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Antimicrobial Agents and Chemotherapy Dec 2020The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against spp. Visual determination of MICs may be challenging. In this work,...
The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against spp. Visual determination of MICs may be challenging. In this work, we aim to obtain and compare visual and spectrophotometric MIC readings of azoles and amphotericin B against isolates. A total of 847 isolates ( [ = 828] and cryptic species [ = 19]) were tested against amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole using the EUCAST EDef 9.3.2 procedure. Isolates were classified as susceptible or resistant/non-wild type according to the 2020 updated breakpoints. The area of technical uncertainty for the azoles was defined in the updated breakpoints. Visual and spectrophotometric (fungal growth reduction of >95% compared to the control, read at 540 nm) MICs were compared. Essential (±1 2-fold dilution) and categorical agreements were calculated. Overall, high essential (97.1%) and categorical (99.6%) agreements were found. We obtained 100% categorical agreements for amphotericin B, itraconazole, and posaconazole, and consequently, no errors were found. Categorical agreements were 98.7 and 99.3% for voriconazole and isavuconazole, respectively. Most of the misclassifications for voriconazole and isavuconazole were found to be associated with MIC results falling either in the area of technical uncertainty or within one 2-fold dilution above the breakpoint. The resistance rate was slightly lower when the MICs were obtained by spectrophotometric readings. However, all relevant mutants were correctly classified as resistant. Spectrophotometric determination of azole and amphotericin B MICs against isolates may be a convenient alternative to visual endpoint readings.
Topics: Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Itraconazole; Microbial Sensitivity Tests; Voriconazole
PubMed: 33020164
DOI: 10.1128/AAC.01693-20 -
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 -
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 -
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 -
Biochemistry Apr 2024A major challenge currently facing medicinal chemists is designing agents that can selectively destroy drug resistant fungi and bacteria that have begun to emerge. One... (Review)
Review
A major challenge currently facing medicinal chemists is designing agents that can selectively destroy drug resistant fungi and bacteria that have begun to emerge. One factor that has been overlooked by virtually all drug discovery/development approaches is the supramolecular factor, in which aggregated forms of a drug candidate exhibit low selectivity in destroying targeted cells while the corresponding monomers exhibit high selectivity. This Perspective discusses how we were led to the supramolecular factor through fundamental studies with simple model systems, how we reasoned that the selectivity of monomers of the antifungal agent amphotericin B should be much greater than the selectivity of the corresponding aggregates, and how we confirmed this hypothesis using derivatives of amphotericin B. In a broader context, these findings provide a strong rationale for considering the supramolecular factor in the design of new drug candidates and the testing of virtually all of them.
Topics: Amphotericin B; Antifungal Agents; Fungi; Drug Design; Drug Discovery
PubMed: 38545902
DOI: 10.1021/acs.biochem.3c00721 -
Journal of Infection and Public Health 2018Crytococcus neoformans is an encapsulated yeast that frequently affects immune-compromised patients, although increasingly being detected in the immune-competent host as...
Crytococcus neoformans is an encapsulated yeast that frequently affects immune-compromised patients, although increasingly being detected in the immune-competent host as well. We report a case of disseminated cryptococcosis in a young child in whom no immune deficiency was yet identified. A 4-year-old child presented with high-grade fever, intermittent abdominal pain and generalized skin eruptions for the past two months. He had pallor, firm lymphadenopathy, skin lesions with scarring and firm hepatosplenomegaly. Magnetic resonance imaging of brain and bone-marrow aspiration were normal. Fine-needle-aspiration-cytology of cervical lymph nodes demonstrated Cryptococcus. Serum latex-agglutination test showed a positive titer (1:256). Cryptococcus culture was sterile. The patient received intravenous liposomal amphotericin-B and oral flucytosine for 8 weeks followed by oral fluconazole. Disseminated cryptococcosis with involvement of reticuloendothelial and dermatological systems is rare. Early diagnosis and timely management of associated complications would be life saving.
Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Brain; Child, Preschool; Cryptococcosis; Cryptococcus neoformans; Humans; Immunocompetence; Lymph Nodes; Lymphadenopathy; Magnetic Resonance Imaging; Male; Skin
PubMed: 28965793
DOI: 10.1016/j.jiph.2017.09.015 -
Emerging Microbes & Infections Dec 2024has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive...
has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB's activity against LNP also potentiates the antifungal activity of AmB against other medically important species of and Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome ). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome inhibitor for combating drug-resistant infections.
Topics: Animals; Mice; Amphotericin B; Antifungal Agents; Candida auris; Lansoprazole; Respiration; Cytochromes; Candidiasis
PubMed: 38431850
DOI: 10.1080/22221751.2024.2322649