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Viruses Jun 2022Hepatitis E virus (HEV) infection in humans is primarily caused by genotypes within species (HEV-A). species (HEV-C1, otherwise known as rat HEV) can also infect...
Hepatitis E virus (HEV) infection in humans is primarily caused by genotypes within species (HEV-A). species (HEV-C1, otherwise known as rat HEV) can also infect humans. HEV grows poorly in cell culture. Recent studies have reported that hyper-confluent cell layers, amphotericin B, MgCl, progesterone, and dimethyl sulfoxide (DMSO) increase HEV yield in vitro. Here, we describe an independent evaluation of the effectiveness of these modifications in improving the yield of HEV-A genotype 4 (HEV-A4) and HEV-C1 from clinical samples in PLC/PRF/5 cells. We found that amphotericin B, MgCl, and DMSO increased HEV yield from high-viral-load patient stool samples, while progesterone was not effective. Yield of HEV-C1 was lower than HEV-A4 across all medium conditions, but was boosted by DMSO. HEV-A4 could be maintained for over 18 months in amphotericin B- and MgCl-containing medium, with the demonstration of viral antigen in supernatants and infected cells. We also evaluated various protocols to remove pseudo-envelopes from cell culture-derived HEV. Treating cell culture supernatant with NP-40 was the most effective. Our findings identify key modifications that boost HEV growth in vitro and illustrate the importance of independent verification of such studies using diverse HEV variants and cell lines.
Topics: Amphotericin B; Animals; Cell Culture Techniques; Dimethyl Sulfoxide; Hepatitis E; Hepatitis E virus; Humans; Rats
PubMed: 35746725
DOI: 10.3390/v14061254 -
Indian Journal of Ophthalmology Sep 2023To curtail the potential of donor corneal tissue disseminating fungi to the recipient's eye, we evaluated the addition of amphotericin B to McCarey-Kaufman (M-K)-corneal...
PURPOSE
To curtail the potential of donor corneal tissue disseminating fungi to the recipient's eye, we evaluated the addition of amphotericin B to McCarey-Kaufman (M-K)-corneal storage medium supplemented with colistin.
METHODS
Amphotericin B was examined for its ability to inhibit the growth of Candida albicans and Aspergillus flavus using a microbroth dilution test and checkerboard assay in combination with only gentamicin and a combination of colistin, gentamicin, and amphotericin B. The safety on epithelium and endothelium was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
RESULTS
The minimal inhibitory concentration of gentamicin was found to be >256 μg/ml against both C. albicans and A. flavus, whereas that of amphotericin B was found to be in a range of 0.25-0.5 and 1-2 μg/ml for C. albicans and A. flavus, respectively. According to the checkerboard assay, 80% (4/5) of C. albicans isolates and 100% (5/5) of A. flavus isolates responded synergistically to the combination of amphotericin B and gentamicin, but only 20% (1/5) of C. albicans isolates showed an additive effect. None of the tested isolates displayed antagonism. The combined effect of the three drugs also did not display any antagonistic effect. Additionally, the MTT assay reveals no toxic effect of the antimicrobials used on corneal epithelial and endothelial cells.
CONCLUSION
In vitro experiments demonstrate that amphotericin B is not toxic to either epithelium or endothelium and is a promising additive to the M-K medium supplemented with colistin.
Topics: Humans; Amphotericin B; Colistin; Endothelial Cells; Gentamicins
PubMed: 37602602
DOI: 10.4103/IJO.IJO_455_23 -
Emerging Microbes & Infections Dec 2024The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B...
The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B against multidrug-resistant Candida auris. The authors administered lansoprazole at concentrations significantly higher than typical therapeutic doses, which demonstrated promising results but also raised concerns about potential toxicity. We suggest incorporating a control group, monitoring toxicity indicators, performing pathological examinations, and conducting cellular assays to improve the study's rigor and reliability. We also highlight the need for further research into the mechanisms of lansoprazole's antifungal activity, its long-term effects on amphotericin B resistance, and potential drug-drug interactions with amphotericin B. Addressing these concerns is crucial for the clinical translation of lansoprazole as an adjuvant to amphotericin B.
Topics: Lansoprazole; Amphotericin B; Antifungal Agents; Drug Resistance, Multiple, Fungal; Drug Synergism; Microbial Sensitivity Tests; Humans; Candida auris; Candidiasis; Proton Pump Inhibitors
PubMed: 38742537
DOI: 10.1080/22221751.2024.2356144 -
Ear, Nose, & Throat Journal Jun 2024Mucormycosis is almost always confined to the patients with altered host defenses amongst which diabetes is considered as the strongest risk factor. COVID-19 only been...
Mucormycosis is almost always confined to the patients with altered host defenses amongst which diabetes is considered as the strongest risk factor. COVID-19 only been seen in severe cases but also in mild and moderate cases of SARS-CoV-2 infections. After preliminary clinical and radiological diagnosis, surgical management in the form of endoscopic sinus surgery, debridement, and orbital exenteration (8) was performed. Medical management in the form of antifungal therapy (amphotericin-B, posaconazole, and isavuconazole) was initiated. In this case series, 79 proven cases of COVID-19 associated rhino-orbital-cerebral mucormycosis were analyzed retrospectively from mid-April 2021 to mid-September 2021. 67 patients were known diabetics, whereas rest 12 had new onset diabetes mellitus. Of these 79 cases, 27 cases had the disease limited to sinuses (rhino-mucormycosis), 43 had orbital involvement also (rhino-orbital mucormycosis), and 9 had cerebral involvement as well (rhino-orbital-cerebral mucormycosis). During this time-period, a total of 14 mortalities occurred. Most of the patients were discharged after completion of amphotericin-B therapy and rest stayed little longer till their general condition improved. COVID-19 causes dysregulation and alteration of immune response in the body which predispose to invasive fungal infections. In addition, uncontrolled diabetes mellitus and corticosteroid treatment increase the risk of mucormycosis by many folds.
Topics: Humans; Mucormycosis; COVID-19; Male; Female; Middle Aged; Retrospective Studies; Antifungal Agents; Aged; Adult; Orbital Diseases; SARS-CoV-2; Amphotericin B; Debridement; Triazoles
PubMed: 35176884
DOI: 10.1177/01455613221077882 -
PLoS Neglected Tropical Diseases Jun 2024In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh.
BACKGROUND
In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.
CONCLUSIONS/SIGNIFICANCE
Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.
TRIAL REGISTRATION
CTRI/2017/04/008421.
Topics: Humans; Amphotericin B; Phosphorylcholine; Bangladesh; Male; Antiprotozoal Agents; Adult; Adolescent; Female; Middle Aged; Young Adult; Child; India; Leishmaniasis, Visceral; Treatment Outcome; Leishmaniasis, Cutaneous; Drug Therapy, Combination
PubMed: 38900786
DOI: 10.1371/journal.pntd.0012242 -
Expert Opinion on Pharmacotherapy May 2021: spp. are commensal yeasts capable of causing infections such as superficial, oral, vaginal, or systemic infections. Despite medical advances, the antifungal...
: spp. are commensal yeasts capable of causing infections such as superficial, oral, vaginal, or systemic infections. Despite medical advances, the antifungal pharmacopeia remains limited and the development of alternative strategies is needed.: We discuss available treatments for spp. infections, highlighting advantages and limitations related to pharmacokinetics, cytotoxicity, and antimicrobial resistance. Moreover, we present new perspectives to improve the activity of the available antifungals, discussing their immunomodulatory potential and advances on drug delivery carriers. New therapeutic approaches are presented including recent synthesized antifungal compounds (Enchochleated-Amphotericin B, tetrazoles, rezafungin, enfumafungin, manogepix and arylamidine); drug repurposing using a diversity of antibacterial, antiviral and non-antimicrobial drugs; combination therapies with different compounds or photodynamic therapy; and innovations based on nano-particulate delivery systems.: With the lack of novel drugs, the available assets must be leveraged to their best advantage through modifications that enhance delivery, efficacy, and solubility. However, these efforts are met with continuous challenges presented by microbes in their infinite plight to resist and survive therapeutic drugs. The pharmacotherapeutic options in development need to focus on new antimicrobial targets. The success of each antimicrobial agent brings strategic insights to the next phased approach in treating spp. infections.
Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Female; Humans
PubMed: 33538201
DOI: 10.1080/14656566.2021.1873951 -
Biomedicine & Pharmacotherapy =... Jun 2024The growth of antibiotic resistance to antifungal drugs contributes to the search for new ways to enhance their effectiveness and reduce toxicity. The undeniable...
The growth of antibiotic resistance to antifungal drugs contributes to the search for new ways to enhance their effectiveness and reduce toxicity. The undeniable advantage of polyene macrolide antibiotic amphotericin B (AmB) which ensures low pathogen resistance is its mechanism of action related to the formation of transmembrane pores in target lipid membranes. Here, we investigated the effects of plant flavones, chrysin, wogonin, baicalein, apigenin, scutellarein, luteolin, morin and fisetin on the pore-forming activity of AmB in the sterol-enriched membranes by electrophysiological assays. Сhrysin, wogonin, baicalein, apigenin, scutellarein, and luteolin were shown to decrease the AmB pore-forming activity in the bilayers composed of palmitoyloleylphosphocholine independently of their sterol composition. Morin and fisetin led to the increase and decrease in the AmB pore-forming activity in the ergosterol- and cholesterol-containing bilayers respectively. Differential scanning microcalorimetry of the gel-to-liquid crystalline phase transition of membrane forming lipids, molecular dynamics simulations, and absorbance spectroscopy revealed the possibility of direct interactions between AmB and some flavones in the water and/or in the lipid bilayer. The influence of these interactions on the antibiotic partitioning between aqueous solution and membrane and/or its transition between different states in the bilayer was discussed.
Topics: Amphotericin B; Flavones; Lipid Bilayers; Molecular Dynamics Simulation; Antifungal Agents; Phase Transition
PubMed: 38723514
DOI: 10.1016/j.biopha.2024.116723 -
Medical Mycology Feb 2021Treatment options for Exserohilum rostratum meningoencephalitis and other causes of phaeohyphomycosis of the central nervous system (CNS) are limited, while mortality...
Antifungal efficacy of isavuconazole and liposomal amphotericin B in a rabbit model of Exserohilum rostratum meningoencephalitis: A preclinical paradigm for management of CNS phaeohyphomycosis.
Treatment options for Exserohilum rostratum meningoencephalitis and other causes of phaeohyphomycosis of the central nervous system (CNS) are limited, while mortality and morbidity remain high. We therefore evaluated isavuconazole, a new antifungal triazole in comparison to liposomal amphotericin B (LAMB), in vitro and in the rabbit model of Exserohilum rostratum meningoencephalitis. We hypothesized that isavuconazole alone or in combination with LAMB or micafungin may be alternative options for treatment of CNS phaeohyphomycosis. We therefore investigated the in vitro antifungal activity of isavuconazole alone or in combination with amphotericin B deoxycholate (DAMB) or micafungin and efficacy of treatment with isavuconazole and LAMB in a rabbit model of experimental E. rostratum meningoencephalitis. Combination checkerboard plates were used to determine the minimum inhibitory concentrations, minimal lethal concentrations, fractional inhibitory concentration indices, and Bliss surface analysis of isavuconazole and amphotericin B deoxycholate (DAMB), either alone or in combination. As there were no in vitro synergistic or antagonistic interactions for either combination of antifungal agents against the E. rostratum isolates, in vivo studies were conducted with isavuconazole and LAMB as monotherapies. Rabbits were divided in following groups: treated with isavuconazole at 60 mg/kg/d (ISAV60), LAMB at 5.0 (LAMB5), 7.5 (LAMB7.5), and 10 mg/kg/d (LAMB10), and untreated controls (UC). In ISAV60-, LAMB5-, LAMB7.5-, and LAMB10-treated rabbits, significant reductions of fungal burden of E. rostratum in cerebral, cerebellar, and spinal cord tissues (P < 0.01) were demonstrated in comparison to those of UC. These antifungal effects correlated with significant reduction of CSF (1→3)-β-D-glucan levels vs UC (P < 0.05). These data establish new translational insights into treatment of CNS phaeohyphomycosis.
Topics: Amphotericin B; Animals; Antifungal Agents; Ascomycota; Central Nervous System Diseases; Disease Management; Disease Models, Animal; Drug Therapy, Combination; Female; Humans; Microbial Sensitivity Tests; Nitriles; Phaeohyphomycosis; Pyridines; Rabbits; Triazoles
PubMed: 33313821
DOI: 10.1093/mmy/myaa102 -
Molecules (Basel, Switzerland) May 2022Amphotericin B (AMB) is an antifungal drug used for serious fungal infections. However, AMB has adverse reactions such as nephrotoxicity, which limit the clinical...
Amphotericin B (AMB) is an antifungal drug used for serious fungal infections. However, AMB has adverse reactions such as nephrotoxicity, which limit the clinical application of AMB alone or in combination with other antifungal drugs. Nano or micro drug delivery systems (DDS) have been proven to be effective in reducing the toxic and side effects of drugs. Further, the combination of AMB with other compounds with antifungal activity, such as curcumin (CM), may enhance the synergistic effects. Herein, AMB and CM were co-loaded into porous poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) to prepare AMB/CM-PLGA MPs. The AMB/CM-PLGA MPs showed a remarkably reduced hemolysis (62.2 ± 0.6%) compared to AMB (80.9 ± 1.1%). The nephrotoxicity of AMB/CM-PLGA MPs is significantly lower than that of AMB. In vitro, AMB/CM-PLGA MPs had better inhibitory effects on the adhesion and biofilm formation of compared with AMB. Experiments on mice infected with showed that AMB/CM-PLGA MPs have a better therapeutic effect than AMB in vivo. In summary, AMB/CM-PLGA MPs may be a novel and promising therapeutic candidate for fungal infection.
Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Curcumin; Delayed-Action Preparations; Mice; Nanoparticles; Porosity
PubMed: 35630555
DOI: 10.3390/molecules27103079 -
The Lancet. Microbe Dec 2020
Topics: Amphotericin B; Antifungal Agents; Candida; Candida auris; Echinocandins; Micafungin
PubMed: 35544183
DOI: 10.1016/S2666-5247(20)30194-4