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Histoplasmosis is a respiratory disease caused by Histoplasma capsulatum, a dimorphic fungus, with high mortality and morbidity rates, especially in immunocompromised patients. Considering the small existing therapeutic arsenal, new treatment approaches are still required. Chitosan, a linear polysaccharide obtained from partial chitin deacetylation, has anti-inflammatory, antimicrobial, biocompatibility, biodegradability, and non-toxicity properties. Chitosan with different deacetylation degrees and molecular weights has been explored as a potential agent against fungal pathogens. In this study, the chitosan antifungal activity against H. capsulatum was evaluated using the broth microdilution assay, obtaining minimum inhibitory concentrations (MIC) ranging from 32 to 128 µg/mL in the filamentous phase and 8 to 64 µg/mL in the yeast phase. Chitosan combined with classical antifungal drugs showed a synergic effect, reducing chitosan's MICs by 32 times, demonstrating that there were no antagonistic interactions relating to any of the strains tested. A synergism between chitosan and amphotericin B or itraconazole was detected in the yeast-like form for all strains tested. For H. capsulatum biofilms, chitosan reduced biomass and metabolic activity by about 40% at 512 µg/mL. In conclusion, studying chitosan as a therapeutic strategy against Histoplasma capsulatum is promising, mainly considering its numerous possible applications, including its combination with other compounds. [ABSTRACT FROM AUTHOR]

Background The EnACT trial was a phase 2 randomized clinical trial conducted in Uganda, which evaluated a novel orally delivered lipid nanocrystal (LNC) amphotericin B in combination with flucytosine for the treatment of cryptococcal meningitis. When flucytosine (5FC) is used as monotherapy in cryptococcosis, 5FC can induce resistant Cryptococcus mutants. Oral amphotericin B uses a novel drug delivery mechanism, and we assessed whether resistance to 5FC develops during oral LNC–amphotericin B therapy. Methods We enrolled Ugandans with HIV diagnosed with cryptococcal meningitis and who were randomized to receive 5FC and either standard intravenous (IV) amphotericin B or oral LNC–amphotericin B. We used broth microdilution to measure the minimum inhibitory concentration (MIC) of the first and last cryptococcal isolates in each participant. Breakpoints are inferred from 5FC in Candida albicans. We measured cerebral spinal fluid (CSF) 5FC concentrations by liquid chromatography and tandem mass spectrometry. Results Cryptococcus 5FC MIC50 was 4 µg/mL, and MIC90 was 8 µg/mL. After 2 weeks of therapy, there was no evidence of 5FC resistance developing, defined as a >4-fold change in susceptibility in any Cryptococcus isolate tested. The median CSF 5FC concentration to MIC ratio (interquartile range) was 3.0 (1.7–5.5) µg/mL. There was no association between 5FC/MIC ratio and early fungicidal activity of the quantitative rate of CSF yeast clearance (R 2 = 0.004; P =.63). Conclusions There is no evidence of baseline resistance to 5FC or incident resistance during combination therapy with oral or IV amphotericin B in Uganda. Oral amphotericin B can safely be used in combination with 5FC. [ABSTRACT FROM AUTHOR]

Candida albicans and non-albicans Candida species are a common cause of human mucosal infections, as well as bloodstream infections and deep mycoses. The emergence of resistance of Candida spp. to antifungal drugs used in practice requires the search for new antimycotics. The present study unravels the antifungal potential of the synthetic dialk(en)ylthiosulfinates in comparison with an enzymatic in situ methionine γ-lyase-based thiosulfinate generation system (TGS). The kinetics of the TGS reaction, namely, the methionine γ-lyase-catalyzed β-elimination of S-alk(en)yl-L-cysteine sulfoxides, was investigated via 1H NMR spectroscopy for the first time, revealing fast conversion rates and the efficient production of anticandidal dialk(en)ylthiosulfinates. The anticandidal potential of this system vs. synthetic thiosulfinates was investigated through an in vitro assay. TGS proved to be more effective (MIC range 0.36–1.1 μg/mL) than individual substances (MIC range 0.69–3.31 μg/mL). The tested preparations had an additive effect with the commercial antimycotics fluconazole, amphotericin B and 5-flucytosine demonstrating a fractional inhibitory coefficient index in the range of 0.5–2 μg/mL. TGS can be regarded as an attractive candidate for the targeted delivery of antimycotic thiosulfinates and for further implementation onto medically implanted devices. [ABSTRACT FROM AUTHOR]

Mucormycosis or grimmer popular name, "black fungus" has evolved public concern in context of covid-19 pandemic, Covid Associated Mucormycosis (CAM) seen in Covid-19 pandemic and as a post covid sequelae. The present study was conducted to find out the incidence of the Mucormycosis, and to study its association with post-covid status and co-morbidities. A retrospective study conducted at tertiary care centre over a period of four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease. 59 patients had CAM, 47 patients had rhino-orbital Mucormycosis, followed by nasal and paranasal Mucormycosis in 8 patients, 3 patients with rhino-orbital-cerebral Mucormycosis, and one patient with pulmonary Mucormycosis. Diabetes mellitus was present in all 59 patients, 60.41% who had HbA1c > 10 (range 7–15), and 39.58% had HbA1c < 10 with range 6–13. Only 8.33% had controlled diabetes status, uncontroled hypertension and diabetes was seen in 34.02%. All patients were started with IV amphotericin B anti-fungal drug, and followed by oral posaconazole. Depending upon the extent of the disease surgical debridement was done in 52 patients. All patients had history of steroid intake. 7 mortality was there. Uncontrolled diabetes, over-zealous use of steroids, uncontrolled underlying primary disease or co-morbidities, prolonged hospitalization in intensive care unit or normal wards, and hyperventilation all these factors together aggravated the CAM. So it's proper management based on, prompt diagnosis, reversal of predisposing condition with proper medical and aggressive surgical debridement remain the corner stone for this deadly CAM. [ABSTRACT FROM AUTHOR]

Plant extracts are used to make herbal remedies with no side effects and little expense. During the COVID-19 pandemic, fungal species responsible for mucormycosis were found resistant to a variety of antifungals, including flucytosine, ketoconazole, fluconazole, voriconazole, itraconazole and echinocandins, due to their variable susceptibility. Amphotericin B is widely used a s an antifungal agent due to its high inhibition capacity against various fungi. The present study aimed to compare the antifun gal potential of Amphotericin B and herbal extract in vitro. The experiment was designed to measure zones of inhibition with the help of well-diffusion method. Four solvents, viz. methanol, chloroform, hexane and distilled water, were used to extract plant extract. The efficiency of plant extracts was found to be low compared to Amphotericin B (1.4mm). Chloroform extract of Boerhavia diffusa was found antifungal against Candida albician and C. tropicalis (0.45mm). Methanol and hexane extract of Eichhornia crassipes showed higher antifungal activity (1.35mm) and (1.75mm), respectively. The plant extracts also showed significant antifungal activity against C. tropicalis, revealing its potential to be used as a natural antifungal agent (1.1mm). Additionally, the findings showed that the chloroform and methanol extracts of B. diffusa and E. crassipes were also efficient against C. albician and C. tropicalis. The findings provide important insights about using plant extracts as a potential alternative to conventional antifungal agents. [ABSTRACT FROM AUTHOR]

Objective Fungal rhinosinusitis is on the rise worldwide and it is endemic especially in North India. The main purpose of this study was to determine the antifungal resistance profile of fungal isolates from the cases of fungal rhinosinusitis. Methods Antifungal susceptibility testing of isolated fungi to fluconazole, amphotericin B, itraconazole, and voriconazole was determined by standard CLSI broth microdilution method. Results Sixty-eight fungal isolates of Aspergillus spp. (n = 49), Rhizopus spp. (n = 9), Candida spp. (n = 4), Penicillium spp. (n = 2), Mucor spp. (n = 2), Bipolaris spp. (n = 1), and Alternaria spp. (n = 1) were obtained from 60 different clinical samples as exudate from nasal mucosa (n = 28), allergic mucin (n = 8), nasal lavage (n = 2), tissue biopsy from nasal polyps (n = 14), and intraoperative nasal mucosa (n = 8). Of the 68 isolates, 75% were resistant to fluconazole, 13.23% were resistant to itraconazole, 2.94% to amphotericin B, and none were resistant to voriconazole. Aspergillus flavus (5%) was the only fungi found resistant to amphotericin B, while against itraconazole, A. flavus (7.5%) and A. niger (100%) were found resistant. All the isolates of A. flavus , A. fumigatus , A. niger , and Penicillium spp. were resistant to fluconazole. Conclusion Although amphotericin B stills remains to be the most effective drug, more prospective studies are needed for the requirement of knowledge of the sensitivity pattern for optimal treatment and reduction in morbidity in the long run. [ABSTRACT FROM AUTHOR]

Leishmania (Mundinia) martiniquensis is a newly described species that causes human visceral, disseminated, and mucocutaneous leishmaniases. Amphotericin B deoxycholate (AmpB) is the first-line drug for the treatment of leishmaniasis in Thailand; however, several relapse cases of leishmaniasis caused by L. martiniquensis have been documented. In this study, in vitro susceptibility to AmpB and miltefosine (MIL) of wild-type (before treatment, LSCM1) and two AmpB-resistant L. martiniquensis strains (an in vitro-induced AmpB-resistant strain, AmpBRP2i, and a relapse strain, LSCM1-6) were determined. Results reveal that the IC50 value and resistance index against both drugs of promastigotes and intracellular amastigotes of the AmpBRP2i and LSCM1-6 strains were statistically significantly higher than those of the LSCM1 strain suggesting that cross-resistance with MIL occurred in both AmpB-resistant strains. The results of this study advocate further investigation into mechanisms that involve the complex nature of AmpB/MIL resistance in L. martiniquensis and development of effective methods for the identification of the AmpB-resistant parasites to help delivery of appropriate treatments for patients and for epidemiological surveys to survey the potential spread of drug-resistant strains. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this systematic review was to analyse the benefits of utilizing posaconazole as a single drug therapy or in combination with other antifungals for the treatment of maxillary mucormycosis  as opposed to sole use of amphotericin B. Materials and methods: Databases (MEDLINE via PubMed, Cochrane, EBSCO-host, Scopus, Science Direct, Clinical Trial Registry- India (CTRI) and Google scholar), review articles were searched from 1997 to 2022, using various MeSH terms. Results: After application of the inclusion and exclusion criteria, four articles were finally selected. Three-month survival rate and duration of hospital stay were analysed as primary outcomes. There was no difference in survival among cases of maxillary mucormycosis treated with either drug alone. Death reported after treatment with combination treatment was less as compared to that with amphotericin B alone; however, there was non-significant difference in survival among cases treated with posaconazole in addition to amphotericin B or amphotericin B alone. Conclusion: Posaconazole can be used a single drug therapy for the treatment of maxillary mucormycosis due to its benefits outweighing its risks. The limitations of this study are the paucity of studies and Randomized Controlled Trials available in the literature in this field of study. [ABSTRACT FROM AUTHOR]

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, 1H 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. [ABSTRACT FROM AUTHOR]

Topical drug delivery is preferable route over systemic delivery in case of Cutaneous leishmaniasis (CL). Among the available agents, amphotericin B (AmB) and pentamidine (PTM) showed promising result against CL. However, monotherapy is associated with incidences of reoccurrence and resistance. Combination therapy is therefore recommended. Thin film hydration method was employed for amphotericin B-pentamidine loaded niosomes (AmB-PTM-NIO) preparation followed by their incorporation into chitosan gel. The optimization of AmB-PTM-NIO was done via Box Behnken Design method and in vitro and ex vivo analysis was performed. The optimized formulation indicated 226 nm particle size (PS) with spherical morphology, 0.173 polydispersity index (PDI), −36 mV zeta potential (ZP) and with entrapment efficiency (EE) of 91% (AmB) and 79% (PTM), respectively. The amphotericin B-pentamidine loaded niosomal gel (AmB-PTM-NIO-Gel) showed desirable characteristics including physicochemical properties, pH (5.1 ± 0.15), viscosity (31870 ± 25 cP), and gel spreadability (280 ± 26.46%). In vitro release of the AmB and PTM from AmB-PTM-NIO and AmB-PTM-NIO-Gel showed more prolonged release behavior as compared to their respective drug solution. Higher skin penetration, greater percentage inhibition and lower IC50 against the promastigotes shows that AmB-PTM-NIO has better antileishmanial activity. The obtained findings suggested that the developed AmB-PTM-NIO-Gel has excellent capability of permeation via skin layers, sustained release profile and augmented anti-leishmanial outcome of the incorporated drugs. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) is regarded as a first-line therapy against life-threatening invasive fungal infections. Due to its poor oral bioavailability, AmB is restricted to intravenous administration in clinical practice. As science continues to move forward, two lipid-based formulations are successfully developed for oral AmB administration, currently undergoing phase I clinical trials. Encouragingly, lipid-AmB conjugates with emulsions also exhibit a better bioavailability, which may be another strategy to design oral AmB formulation in clinical practice. Thus, this review mainly focused on the two lipid-based formulations in clinical trials, and discussed the potential perspectives of AmB-lipid conjugation-loaded nanocochleates and emulsions. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Candida albicans (C. albicans) is recognized as the most common opportunistic pathogen in patients with an impaired immune system, and due to the frequent use of antifungal medicine, a variety of drug-resistant species are developing. Probiotics are a part of the human microbiome and natural competitors of Candida by producing lactic acid, low pH, and other secreted metabolites. The role of probiotics in preventing fungal infections has always been discussed. Purpose: This study aimed to investigate the antifungal effect of Lactobacillus casei (L. casei) on fluconazole- and amphotericin B-resistant C. albicans species isolated from the oral cavity of acute myeloid leukemia patients. Materials and Method: In this experimental study, eight strains of fluconazole- and amphotericin B-resistant C. albicans were used. The antifungal effects of probiotic L. casei and nystatin were measured by the co-aggregation method 1, 2, and 4 h after beginning the study. After each hour of exposure, C. albicans and L. casei colonies were counted. Results: L. casei had a significant ability to aggregate with both fluconazole- and amphotericin B-resistant C. albicans in all designated intervals, which increased with time. In the first hour of the study, no significant difference was observed between the effects of L. casei on the two drug-resistant strains. However, as time passed, it had a more significant antifungal effect on fluconazole, compared to amphotericin B resistant species (p Value<0.001). Cell counts showed that the number of fungal cells decreased significantly as time passed (p< 0.001). Conclusion: L. casei had a significant ability to aggregate with both drug-resistant C. albicans species and showed higher antifungal activity on fluconazole-resistant than amphotericin B-resistant species. [ABSTRACT FROM AUTHOR]

This report highlights the role of local amphotericin B (AMB) injection in cases of maxillary mucormycosis. The COVID-19 pandemic has resulted in a dramatic rise in the number of rhino-orbital mucormycosis cases. Although extensive surgical debridement remains the gold standard treatment, tissue salvage is desirable. The cases of two patients treated with local AMB are reported here, indicating that early intervention for maxillary fungal sinusitis in the form of local AMB may avoid the need for more invasive treatment. [ABSTRACT FROM AUTHOR]

Amphotericin B (AMB) is a polyene macrolide antifungal agent used for treating invasive fungal infections. Liposomal AMB is a lipid dosage form, available as AmBisome, which reduces the toxicity of the drug. A simple HPLC‐UV method was developed for the determination of AMB in plasma to study its pharmacokinetic profile in a critical patient receiving AmBisome and treated with extracorporeal replacement therapies. Sample preparation was performed using plasma deproteinization and drug release from liposome by the addition of acetonitrile (ACN)/zinc sulfate and ultrasonication. Chromatographic separation was performed using a C18 column and a mobile phase consisting of phosphate buffer (pH 3.0)/ACN (65/35, v/v). The UV detector was set at 407 nm. The total run time analysis was 23 min. The method was validated according to the standard guidelines and applied to study the pharmacokinetics of AMB in a critical patient. The total run time analysis obtained was shorter than that of the previously reported methods, being useful for therapeutic drug monitoring or pharmacokinetic profile research. [ABSTRACT FROM AUTHOR]

We report the case of a forest ranger who developed a polymicrobial infection with Mucor circinelloides after traumatic forearm amputation. Based on our case report we discuss epidemiology and management of this rare and potentially fatal infection. [ABSTRACT FROM AUTHOR]

Chromoblastomycosis is a chronic granulomatous mycosis of the skin and subcutaneous tissue caused by traumatic inoculation with dematiaceous fungi. This disease primarily affects agricultural workers, who are mostly men. We present a case of chromoblastomycosis in a 63-year-old male farmer patient with dermatosis over 50 years of evolution, with warty, erythematous, and scaly plaques that predominate on the left hemithorax. Direct examination with potassium hydroxide (KOH) revealed numerous fumagoid cells. Amplification and sequencing of the internal transcribed spacer (ITS) and translation elongation factor 1-alpha (TEF-1a) gene revealed that chromoblastomycosis was caused by Cladosporium cladosporioides. The chromoblastomycosis was treated with itraconazole and fluconazole without any improvement, and amphotericin B was administered with partial improvement. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 62-year-old African American man with a history of sarcoidosis who developed worsening abdominal symptoms. The patient's medical history included sarcoidosis, open-angle glaucoma, and benign prostatic hyperplasia. CT scans revealed enlargement of the liver and spleen, lesions on the adrenal glands, and fibrotic changes in the lungs. A bone marrow biopsy confirmed the presence of noncaseating granulomas consistent with Histoplasma species. The patient was treated with amphotericin B and itraconazole. The article highlights the importance of considering opportunistic infections in patients with sarcoidosis and conducting a thorough evaluation for accurate diagnosis and appropriate treatment. The document is a disclosure form for a study conducted by Manush Sondhi, Anusha Vuppala, and Madiha Tariq, who were responsible for the study's design, data acquisition, analysis, and interpretation. [Extracted from the article]

Invasive fungal infections are a primary reason for high mortality in immunocompromised people, especially in critically ill patients, such as intensive care unit (ICU) patients, advanced cancer patients, or severe burn patients. Hypernatremia also can increase mortality in severely ill patients. Amphotericin B (AmB) is the gold standard for treating infections, but in severely ill patients, AmB can cause hematotoxicity when administered intravenously due to its interaction with cholesterol on red blood cell membranes. This results in limited doses of AmB and affects the treatment of infections. The proportion of cholesterol molecules in membrane lipids in red blood cells is as high as 50 mol%, and the sodium ions can influence the interaction between AmB and lipids on the membrane. Therefore, in the complex clinical situation of a severely ill patient with a fungal infection and hypernatremia, the interaction between amphotericin B and the red blood cell membranes is worth studying in depth. In this work, the interaction between AmB and the dipalmitoyl phosphatidylcholine (DPPC)/cholesterol mixed monolayer in the presence of high sodium ion levels was studied when the proportion of cholesterol was 50%. The results show that the effect of AmB on reducing the monolayer’s area at a high level of sodium ions is slightly stronger at 30 mN/m. The effect of AmB on reducing the elastic modulus of the DPPC/Chol monolayer is significantly weakened by a high sodium ion level, compared with the level of sodium ions at normal physiological concentration. The higher the sodium ion concentration, the weaker the intermolecular force of the DPPC/Chol/AmB mixed monolayers. The scanning electron microscope (SEM) and atomic force microscopy (AFM) observations suggest that at a high sodium ion level, the presence of AmB significantly reduces the surface roughness of the DPPC/Chol monolayer. AmB may bind to cholesterol molecules, and it isolates cholesterol from the monolayer, resulting in a reduced height of the cholesterol-rich monolayer and an increasingly dispersed monolayer region. The results are beneficial to understanding the mechanism of impact of a high sodium ion level on the relationship between AmB and red blood cell membranes rich in cholesterol and are valuable for understanding the hemolytic toxicity of AmB to red blood cells at a high sodium ion level.

Background and Objectives: Amphotericin B is a broad-spectrum antifungal agent commonly used to treat Candida haemulonii infection. C. haemulonii was isolated from patients reported to be intrinsically resistant to amphotericin B, encoded by the ERG2 and ERG11 genes. However, there have been limited studies concerning amphotericin B-resistant C. haemulonii in Indonesia. The objective of this study is to explore the phenotypic and genotypic characteristics (ERG2 and ERG11) of C. haemulonii isolated from the ICU of a referral hospital in Indonesia. Materials and Methods: Identification and susceptibility tests were conducted using VITEK2. Thereafter, DNA was extracted and amplified using conventional PCR followed by DNA sequencing (Sanger method). Results: The results of the phenotypic susceptibility test showed that all C. haemulonii were resistant to amphotericin B. ERG2 and ERG11 sequences showed the same amino acid sequence and corresponded to references that are resistant to amphotericin B. Conclusion: The resistant properties of C. haemulonii against amphotericin B found in this study require further exploration, including comparing resistant and sensitive C. haemulonii to amphotericin B. In addition, it is necessary to analyze other genes besides ERG2 and ERG11.

Background and Objectives: The presence of fungi in the respiratory tract as mycobiome, particularly Candida species (spp.), remains a serious problem due to increasing numbers of immunocompromised pa-tients. The confirmed reliable existence of these pathogens due to frequent colonization is essential. This investigation aimed to recognize Candida spp. among isolates from bron-choalveolar lavage of immunocompromised and critically ill patients and to evaluate their susceptibility to antimycotic drugs. Materials and Methods: Bronchoalveolar lavage fluid was collected from 161 hospitalized patients presenting with suspected respiratory fungal infection /colonization. The specimens were examined by standard molecular and mycological assays. Candida spp. were recognized with sequence assessment of the D1-D2 section of the large subunit ribosomal DNA. The susceptibility of Candida isolates to common antimycotic drugs was distinguished by standard broth micro-dilution. Results: Seventy-one clinical isolates of Candida spp. were recognized. Candida albicans was the most frequent, followed by C. glabrata, C. krusei (Pichia kudriavzevii), C. dubliniensis, C. parapsilosis, and C. tropicalis. We found 5.1% of C. albicans isolates and 8% of C. glabrata isolates to show resistance to fluconazole. The whole of the Candida spp. were sensitive to amphotericin B and caspofungin. Conclusion: This study demonstrated that C. albicans and C. glabrata are the most common isolates of bronchoalveolar lavage fluid in patients, and the drug susceptibility screening confirmed that amphotericin B and caspofungin are effective against Candida spp. but some C. glabrata and C. albicans isolates showed resistance to fluconazole.

Summary: Background: Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to quantify the proportion of relapses observed at and beyond 6-months using the Infectious Diseases Data Observatory (IDDO) systematic review (SR) database. Methods: Studies in the IDDO SR database (1983–2021; 160 studies) were eligible for inclusion if follow-up was at least 6-months, relapse was clearly reported, and patients with HIV coinfections were excluded. Meta-analysis of single proportion was undertaken and the estimates were reported with 95% confidence intervals (CI). Findings: Overall, 131 studies enrolling 27,687 patients were included; 1193 patients relapsed. In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5% [95% CI: 2.6%–7.5%; I2 = 66.2%] following single dose liposomal amphotericin B (L-AmB) and 1.5% [95% CI: 0.7%–3.3%; I2 = 0%] for L-AmB in a combination therapy. In East Africa (EA), corresponding estimates were 3.8% [95% CI: 1.3%–10.9%; I2 = 75.8%] following pentavalent antimony (PA), and 13.0% [95% CI: 4.3%–33.6%; I2 = 0%] for PA + paromomycin. From 21 studies with follow-up longer than 6-months, 0.6% [95% CI: 0.2%–1.8%; I2 = 0%] of patients relapsed after 6-months and estimated 27.6% [95% CI: 11.2%–53.4%; I2 = 12%] of relapses would have been missed by a 6-month follow-up. Interpretation: The estimated relapse proportion ranged from 0.5% to 4.5% in ISC and 3.8%–13.0% in EA with the currently recommended drugs. Over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted. Funding: Wellcome Trust (ref: 208378/Z/17/Z).

A 37-year-old man presented with chronic cavitary pulmonary aspergillosis and hemoptysis refractory to systemic antifungal therapy with voriconazole and bronchial artery embolization. Surgical excision was unfeasible due to the patient's refusal of blood transfusions. Ten sessions of intracavitary instillation of amphotericin B via flexible bronchoscopy were then performed. Hemoptysis cessation and aspergilloma resolution were achieved, with no toxicity or side effects, and the clinical benefits were sustained at six months of follow-up.

AmphL is a cytochrome P450 enzyme that catalyzes the C8 oxidation of 8-deoxyamphotericin B to the polyene macrolide antibiotic, amphotericin B. To understand this substrate selectivity, we solved the crystal structure of AmphL to a resolution of 2.0 Å in complex with amphotericin B and performed molecular dynamics (MD) simulations. A detailed comparison with the closely related P450, PimD, which catalyzes the epoxidation of 4,5-desepoxypimaricin to the macrolide antibiotic, pimaricin, reveals key catalytic structural features responsible for stereo- and regio-selective oxidation. Both P450s have a similar access channel that runs parallel to the active site I helix over the surface of the heme. Molecular dynamics simulations of substrate binding reveal PimD can "pull" substrates further into the P450 access channel owing to additional electrostatic interactions between the protein and the carboxyl group attached to the hemiketal ring of 4,5-desepoxypimaricin. This substrate interaction is absent in AmphL although the additional substrate -OH groups in 8-deoxyamphotericin B help to correctly position the substrate for C8 oxidation. Simulations of the oxy-complex indicates that these -OH groups may also participate in a proton relay network required for O2 activation as has been suggested for two other macrolide P450s, PimD and P450eryF. These findings provide experimentally testable models that can potentially contribute to a new generation of novel macrolide antibiotics with enhanced antifungal and/or antiprotozoal efficacy.

Background and purpose: Zygomycosis (mucormycosis) is a rare fungal infection with high morbidity and mortality. This study evaluated mucormycosis's clinical and paraclinical features in patients admitted to Buali Hospital in Sari & Razi Hospital in Ghaemshahr, Mazandaran Province, Iran. Materials and methods: This retrospective and cross-sectional study reviewed the patients' files with proven or probable mucormycosis admitted to Buali & Razi hospitals from 20 April 2011 to 20 April 2018. The Student's T-test and Fisher's exact test were performed for data analysis using SPSS version 27 software. P ≤ 0.05 was considered as a significant value. Results: Out of 33 patients studied, 18 (54.55%) were female and 15 (45.45%) were male. The average age of the patients was 48.84 years. Among the signs and symptoms of the disease, most cases were related to headache. Diabetes was the most common underlying disease in these patients 28 (93.3%). The mortality rate in these patients was 48.48%, of which 25% related to mucormycosis. The genus Mucor and Rhizopus were the most common agents isolated in 9 cases of positive cultures. Conclusion: Results indicate that people with diabetes are more susceptible to mucormycosis than others, and that control and reduction of diabetes in the community can significantly reduce the incidence of mucormycosis. surgery combined with timely medical treatment also has the highest survival rate.

Katherine Daniel,1 Rachel G Greenberg,2,3 Angelique Boutzoukas,2,3 Lakshmi Katakam4 1Duke University School of Medicine, Durham, NC, USA; 2Department of Pediatrics, Duke University, Durham, NC, USA; 3Duke Clinical Research Institute, Durham, NC, USA; 4Department of Pediatrics, Neonatal-Perinatal Medicine, Durham, NC, USACorrespondence: Lakshmi Katakam, Department of Pediatrics, Neonatal-Perinatal Medicine, 2400 Pratt Street, North Pavilion Building, 8th Floor, Durham, NC, 27705, USA, Tel +1 919 681 6035, Fax +1 919 681 6085, Email lakshmi.katakam@duke.eduAbstract: Invasive candidiasis can cause severe illness in immunocompromised hosts, such as premature infants. Clinical presentation in neonates is variable and often characterized by non-specific signs with potential to involve several organ systems. Awareness of risk factors for Candida infections in the neonatal intensive care unit (NICU) can aid in screening infants with signs and symptoms of generalized illness. Cultures of blood, urine, and cerebrospinal fluid are the main diagnostic tools available in this population of infants, but several biomarkers and alternate identification methodologies such as 1,3-β-D-glucan, serum mannan or anti-mannan, and T2 magnetic resonance testing are being studied in the neonatal population. Prompt diagnosis of Candida infection, in conjunction with a comprehensive assessment of disease progression and organ involvement, is critical for optimizing treatment and patient outcomes. Supportive care and systemic antifungal medications remain the mainstay of treatment, and the efficacy and safety of newer therapeutic agents continue to be evaluated in neonates. Disease prevention strategies must be thoughtfully implemented and customized to each individual NICU based on local incidence of Candida infection, practice patterns, and risk factors, and may include prophylactic antifungal therapy. This review summarizes the evidence for current approaches to diagnosis and management of neonatal invasive candidiasis and provides an overview of the newer diagnostic tools and therapeutic agents on the horizon.Keywords: Candida, infant, biomarkers, amphotericin B, fluconazole, prophylaxis

الملخص: أهداف البحث: يعتبر التحول ثنائي الشكل من خلايا الخميرة إلى الواصلة أحد عوامل الفوعة الرئيسية للأنواع الخنية. في كثير من الأحيان تم الإبلاغ عن تطور المقاومة المضادة للفطريات ضد العديد من أمراض المبيضة. وبالتالي، فإن مزيجا من مضادات الفطريات المسجلة ذات المركبات النشطة بيولوجيا المشتقة من النبات قد تعزز الفعالية ضد العلاج الفطري. في هذه الدراسة، كنا نهدف إلى تحديد تأثير الهيدروكسي شافيكول، الأمفوتريسين ب ، والاثنين معا على انتقال وإنبات أنواع المبيضات الفموية. طريقة البحث: قابلية مضادات الفطريات لهيدروكسي شافيكول والأمفوتريسين ب بشكل منفصل والاثنين معا ضد المبيضة البيضاء،والمبيضة المرطية، والمبيضة المدارية. تقنية ''مايكرودايليوشن''. تم حساب الحد الأدنى من التركيز المثبطة بناء على بروتوكولات معهد المعايير السريرية والمخبرية. تم تحديد التركيز الأدنى المثبط اللازم لكبح 50%، مؤشر تركيز الكسور، و التركيز التثبيطي اللازم لكبح 50% أيضا. تم استخدام قيم التركيز التثبيطي 50% كتركيز علاجي لهيدروكسي شافيكول والأمفوتريسين ب بشكل منفصل والاثنين معا لدراسة تأثير تثبيط مضادات الفطريات على انتقال الخميرة هيفا. تم حساب نسبة تكوين أنبوب الجرثومة لأنواع المبيضات على عدة فترات باستخدام اختبار اللون. النتائج: كان الحد الأدنى من التركيزات المثبطة 50 مجموعة من الهيدروكسي شافيكول وحدها ضد أنواع المبيضات بين 120-240 ميكروغرام لكل مل بينما كان الأمفوتريسين بما بين 2-8 ميكروغرام لكل مل، على التوالي. أظهر مزيج من هيدروكسي شافيكول + الأمفوتريسين ب في 1: 1 و 2: 1 أقوى نشاط تآزري ضد المبيضة البيضاء. علاوة على ذلك، في غضون الساعة الأولى من العلاج، انخفضت النسبة المئوية الإجمالية للخلايا الإنبات بشكل كبير بنسبة 79 ٪. الاستنتاجات: أظهر مزيج من هيدروكسي شافيكول + الأمفوتريسين ب التآزر ومنع نمو المبيضة البيضاء. أبطأت مجموعةهيدروكسي شافيكول + الأمفوتريسين ب عملية الإنبات وأظهرت تأثيرا طويلا متسقا حتى 3 ساعات بعد العلاج. سوف تمهد نتائج هذه الدراسة الطريق لامكانية فرض هذه الدراسات على الجسم الحي. Abstract: Objectives: Dimorphic transformation from yeast cells to hyphae is considered one of the major virulence factors of candidal species. The development of antifungal resistance against several candida diseases has led researchers to find plant derived alternatives. We aimed to determine the effect of hydroxychavicol (HC), Amphotericin B (AMB), and their combination (HC + AMB) on the transition and germination of oral Candida species. Methods: The antifungal susceptibility of hydroxychavicol (HC) and Amphotericin B (AMB) separately and in a mixture (HC + AMB) against Candida albicans ATCC 14053, Candida parapsilosis ATCC 22019, Candida tropicalis ATCC 13803, and Candida dubliniensis ATCC MYA-2975 was determined by broth microdilution technique. Minimal Inhibitory Concentration was calculated based on the CLSI protocols. The MIC50, fractional inhibitory concentration (FIC) index, and IC50 were also determined. The IC50 values were used as the treatment concentration of HC, AMB, and HC + AMB to study the effect of antifungal inhibition on yeast hypha transition (gemination). The germ tube formation percentage of candida species was calculated at several intervals using a colorimetric assay. Results: The MIC50 range of HC alone against Candida species was between 120-240 µg per mL while that of AMB was between 2-8 µg per mL, respectively. The combination of HC + AMB at 1:1 and 2:1 demonstrated the strongest synergistic activity against C. albicans with an FIC index of 0.07. Moreover, within the first hour of treatment, the total percentage of germinating cells was significantly reduced by 79% (p < 0.05). Conclusion: The combination of HC + AMB displayed synergism and inhibited C. albicans hyphal growth. HC + AMB combination slowed the germination process and exhibited consistent prolonged effect up to 3 h post-treatment. The results of this study will pave the way for potential in vivo studies.

Background Focused efforts of the visceral leishmaniasis elimination program have led to a drastic decline in cases, and the present challenge is disease monitoring, which this study aimed to assess. Methods A Leishmania kinetoplastid-targeted qPCR quantified parasite load at disease presentation, and following treatment completion (n=49); an additional 80 cases were monitored after completion of treatment. Results The parasite load at disease presentation was 13 461.00 (2560.00–37764.00)/µg gDNA, which upon completion of treatment reduced in 47 of 49 cases to 1(1–1)/µg gDNA, p<0.0001. In 80 cases that presented >2 months post-treatment, their parasite burden similarly decreased to 1(1–1)/µg gDNA except in 6 of 80 cases, which were qPCR positive. Conclusion In 129 cases of visceral leishmaniasis, qPCR by quantification of parasite burden proved effective for monitoring treatment. [ABSTRACT FROM AUTHOR]

This case report discusses a rare and severe complication of COVID-19 recovery -- renal mucormycosis leading to right renal artery pseudoaneurysm. A 59-year-old patient, previously treated for COVID-19, presented with dry cough, flank pain, and hematuria. He was diagnosed with renal artery pseudoaneurysm with renal mucormycosis. Successful management included urgent angioembolization, systemic liposomal amphotericin B, and subsequent radical nephrectomy post-stabilization. The case underscores the importance of vigilant post-COVID-19 follow-up, particularly in patients treated with steroids, and highlights the need for a multidisciplinary approach for timely diagnosis and effective management of mucormycosis related complications. [ABSTRACT FROM AUTHOR]

Hyalohyphomycosis includes infections caused by various fungal species that produce hyaline, septate, branched hyphae. Fusarium is one such species which usually causes multiple papulo-nodules, ecthyma gangrenosum-like ulcers in immunocompromised individuals. Also, fusariosis is usually difficult to manage and responds favorably to amphotericin B, voriconazole, and posaconazole in disseminated cases. Here, we report an atypical case of cutaneous fusariosis in an immunocompetent individual who presented with multiple large cystic swellings, psoriasiform plaques, and palmoplantar keratoderma, and the patient responded completely to itraconazole. [ABSTRACT FROM AUTHOR]

The Candida haemulonii complex includes emerging opportunistic human fungal pathogens with documented multidrug-resistance profiles. It comprises Candida haemulonii sensu stricto, Candida haemulonii var. vulnera, Candida duobushaemulonii, Candida pseudohaemulonii, and Candida vulturna. In recent years, rates of clinical isolation of strains from this complex have increased in multiple countries, including China, Malaysia, and Brazil. Biofilm formation, hydrolytic enzymes, surface interaction properties, phenotype switching and cell aggregation abilities, extracellular vesicles production, stress response, and immune evasion help these fungi to infect the host and exert pathological effects. Multidrug resistance profiles also enhance the threat they pose; they exhibit low susceptibility to echinocandins and azoles and an intrinsic resistance to amphotericin B (AMB), the first fungal-specific antibiotic. AMB is commonly employed in antifungal treatments, and it acts via several known mechanisms. Given the propensity of clinical Candida species to initiate bloodstream infections, clarifying how C. haemulonii resists AMB is of critical clinical importance. This review outlines our present understanding of the C. haemulonii complex’s virulence factors, the mechanisms of action of AMB, and the mechanisms underlying AMB resistance.

Cutaneous leishmaniasis (CL) poses a significant public health concern in endemic regions due to its increasing prevalence and substantial impact on affected individuals. This disease is primarily caused by the Leishmania protozoa, which are transmitted through insect bites, and it manifests as a range of symptoms, from self-healing lesions to severe disfigurement. Current treatments, which often involve the parenteral administration of antimonials, face challenges such as poor compliance and adverse effects. This study investigates the efficacy of topical formulations containing meglumine antimoniate (MA) and amphotericin B (AmB), using Sepigel as an excipient, for treating CL. In the in vivo study, BALB/c mice infected with L. amazonensis developed lesions at the injection site five weeks post-infection. Subsequently, the mice were divided into eight groups: untreated mice, mice treated orally with miltefosine, mice treated intraperitoneally with MA, and mice treated topically with 15%, 22.5%, and 30% MA-Sepigel, as well as those treated with AmB-Sepigel. Treatments were applied daily for two weeks, and the results revealed a significant reduction in lesion size and parasite burden following topical application, particularly with the AmB-Sepigel formulations and 30% MA-Sepigel. Additionally, Sepigel-based treatments demonstrated improved patient compliance and reduced toxicity compared to systemic therapies. These findings underscore the potential of Sepigel-based formulations as a promising alternative for CL treatment. They offer enhanced efficacy and tolerability, while reducing the systemic toxicity associated with conventional therapies.

ObjectivesLiposomal amphotericin B (L-AMB) and isavuconazonium sulphate are commonly used antifungal drugs to treat mucormycosis. However, the efficacy of combination therapy of L-AMB/isavuconazonium sulphate versus monotherapy is unknown. We used an immunosuppressed mouse model of pulmonary mucormycosis to compare the efficacy of L-AMB/isavuconazonium sulphate versus either drug alone.MethodsNeutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with L-AMB, isavuconazonium sulphate, or a combination of both started 8 h post-infection and continued through to Day +4. Placebo mice received vehicle control. Survival to Day +21 and tissue fungal burden (by conidial equivalent using quantitative PCR) on Day +4, served as primary and secondary endpoints, respectively.ResultsFor mice infected with R. delemar, L-AMB and isavuconazonium sulphate equally prolonged median survival time and enhanced survival versus placebo (an overall survival of 50% for either drug alone, versus 5% for placebo). Importantly, combination treatment resulted in an overall survival of 80%. Both antifungal drugs reduced tissue fungal burden of lungs and brain by ∼1.0-2.0 log versus placebo-treated mice. Treatment with combination therapy resulted in 2.0-3.5 log reduction in fungal burden of either organ versus placebo and 1.0 log reduction versus either drug alone. Similar treatment outcomes were obtained using mice infected with M. circinelloides.ConclusionsThe L-AMB/isavuconazonium sulphate combination demonstrated greater activity versus monotherapy in immunosuppressed mice infected with either of the two most common causes of mucormycosis. These studies warrant further investigation of L-AMB/isavuconazonium sulphate combination therapy as an optimal therapy of human mucormycosis.

Ye J, Li R, Cheng J, et al. Int J Nanomedicine. 2022;17:6047–6064. The authors have advised that there is an error in Figure 9 on page 6060 of the published paper. Due to an error that occurred inadvertently at the time of figure assembly, figure part D is incorrect. Although it does not affect the conclusion that AmB nanoformulations can significantly promote macrophage proliferation when incubated with high concentrations, it is an obvious mistake. The correct Figure 9 is as follows. Figure 9 Continued. Figure 9 In vitro cytotoxicity of AmB injection, AmB-CSC, and AmB-Lipo in murine RAW264.7 macrophages. The murine RAW264.7 macrophages were treated with AmB injection (A), AmB-CSC (C), and AmB-Lipo (E) at AmB concentrations of 0.1–50 µg/mL for 24 h and the cell viability was determined using CCK-8 kits. Each value represents the mean ± SEM (n = 6). ***p < 0.001 compared with the control (Ctrl) group. The cell morphology of RAW264.7 macrophages after incubation with AmB injection (B), AmB-CSC (D), and AmB-Lipo (F) was observed by Cell Imaging Multimode Reader (Cytation 5, BioTek).Abbreviations: AmB, amphotericin B; AmB-CSC, AmB cholesteryl sulfate complex; AmB-Lipo, AmB liposome; SEM, standard error of the mean. The authors apologise for this error.

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

Purpose: This study aimed to evaluate the efficacy and safety of McCarey-Kaufman (MK) medium supplemented with colistin and amphotericin B in inhibiting the growth of multidrug-resistant Pseudomonas (P.) aeruginosa, using an ex vivo experimental model with human donor corneas. Methods: Cadaveric human corneas deemed unsuitable for corneal transplantation were obtained, and MK media were supplemented with colistin and amphotericin B. Multidrug-resistant P. aeruginosa was cultured and used to infect the human donor corneas ex vivo. Infected corneas were placed in the MK media with additional antibiotics (colistin and amphotericin B) and the standard MK media, which served as the control arm for comparison. Corneal opacity due to infiltration and quantitative analysis of colony-forming units (CFUs) were assessed. The viability of the corneal endothelium was assessed using trypan blue staining. Results: Corneas incubated in MK media supplemented with additional antibiotics showed less corneal opacification compared with those in standard MK media at both 48- and 96-hour (hr) time points. Quantitative analysis revealed a lower bacterial load and a significant reduction in CFU in the corneas incubated in MK media with additional antibiotics compared with the control group. At 48 hrs, there was 84% (P value = 0.024) reduction in bacterial load, and at 96 hr, a 53% (P value = 0.016) reduction was observed in comparison with those placed in standard MK media. The trypan blue staining tests revealed that the extent of endothelial cell loss in corneas incubated in supplemented MK media was comparable to the ones in standard MK media. Conclusion: The addition of colistin and amphotericin B to MK media demonstrated efficacy in inhibiting the growth of multidrug-resistant P. aeruginosa in an ex vivo cornea infection model. The supplemented media had no detrimental effect on the corneal endothelium. The findings suggest that supplementing the MK media with these broad-spectrum antimicrobial agents may help mitigate the risk of postoperative donor-related infection in the recipients by reducing and containing the load of microbial contamination in donor corneas.

Rhino- orbital-cerebral mucormycosis is a rapidly progressive life-threatening fungal infection which primarily affects the nose, paranasal sinuses and orbit. It is an opportunistic fungal infection caused by fungi of order Mucorales. They are a group of ubiquitous fungi which grow on decaying vegetation and a wide variety of organic compounds, and they pose a huge threat to life by direct invasion of the vital structures in the body. Early identification and treatment of this disease is therefore of paramount importance for a better outcome. We report a case of a 65-year-old man with a background history of poorly controlled type 2 diabetes mellitus, hypertension and chronic kidney disease, who presented with a diffuse headache of 5 days along with left sided facial oedema, redness of left eye and visual disturbance. Imaging studies revealed sinusitis involving multiple sinuses and the nasal mucosal biopsy showed fungal hyphae. Considering the clinical presentation and the overall findings from the investigations a diagnosis of rhino-cerebral mucormycosis was made. Medical management was done with administration of intravenous Amphotericin B and IV itraconazole along with other supportive medication. Patient had a successful recovery after a lengthy hospital stay which included surgical debridement of affected tissues and the medical treatment even with challenges faced due to unavailability of drugs due to economic constraints on health.

Aspergillosis is an infrequent infection in the Central Nervous System with a mortality rate higher than 95 %. Early diagnosis is challenging and crucial. In this report, we present the case of a six-year-old female with an intense headache accompanied by left hemiparesis, gaze deviation, horizontal nystagmus, and vomiting of mucous content on five occasions. After several approaches, a cerebrospinal fluid PCR resulted positive for Aspergillus spp., and then management started with amphotericin B at 2.6 mg/kg/day and was managed to have voriconazole. She survived, and two years after her first hospital admission, she suffered from cerebral aspergillosis sequelae. An area of improvement is the coordination between the request and delivery of studies outside the institution. In this case, the patient´s mother did not report the analysis results on time, delaying the diagnosis.

Introduction: Pityriasis versicolor (PV) often exhibits recurrence even despite treatment, and a standardized therapy with a complete cure rate remains elusive. Given the fungicidal property of amphotericin B, its potential for PV treatment warrants investigation. Objectives: This study aimed to compare the efficacy of topical liposomal amphotericin B and clotrimazole cream in treating PV. Methods: A randomized controlled trial was conducted with 44 PV patients, aged 15 to 70 years, who were equally assigned to either the amphotericin or clotrimazole group. The trial was registered at the Iranian Registry of Clinical Trials on March 7th, 2022. PV diagnosis was confirmed in all patients through positive microscopic results. The amphotericin group received topical gel containing liposomal amphotericin B 0.4%, while the other group received topical cream containing clotrimazole 1%. Both treatments were applied twice daily to the affected skin lesions for 14 days. The primary outcomes assessed were mycologic cure, clinical cure, and complete cure at day 14 post-treatment. Results: Both drugs demonstrated successful treatment outcomes, with comparable rates of mycologic cure (77.3%), clinical cure (63.6%), and complete combined cure (63.6%). There was no significant difference between the groups in terms of the degree of cure (P=0.75). Adjustments for age, sex, lesion extent, and lesion site yielded insignificant risk ratio and risk difference estimates for the complete cure rate (P>0.05). Conclusions: The topical application of liposomal amphotericin B 0.4% is equally effective as topical clotrimazole 1% in treating pityriasis versicolor. These findings suggest that liposomal amphotericin B could be considered as a viable alternative treatment for PV. Further research is warranted to explore its long-term consequences and safety profile.