pulmonary surfactant monolayer at different surface pressures was evaluated. The results showed that when the molar ratio of AmB to lipids in the pulmonary surfactant was less than 1:1, the main intermolecular force was attractive at a surface pressure greater than 10 mN/m. This drug had little effect on the phase transition point of the DPPC/DPPG monolayer, but decreased the height of the monolayer at 15 mN/m and 25 mN/m. When the molar ratio of AmB to lipids was greater than 1:1, the intermolecular force was mainly repulsive at a surface pressure greater than 15 mN/m, and AmB increased the height of the DPPC/DPPG monolayer at both 15 mN/m and 25 mN/m. These results are helpful in understanding the interaction between the pulmonary surfactant model monolayer and different doses of drugs at various surface tensions during respiration.
Topics: Humans; Pulmonary Surfactants; Amphotericin B; 1,2-Dipalmitoylphosphatidylcholine; Pandemics; COVID-19; Respiration; Surface Properties
PubMed: 37375395
DOI: 10.3390/molecules28124840 -
Environmental Science and Pollution... Jan 2023COVID-19 disease has been identified to cause remarkable increase of mucormycosis infection cases in India, with the majority of cases being observed in individuals... (Review)
Review
COVID-19 disease has been identified to cause remarkable increase of mucormycosis infection cases in India, with the majority of cases being observed in individuals recovering from COVID-19. Mucormycosis has emanated as an outcome of the recent COVID-19 pandemic outbreak as rapidly developing fatal illness which was acquired by Mucorales fungus which is a subcategory of molds known as mucormycetes. Mucormycosis is one of the serious, sporadic mycotic illnesses which is a great threat to immunocompromised COVID-19 patients and affects people of all ages, including children with COVID-19 infections. This is associated with tissue damaging property and, therefore, causes serious clinical complications and elevated death rate. The COVID-19-associated mucormycosis or "black fungus" are the terms used interchangeably. The rapid growth of tissue necrosis presenting as "rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated disease" are various clinical forms of mucormycosis. The patient's prognosis and survival can be improved with proper surgeries using an endoscopic approach for local tissue protection in conjunction with course of appropriate conventional antifungal drug like Amphotericin-B and novel drugs like Rezafungin, encochleated Amphotericin B, Orolofim, and SCY-078 which have been explored in last few years. This review provides an overview of mucormycosis including its epidemiology, pathophysiology, risk factors, its clinical forms, and therapeutic approaches for disease management like antifungal therapy, surgical debridement, and iron chelators. The published patents and ongoing clinical trials related to mucormycosis have also been mentioned in this review.
Topics: Child; Humans; Mucormycosis; Antifungal Agents; Pandemics; COVID-19; Amphotericin B
PubMed: 36454526
DOI: 10.1007/s11356-022-24032-2 -
Antimicrobial Agents and Chemotherapy Jun 1975The comparative efficacy of amphotericin B and amphotericin B methyl ester (AME) against experimental histoplasmosis, blastomycosis, cryptococcosis, and candidosis in... (Comparative Study)
Comparative Study
The comparative efficacy of amphotericin B and amphotericin B methyl ester (AME) against experimental histoplasmosis, blastomycosis, cryptococcosis, and candidosis in mice was assessed by determining the effect of daily intraperitoneal therapy on 21-day survival and persistence of organisms in internal organs. AME, like amphotericin B, was effective against each of the experimental infections, but the efficacy was lower than the parent compound. For Histoplasma and Blastomyces infections the mean effective dose (ED(50)) of amphotericin B was 0.3 mg/kg, whereas the corresponding values for AME, respectively, were 2.4 and 2.8 mg/kg. For Cryptococcus infection the ED(50) for amphotericin B was 0.2 mg/kg compared with 2.0 mg/kg for AME. The ED(50) of amphotericin B for Candida infection was lower than 0.05 mg/kg and the value of AME was between 0.5 to 0.05 mg/kg. The colony counts from internal organs of the surviving animals after the therapeutic regimens were compatible with the data on survival.
Topics: Amphotericin B; Animals; Blastomycosis; Candidiasis; Cryptococcosis; Esters; Histoplasmosis; Male; Mice
PubMed: 1155916
DOI: 10.1128/AAC.7.6.724 -
The American Journal of Tropical... Feb 2023This study describes the microbiological and histopathological features of patients with COVID-19-associated rhino-orbital mucormycosis (ROM) seen at the L V Prasad Eye...
This study describes the microbiological and histopathological features of patients with COVID-19-associated rhino-orbital mucormycosis (ROM) seen at the L V Prasad Eye Institute between May and August 2021. Diagnosed clinically and radiologically, 24 patients with ROM were included in the study. Deep nasal swabs or endoscopically collected nasal swabs or orbital tissues were submitted for microbiological evaluation and in vitro susceptibility testing by microbroth dilution for natamycin, amphotericin B, caspofungin, posaconazole, ketoconazole, and voriconazole. Cultures were processed by 28S ribosomal DNA polymerase chain reaction and molecular sequencing. A portion of orbital tissues was also sent for histopathological evaluation. The age of the patients ranged from 27 to 75 (mean 48.58 ± 14.09) years and the majority (79%) were male. Nineteen patients were known to be diabetic prior to developing ROM and 18 patients had recovered from active COVID-19 infection. Thirteen patients had a history of hospitalization during COVID-19 infection and eight received steroids. Of the 24 samples, microbiological evaluation identified Rhizopus arrhizus in 12, Rhizopus microsporus in 9, Lichtheimia ramosa in 2, and Rhizopus delemar in 1. Twelve isolates were tested for antifungal susceptibility and all were susceptible to natamycin and amphotericin B. The susceptibility to posaconazole was high, with minimum inhibitory concentration (MIC) < 2 µg/mL for 10/12 (84%) isolates, whereas the MIC of other drugs varied. Histopathological examination of tissues showed acute fulminant disease, granuloma formation, and vascular invasion by the fungal pathogens in these specimens. Rhizopus arrhizus was predominantly associated with ROM and most isolates were susceptible to amphotericin B and posaconazole. Further studies are needed to corroborate the findings and explain possible underlying links.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Mucormycosis; Amphotericin B; Natamycin; COVID-19; Antifungal Agents; Eye Diseases; Rhizopus oryzae; India
PubMed: 36572009
DOI: 10.4269/ajtmh.22-0411 -
Cleveland Clinic Journal of Medicine Sep 1998Amphotericin B has long been the mainstay in the treatment of systemic fungal infections, but its nephrotoxicity limits the dosage that can be used. New lipid-based... (Review)
Review
Amphotericin B has long been the mainstay in the treatment of systemic fungal infections, but its nephrotoxicity limits the dosage that can be used. New lipid-based forms may allow higher dosing with less nephrotoxicity. Unfortunately, these new forms are substantially more expensive, and data from randomized clinical trials of their relative efficacy are as yet limited.
Topics: Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Clinical Trials as Topic; Costs and Cost Analysis; Dose-Response Relationship, Drug; Drug Carriers; Humans; Infusions, Intravenous; Kidney; Lipids; Mycoses; Tissue Distribution
PubMed: 9769563
DOI: 10.3949/ccjm.65.8.423