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British Journal of Clinical Pharmacology May 2018Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children.... (Comparative Study)
Comparative Study
AIMS
Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children.
METHODS
Children admitted to the Royal Children's Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin-related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity.
RESULTS
Seventy-six children received c-amB and 39 received l-amB. Standard drug administration (recommended dose and infusion time) occurred in 74% (56/76) of patients on c-amB and 85% (33/39) on l-amB. In these 89 children, infusion-related reactions were similar for both c-amB and l-amB (23% (13/56) vs. 9% (3/33); P = 0.15); none occurred in children aged <90 days. There was no difference in amphotericin-associated glomerulotoxicity (c-amB 14% (8/56) vs. l-amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c-amB 3.1 vs. l-amB 2.3 mmol kg d ; P = 0.29). Hepatotoxicity occurred more frequently with l-amB than c-amB (83% (24/29) vs. 56% (20/36); P = 0.032).
CONCLUSIONS
When appropriately administered, l-amB was associated with more hepatotoxicity than c-amB, with no difference in infusion-related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.
Topics: Adolescent; Amphotericin B; Antifungal Agents; Australia; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Retrospective Studies; Young Adult
PubMed: 29352486
DOI: 10.1111/bcp.13521 -
Viruses Sep 2022Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the...
Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus-host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by spp. Mosquitoes, although other mechanisms such as blood transfusion, sexual and maternal-fetal transmission have been demonstrated. Symptoms are generally mild, such as fever, rash, joint pain and conjunctivitis, but neurological complications, including Guillain-Barré syndrome, have been associated to this viral infection. During pregnancy, it can cause microcephaly and other congenital abnormalities in the fetus, as well as pregnancy complications, representing a serious health threat. In this study, we show for the first time that Zika virus employs cell membrane lipid rafts as a portal of entry into Vero cells. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) hampers a microbe-host cell interaction through the disruption of lipid raft architecture. Here, we found that Amphotericin B by the same mechanism of action inhibits both Zika virus cell entry and replication. These data encourage further studies on the off-label use of Amphotericin B in Zika virus infections as a new and alternate antiviral therapy.
Topics: Amphotericin B; Animals; Antifungal Agents; Antiviral Agents; Chlorocebus aethiops; Female; Flavivirus; Humans; Membrane Lipids; Membrane Microdomains; Pregnancy; Vero Cells; Zika Virus; Zika Virus Infection
PubMed: 36146865
DOI: 10.3390/v14092059 -
International Journal For Parasitology.... Dec 2019The development of an effective amphotericin B (AmB) topical formulation to replace the systemically toxic injections currently used in cutaneous leishmaniasis (CL)...
The development of an effective amphotericin B (AmB) topical formulation to replace the systemically toxic injections currently used in cutaneous leishmaniasis (CL) treatment is challenging due to poor absorption through the skin. Aiming at an effective local chemotherapy, we designed PLGA (poly(lactide-co-glycolide acid) microparticles loaded with deoxycholate amphotericin B (d-AmB) for both macrophage intracellular targeting and sustained extracellular release. For that, d-AmB/PLGA microparticles with sizes ranging from 0.5 μm to 20 μm were synthesized and tested both in vitro and in vivo. In vitro, d-AmB/PLGA was more selectively active against intracellular amastigotes of Leishmania amazonensis than free d-AmB (selectivity index = 50 and 25, respectively). In vivo, the efficacy of a single intralesional (i.l) injection with d-AmB/PLGA was determined in early and established BALB/c mouse ear lesions. In early lesions, a single injection given on day 10 of infection was more effective in controlling parasite growth than eight i.l. injections with free d-AmB, as measured on day 120. Such d-AmB/PLGA injection was also effective in established lesions (day 30), leading to 97% parasite burden reduction, as compared with d-AmB or liposomal AmB (Ambisome®) i.l. injection containing the same AmB dose. Pharmacokinetic studies showed that following d-AmB/PLGA injection, AmB leaked slower from non-infected than infected ears, yet remaining in the ear tissue for as long as 30 days. Of interest, AmB was not detectable in the circulating plasma for at least two weeks of d-AmB/PLGA injection, contrasting with the rapid and durable (2 days) detection after free d-AmB injection. Despite the transient ear swelling and local cell infiltration, no alterations in AST, ALT and creatinine serum levels was induced by d-AmB/PLGA. For its approved components, local efficacy, and single-dose applicability, this novel and safe AmB microparticle depot formulation has strong potential as a new therapy for human CL.
Topics: Amphotericin B; Animals; Antiprotozoal Agents; Deoxycholic Acid; Drug Combinations; Drug Delivery Systems; Ear; Leishmaniasis, Cutaneous; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Polyglactin 910
PubMed: 31331828
DOI: 10.1016/j.ijpddr.2019.06.001 -
Journal of Clinical Microbiology Aug 2021The global incidence of mucormycosis has increased in recent years owing to higher numbers of individuals at risk for these infections. The diagnosis and treatment of...
The global incidence of mucormycosis has increased in recent years owing to higher numbers of individuals at risk for these infections. The diagnosis and treatment of this aggressive fungal infection are of clinical concern due to differences in species distribution in different geographic areas and susceptibility profiles between different species that are capable of causing highly aggressive infections. The purpose of this study was to evaluate the epidemiology and susceptibility profiles of Mucorales isolates in the United States over a 52-month period. Species identification was performed by combined phenotypic characteristics and DNA sequence analysis, and antifungal susceptibility testing was performed by CLSI M38 broth microdilution for amphotericin B, isavuconazole, itraconazole, and posaconazole. During this time frame, 854 isolates were included, representing 11 different genera and over 26 species, of which (58.6%) was the predominant genus, followed by (19.6%). The majority of isolates were cultured from the upper and lower respiratory tracts (55%). Amphotericin B demonstrated the most potent activity, with geometric mean (GM) MICs of ≤0.25 μg/ml against all genera with the exception of species (GM MIC of 1.30 μg/ml). In head-to-head comparisons, the most active azole was posaconazole, followed by isavuconazole. Differences in azole and amphotericin B susceptibility patterns were observed between the genera with the greatest variability observed with isavuconazole. Awareness of the epidemiology of Mucorales isolates and differences in antifungal susceptibility patterns in the United States may aide clinicians in choosing antifungal treatment regimens. Further studies are warranted to correlate these findings with clinical outcomes.
Topics: Amphotericin B; Antifungal Agents; Fungi; Humans; Itraconazole; Microbial Sensitivity Tests; Mucorales; Mucormycosis; United States
PubMed: 34232068
DOI: 10.1128/JCM.01230-21 -
Scientific Reports Dec 2022In the present work, single wall carbon nanotubes (SWCNT) were successively functionalized with phospholipid DSPE-PEG carboxylic acid, and then, with ethylenediamine...
In the present work, single wall carbon nanotubes (SWCNT) were successively functionalized with phospholipid DSPE-PEG carboxylic acid, and then, with ethylenediamine (EDA), to obtain double functionalized single wall carbon nanotube (DFSWCNT). Then, DFSWCNT was applied as a carrier for delivering amphotericin B (Amb) and EGFP plasmid. FSWCNT's concentration obtained via UV-visible analysis was 0.99 mg/mL. The TGA analysis results provided the lost weights of DSPE-PEG-COOH, EDA, Amb and SWCNT impurities. XPS results showed that carbon atoms' percentage decreased during the functionalization processes from 97.2% (SWCNT) to 76.4% (FSWCNT) and 69.9% (DFSWNCT). Additionally, the oxygen atoms' percentage increased from 2.3% (SWCNT) to 21% and 22.5% for FSWCNT and DFSWCNT, respectively. New bonds such as C-N and N-C=O appeared in the synthesized nanocarrier. The I/I ratio in Raman analysis decreased from 7.15 (SWCNT) to 4.08 (FSWCNT). The amount of Amb released to phosphate buffer saline medium was about 33% at pH = 5.5 and 75% at pH = 7.4 after 48 h. CCK8 results confirmed that the toxicity of functionalized SWCNT had decreased. In a 2:1 ratio of DFSWCNT/EGFP plasmid, the cell viability (87%) and live transfected cells (56%) were at their maximum values. The results indicate that carbon nanotubes have the potential to be applied as drug/gene delivery systems with outstanding properties such as high loading capacity and easy penetration to cell membrane.
Topics: Nanotubes, Carbon; Amphotericin B
PubMed: 36476955
DOI: 10.1038/s41598-022-25222-1 -
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 -
Drug Delivery Nov 2017Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation... (Comparative Study)
Comparative Study
Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p < 0.05) improved the bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.
Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Biological Availability; Biomarkers; Blood Urea Nitrogen; Candida albicans; Creatinine; Drug Carriers; Drug Compounding; Glycyrrhizic Acid; Hemolysis; Kidney Diseases; Lactic Acid; Microbial Sensitivity Tests; Nanoparticles; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Technology, Pharmaceutical
PubMed: 28155565
DOI: 10.1080/10717544.2016.1228715 -
BMC Oral Health Apr 2023Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral... (Observational Study)
Observational Study
BACKGROUND
Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non-Candida albicans species in mixed oral infections with Candida albicans. Non-C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity.
METHODS
An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014-2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied.
RESULTS
Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2-3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non-C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin.
CONCLUSION
C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer.
TRAIL REGISTRATION
The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.
Topics: Humans; Candidiasis, Oral; Fluconazole; Amphotericin B; Anidulafungin; Microbial Sensitivity Tests; Antifungal Agents; Candida; Candida albicans; Neoplasms; Drug Resistance, Fungal
PubMed: 37072843
DOI: 10.1186/s12903-023-02950-y -
Antimicrobial Agents and Chemotherapy Jun 2018Our studies showed that a combination of amphotericin B and terbinafine had synergistic effects against the majority of melanized fungi associated with...
Our studies showed that a combination of amphotericin B and terbinafine had synergistic effects against the majority of melanized fungi associated with chromoblastomycosis (CBM) and similar infections, including those with , , , , , , , and This drug combination could provide an option for the treatment of severe or unresponsive cases of CBM, particularly in cases due to species of and .
Topics: Amphotericin B; Antifungal Agents; Ascomycota; Chromoblastomycosis; Exophiala; Microbial Sensitivity Tests; Phialophora; Terbinafine
PubMed: 29581111
DOI: 10.1128/AAC.00270-18 -
Antimicrobial Agents and Chemotherapy Jun 2022Inhaled formulations of amphotericin B are the most widely used antifungal prophylactic agents in lung transplant recipients, yet there are limited data on their safety....
Inhaled formulations of amphotericin B are the most widely used antifungal prophylactic agents in lung transplant recipients, yet there are limited data on their safety. We performed a single-center retrospective cohort study of 603 consecutive patients who underwent lung transplantation between 2012 and 2017 and received antifungal prophylaxis with inhaled amphotericin B lipid complex (iABLC) from the day of transplantation until hospital discharge. Of 603 patients, 600 (99.5%) received ≥1 dose of iABLC, and 544 (90.2%) completed the recommended prophylactic course. In total, 4,128 iABLC doses (median, 5; range, 1 to 48 per patient) were administered; 24 patients received >3 months of therapy. Only one (0.2%) patient discontinued therapy due to a drug-attributable adverse event. During the first posttransplant year, 80 (13.3%) patients died (median time to death, 171 days; interquartile range [IQR], 80 to 272 days), and 3,352 (median, 6 per patient) lung biopsies were performed; 414 (68.7%) patients developed biopsy-proven acute cellular rejection. One-year adverse events in our cohort of lung transplant recipients treated with iABLC during transplant hospitalization matched national outcomes for rejection, graft loss, and death. iABLC is a safe and well-tolerated antifungal prophylactic agent in lung transplant recipients.
Topics: Amphotericin B; Antifungal Agents; Humans; Lung; Lung Transplantation; Mycoses; Retrospective Studies; Transplant Recipients
PubMed: 35506698
DOI: 10.1128/aac.00283-22