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Microbiology Spectrum Jun 2022Aspergillus species are a major cause of life-threatening invasive infections and noninvasive diseases. This study seeks to investigate the frequency of Aspergillus...
Aspergillus species are a major cause of life-threatening invasive infections and noninvasive diseases. This study seeks to investigate the frequency of Aspergillus species among Iranian patients and their susceptibility to seven antifungals. In a cross-sectional study, 233 Aspergillus isolates were collected from 11 university hospitals in Iran between 2018 and 2021. Aspergillus isolates were identified based on colony morphology, microscopic characteristics, PCR-restriction fragment length polymorphism (RFLP), and sequencing of the beta-tubulin gene. The CLSI M38-A2 reference methodology was used for antifungal susceptibility testing of amphotericin B, voriconazole, posaconazole, itraconazole, luliconazole, isavuconazole, and caspofungin. Members of Aspergillus section (117/233, 50.2%), Aspergillus section (77/233, 33.1%), Aspergillus section (21/233, 9%), Aspergillus section (14/233, 6%), Aspergillus pseudodeflectus (2/233, 0.85%), and Aspergillus melleus (2/233, 0.85%) were isolated from the samples. The lowest 0.25 MIC values for all isolates tested were for luliconazole (0.016 μg/mL) and isavuconazole (0.250 μg/mL), and the highest value was observed for itraconazole (≥ 8μg/mL). The 90% minimum effective concentration (MEC) value for caspofungin was 0.125 μg/mL. MIC values for voriconazole, amphotericin B, and posaconazole were 1, 2, and 2 μg/mL, respectively. The non-wild-type species were presented for amphotericin B (3%), voriconazole (1.3%), posaconazole (2.6%), luliconazole (1.3%), isavuconazole (1.7%), and caspofungin (4.7%). Positive correlations in the MIC values of azole antifungals were observed, and using one azole increases the MIC value rates of other ones. None of the species were pan-azole resistant. Species of Aspergillus section were the most common Aspergillus species isolated from Iranian samples. Luliconazole, caspofungin, and isavuconazole present the most effective antifungal agents for treatment of infection due to Aspergillus species. Susceptibility tests should be performed frequently in each region for the best management of patients. Aspergillus species are the leading cause of invasive aspergillosis in immunocompromised hosts. The susceptibility of Aspergillus species to antifungal agents might be different. Azole-resistant species have emerged worldwide. Performing susceptibility testing in each region can help in the best management of patients. Here, we show the epidemiology and distribution of Aspergillus species in Iran and their susceptibility patterns for seven antifungal agents. The significant points of the present study are that species of Aspergillus section are the most prevalent Aspergillus species isolated from 11 university hospitals. Luliconazole, caspofungin, and isavuconazole were effective antifungal agents against all Aspergillus species.
Topics: Amphotericin B; Antifungal Agents; Aspergillus; Azoles; Caspofungin; Cross-Sectional Studies; Hospitals, University; Humans; Iran; Itraconazole; Microbial Sensitivity Tests; Voriconazole
PubMed: 35579442
DOI: 10.1128/spectrum.02539-21 -
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 -
Biomedicine & Pharmacotherapy =... Aug 2019This study aimed to evaluate the efficacy of glucantime and amphotericin B (AmB) encapsulated in niosome against cutaneous leishmaniasis (CL) using in vitro and in vivo...
This study aimed to evaluate the efficacy of glucantime and amphotericin B (AmB) encapsulated in niosome against cutaneous leishmaniasis (CL) using in vitro and in vivo models. The niosomal formulations of the drugs alone and in combination were prepared and characterized. Subsequent to the examination of their cytotoxicity, their efficacy was evaluated using an in vitro MTT assay, macrophage model, flow cytometry, and gene expression profiling. For evaluation of therapeutic effect of niosomal combination on the lesion induced by Leishmania major in inbred BALB/c mice, the size of lesions and number of parasites in spleen was assessed. The niosomal formulations demonstrated significantly greater inhibitory effects compared with the non-niosomal forms when the IC was considered. The niosomal combination showed an increase in the apoptotic values and gene expression levels of IL-12 and metacaspase and a decrease in the levels of IL-10 with a dose-response effect. The niosomal combination was also effective in reducing the lesion size and splenic parasite burden in mice. Our findings indicated that there is a synergistic effect between AmB and glucantime in niosomal form in the inhibition of intracellular and extracellular forms of L. tropica. Additionally, the in vivo results on L. major suggest that topical niosomal formulation could be useful in the treatment of CL.
Topics: Amphotericin B; Animals; Antiprotozoal Agents; Apoptosis; Cell Line; Drug Therapy, Combination; Gene Expression Regulation; Inhibitory Concentration 50; Leishmania major; Liposomes; Macrophages; Meglumine Antimoniate; Mice, Inbred BALB C; Parasites; Spleen
PubMed: 31152929
DOI: 10.1016/j.biopha.2019.108942 -
International Journal of Pharmaceutics Dec 2019The current study sought to formulate, optimize, and stabilize amphotericin B (AmB) loaded PEGylated nanostructured lipid carriers (NLC) and to study its ocular...
The current study sought to formulate, optimize, and stabilize amphotericin B (AmB) loaded PEGylated nanostructured lipid carriers (NLC) and to study its ocular biodistribution following topical instillation. AmB loaded PEGylated NLC (AmB-PEG-NLC) were fabricated by hot-melt emulsification followed by high-pressure homogenization (HPH) technique. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-2K-DSPE) was used for surface PEGylation. mPEG-DSPE with different PEG molecular weight, 1 K, 2 K, 5 K, 10 K, and 20 K, were screened for formulation stability. Furthermore, the AmB loaded PEGylated (2K) NLC (AmB-PEG2K-NLC) was optimized using Box-Behnken design with respect to the amount of AmB, castor oil, mPEG-2K-DSPE, and number of high-pressure homogenization cycles as the factors; particle size, zeta potential, PDI, entrapment efficiency, and loading efficiency as responses. Stability of the optimized AmB-PEG2K-NLC was assessed over 4 weeks, at 4 °C as well as 25 °C and effect of autoclaving was also evaluated. AmB-PEG2K-NLC were tested for their in vitro antifungal activity against Candida albicans (ATCC 90028), AmB resistant Candida albicans (ATCC 200955) and Aspergillus fumigatus (ATCC 204305). Cytotoxicity of AmB-PEG2K-NLC was studied in human retinal pigmented epithelium cells. In vivo ocular biodistribution of AmB was evaluated in rabbits, following topical application of PEGylated NLCs or marketed AmB preparations. PEGylation with mPEG-2K-DSPE prevented leaching of AmB and increased the drug load significantly. The optimized formulation was prepared with a particle size of 218 ± 5 nm; 0.3 ± 0.02 PDI, 4.6 ± 0.1% w/w drug loading, and 92.7 ± 2.5% w/w entrapment efficiency. The optimized colloidal dispersions were stable for over a month, at both 4 °C and 25 °C. AmB-PEG2K-NLCs showed significantly (p < 0.05) better antifungal activity in both wild-type and AmB resistant Candida strains and, was comparable to, or better than, commercially available parenteral AmB formulations like Fungizone™ and AmBisome®. AmB-PEG2K-NLC did not show any toxicity up to a highest concentration of 1% (v/v) (percent formulation in medium). Following topical instillation, AmB was detected in all the ocular tissues tested and statistically significant (p > 0.05) difference was not observed between the formulations tested. An optimized autoclavable and effective AmB-PEG2K-NLC ophthalmic formulation with at least one-month stability, in the reconstituted state, has been developed.
Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Cell Line; Chemistry, Pharmaceutical; Drug Carriers; Drug Delivery Systems; Excipients; Humans; Lipids; Male; Nanoparticles; Nanostructures; Particle Size; Polyethylene Glycols; Rabbits; Tissue Distribution
PubMed: 31669555
DOI: 10.1016/j.ijpharm.2019.118771 -
Brazilian Journal of Cardiovascular... Oct 2020Although it is the most common agent among the fungal causes of endocarditis, Candida albicans endocarditis is rare.
INTRODUCTION
Although it is the most common agent among the fungal causes of endocarditis, Candida albicans endocarditis is rare.
OBJECTIVE
To evaluate the efficacy of amphotericin B in the treatment of C. albicans endocarditis beyond a systematic review.
DATA SEARCH
Articles in English, Spanish and Portuguese, conducted in the following databases: MEDLINE, LILACS, IBECS and SciELO, in humans and published in the last 25 years.
STUDY SELECTION
Observational studies, clinical trials, and case series providing data on the amphotericin B use in patients with a C. albicans endocarditis diagnosis without age limitations.
DATA SYNTHESIS
From the initial search (n=79), 25 articles were fully evaluated, of which 19 were excluded for meeting one or more exclusion criteria, remaining five articles (two observational studies and three case series). Patients using amphotericin B demonstrated improvement in survival rates, and its main use was in association with the surgical method as well as with caspofungin association.
CONCLUSION
Literature lacks evidence to conclude about efficacy and safety of amphotericin B in the treatment of fungal endocarditis. Randomized clinical trials are necessary to provide better evidence on the subject.
Topics: Amphotericin B; Antifungal Agents; Candida albicans; Child; Cross-Sectional Studies; Endocarditis; Humans; Infant, Newborn
PubMed: 33118745
DOI: 10.21470/1678-9741-2019-0159 -
Molecules (Basel, Switzerland) Sep 2020The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite , requires continuous innovation at the therapeutic and vaccination levels.... (Review)
Review
The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite , requires continuous innovation at the therapeutic and vaccination levels. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This review presents recent progress in chitosan research for antileishmanial applications. First data on the mechanism of action of chitosan revealed an optimal in vitro intrinsic activity at acidic pH, high-molecular-weight chitosan being the most efficient form, with an uptake by pinocytosis and an accumulation in the parasitophorous vacuole of -infected macrophages. In addition, the immunomodulatory effect of chitosan is an added value both for the treatment of leishmaniasis and the development of innovative vaccines. The advances in chitosan chemistry allows pharmacomodulation on amine groups opening various opportunities for new polymers of different size, and physico-chemical properties adapted to the chosen routes of administration. Different formulations have been studied in experimental leishmaniasis models to cure visceral and cutaneous leishmaniasis, and chitosan can act as a booster through drug combinations with classical drugs, such as amphotericin B. The various architectural possibilities given by chitosan chemistry and pharmaceutical technology pave the way for promising further developments.
Topics: Amphotericin B; Animals; Antimony; Antiprotozoal Agents; Biocompatible Materials; Chitosan; Curcumin; Drug Carriers; Drug Compounding; Humans; Hydrogen-Ion Concentration; Leishmaniasis; Leishmaniasis Vaccines; Macrophages; Nanoparticles; Paromomycin; Pentacyclic Triterpenes; Polymers; Rifampin; Selenium; Thiomalates; Titanium; Triterpenes; Betulinic Acid; Ursolic Acid
PubMed: 32916994
DOI: 10.3390/molecules25184123 -
Parasites & Vectors Dec 2021Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine...
BACKGROUND
Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate.
METHODS
In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated.
RESULTS
The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased.
CONCLUSION
The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated.
Topics: Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Drug Resistance; Female; Leishmania infantum; Leishmaniasis, Visceral; Meglumine Antimoniate; Phosphorylcholine
PubMed: 34886876
DOI: 10.1186/s13071-021-05100-x -
The Cochrane Database of Systematic... Apr 2020Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear.
OBJECTIVES
We assessed evidence in three areas of equipoise. 1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals. 2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy. 3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020.
SELECTION CRITERIA
We evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single-arm trials, prospective cohort studies, and single-arm cohort studies.
DATA COLLECTION AND ANALYSIS
Two review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS-I tool to assess risk of bias in non-randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI).
MAIN RESULTS
We identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis. 1. Induction We found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low-certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high-certainty evidence). We found very low-certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy. 2. Maintenance We found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy. For both induction and maintenance, fluconazole performed poorly in comparison to other azoles. 3. ART We found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died.
AUTHORS' CONCLUSIONS
Liposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions.
Topics: Amphotericin B; Anti-HIV Agents; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Drug Administration Schedule; Fluconazole; HIV Infections; Histoplasmosis; Humans; Induction Chemotherapy; Itraconazole; Kidney; Liposomes; Maintenance Chemotherapy; Randomized Controlled Trials as Topic
PubMed: 32343003
DOI: 10.1002/14651858.CD013594 -
Drug Delivery Dec 2023Most of the drugs are hydrophobic and have low water solubility, therefore posing issues in their absorption and bioavailability. Nonionic surfactants improve the...
Most of the drugs are hydrophobic and have low water solubility, therefore posing issues in their absorption and bioavailability. Nonionic surfactants improve the solubility of hydrophobic drugs by entrapping them in their lipid bilayers. Two nonionic surfactants NODNH-16 and NODNH-18 are synthesized and characterized using different techniques i.e. EI-MS, H NMR, and FTIR. These newly synthesized surfactants were screened for blood hemolysis assay and cell toxicity studies using the NIH/3T3 cell line to assess their biocompatibility. Then amphotericin B was loaded into niosomal vesicles, and the drug entrapment efficiency of these surfactants was measured using UV-visible spectroscopy. The morphology of drug-loaded niosomes of synthesized surfactants was investigated using AFM, and their size, polydispersity, and zeta potential were measured with the Zetasizer instrument. Finally, a simulation study was performed to determine the pattern of self-assembly of the synthesized amphiphiles. Both synthesized nonionic surfactants showed good entrapment efficiency of 60.65 ± 2.12% and 68.45 ± 2.12%, respectively. It was also confirmed that both these synthesized nonionic surfactants were safe and biocompatible and showed less blood hemolysis (i.e. 21.13 ± 2.11% and 23.32 ± 2.45%) and higher 3T3 cells' viability at 150 µg/mL concentration as compared to Tween®-80. The antifungal potential of amphotericin B-loaded niosomes has been evaluated against unicellular multi-fungal species, which showed a promising potential for fungicidal activity. These results are substantiated by constructing a safe vehicle system for drug delivery.
Topics: Mice; Animals; Liposomes; Amphotericin B; Hemolysis; Surface-Active Agents; Hydrazines
PubMed: 36785530
DOI: 10.1080/10717544.2023.2174205 -
Microbiology Spectrum Dec 2022In recent decades, the incidence of infections has increased in immunocompromised patients. This multicenter study aimed to evaluate antifungal activities of 8...
In recent decades, the incidence of infections has increased in immunocompromised patients. This multicenter study aimed to evaluate antifungal activities of 8 antifungal agents against the species isolated from 10 university hospitals in Iran. During the period from Dec 2019 to Dec 2021, species were collected from clinical samples of patients. The isolates were identified by PCR restriction fragment length polymorphism and sequencing methods. The antifungal susceptibility tests of each isolate to eight antifungal agents were performed according to the microdilution CLSI M27, M59, and M60 standard methods. A total of 598 strains were isolated from clinical samples. The most commonly isolated species was C. albicans, followed by C. glabrata, C. parapsilosis, Debaryomyces hansenii (Candida famata), C. tropicalis, (Candida krusei), C. orthopsilosis, Meyerozyma guilliermondii (Candida guilliermondii), Kluyveromyces marxianus (Candida kefyr), and Clavispora lusitaniae (Candida lusitaniae). MIC values in all species were as follows: 0.25 μg/mL for caspofungin and voriconazole; 0.5 μg/mL for amphotericin B and isavuconazole; 2 μg/mL for itraconazole, luliconazole, and posaconazole; and 16 μg/mL for fluconazole. Although 30/285 C. albicans, 15/31 3/12 , 67/125 C. glabrata, 5/15 , 6/60 C. parapsilosis, and 5/23 C. tropicalis isolates were multiazole resistant with resistance to 2 to 4 azoles, pan-azole resistance was not observed. According to our data, Candida albicans and C. glabrata were the most frequent species isolated from clinical samples in Iran. Caspofungin and voriconazole, with lower MIC values, are the most effective than other antifungal agents for the treatment of infections in this region. species cause severe invasive infections of the heart, brain, eyes, bones, and other parts of the body. Knowledge of regional distributions of causative agents and their antifungal susceptibility patterns can help to monitor resistance to antifungal agents of various species and support local and national surveillance programs. In the present study, C. albicans and C. glabrata were the most frequently isolated species from clinical samples in Iran. Increasing rates of non- isolates from the Iranian population should be looked at as alarming due to various levels of intrinsic MIC values or resistance to various antifungal drugs. Caspofungin and voriconazole are recommended over fluconazole for the treatment of infections in the study region. However, amphotericin B and isavuconazole are also active against the most common species isolated from patients. Pan azole-resistant species were not observed in the present study.
Topics: Humans; Amphotericin B; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candidiasis; Caspofungin; Drug Resistance, Fungal; Fluconazole; Iran; Microbial Sensitivity Tests; Tertiary Care Centers; Voriconazole
PubMed: 36445122
DOI: 10.1128/spectrum.02453-22