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Nonionic‐surfactants have been reported as nanocarriers for delivering low bioavailable drugs at the target sites. In the current study, two new nonionic surfactants were synthesized to enhance the oral bioavailability of the low water‐soluble antifungal drug Amphotericin‐B. The hemolysis effect of nonionic surfactants on red blood cells and cytotoxicity against the 3T3 cell line was studied. Both surfactants have shown low hemolysis and cytotoxicity as compared to standard Tween 80. The morphology of drug‐loaded niosomes of nonionic surfactants 1 and 2 was studied by using atomic force microscopy (AFM), and both surfactants based vesicles were spherical, while their average sizes were measured by dynamic light scattering (DLS). The average size, zeta potential and polydispersity index (PDI) values of surfactants 1 and 2 were 282 ± 3 nm, −8 ± 1 mV, 0.26 and 287 ± 3 nm, −10 ± 1 mV, 0.24. The drug entrapment efficiency and critical micelle concentrations of nonionic surfactants were determined by using UV–visible spectroscopy. The structures of surfactants 1 and 2 were assessed through single‐crystal x‐ray crystallographic analysis, while Hirshfeld analysis was performed to study the intermolecular interactions of molecules, as well as the packing behavior of their crystals. The nonionic‐surfactant 1 was further tested for antileishmanial activity against Leishmania tropica promastigotes, in both drug‐loaded and unloaded niosomal vesicular forms. The nonionic surfactant 1 was found to be a potentanti‐leishmanial agent in the drug‐loaded form with IC50 = 3.02 ± 0.91 μM in comparison to their standard drugs Amphotericin‐B (IC50 = 3.8 ± 0.04 μM) and miltefosine (IC50 = 42.2 ± 0.6 μM) (p < 0.1). These results, therefore, form the basis of further results towards efficient drug delivery against tropical disease Leishmaniasis. [ABSTRACT FROM AUTHOR]

Airway mucormycosis is a fatal opportunistic infection typically seen in immunocompromised individuals. In this case report, we present an unusual instance of tracheal stenosis in a patient with diabetes mellitus who had recently recovered from coronavirus 2019 (COVID-19). Our patient was a 69-year-old male with poorly controlled type-II diabetes mellitus, on oral hypoglycemic agents, who had successfully completed treatment for COVID-19. Approximately one month later, he developed a cough, fever and breathlessness. Several factors, including advanced age, history of smoking and tobacco chewing, the nodular appearance of the trachea on bronchoscopy, hypermetabolic wall of the trachea on positron emission tomography scan and dysplasia on biopsy, initially raised suspicion of malignancy. However, repeated biopsies from multiple sites confirmed the diagnosis of tracheal mucormycosis. The patient was treated with amphotericin-B and posaconazole. We extensively reviewed the literature and found only 14 reported cases to discuss compared to ours.

Airway mucormycosis is a fatal opportunistic infection typically seen in immunocompromised individuals. In this case report, we present an unusual instance of tracheal stenosis in a patient with diabetes mellitus who had recently recovered from coronavirus 2019 (COVID-19). Our patient was a 69-year-old male with poorly controlled type-II diabetes mellitus, on oral hypoglycemic agents, who had successfully completed treatment for COVID-19. Approximately one month later, he developed a cough, fever and breathlessness. Several factors, including advanced age, history of smoking and tobacco chewing, the nodular appearance of the trachea on bronchoscopy, hypermetabolic wall of the trachea on positron emission tomography scan and dysplasia on biopsy, initially raised suspicion of malignancy. However, repeated biopsies from multiple sites confirmed the diagnosis of tracheal mucormycosis. The patient was treated with amphotericin-B and posaconazole. We extensively reviewed the literature and found only 14 reported cases to discuss compared to ours. [ABSTRACT FROM AUTHOR]

The most prevalent conditions among ocular surgery and COVID−19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Aim: To study the role of retrobulbar (intraorbital) injection of amphotericin-B in the management of orbital mucormycosis. Materials and Methods: Patients with nasal diagnostic endoscopy or imaging confirmed, orbital mucormycosis were given 3 doses of 3.5 mg/ml of retrobulbar injection amphotericin-B for 3 alternate days and followed up for 72 hours for progression of symptoms. Results: Out of total 696 in-patients, 464 were males (66%) and 232 were females (34%), 612 were diabetic (88%), 490 were covid positive (71%), 308 patients have taken steroid (45%), 205 patients were given oxygen (30%). Out of 696 in-patients, 312 (45%) were started on retrobulbar injection of amphotericin. Dose wise-out of 312 retrobulbar injections, less than 3 doses is given for 69 patients (22%), 3 doses completed for 243 patients (78%). Outcomes-out of 243 three dose completed patients,49 (20%) patients has shown improvement in terms of vision and symptoms, 172 (71%) patients were stable without progression, 64 (26%) patients have shown deterioration out of which 35 patients progressed rapidly and undergone exenteration and remaining 29 are under observation. Conclusion: Retrobulbar injection of amphotericin-B along with iv amphotericin and sinus debridement through FESS have shown improvement and also halted the progression. Patients in stage 3a and 3b have shown better outcome with retrobulbar injection of amphotericin-b than in stage 3c and 3d.

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted. [ABSTRACT FROM AUTHOR]

A series of novel (1-phenyl-1H-1,2,3-triazol-4-yl)methyl-2-acetamido-1-phenyl-1H-benzo[f] benzo[f]chromene-3-carboxylate 6a-i compounds have been synthesised from prop-2-yn-1yl-3-acetamido-1-phenyl-1H-benzo[f]chromene-2-carboxylate 5. 3-Amino-1-phenyl-1H-benzo[f]chromene-2-carbonitrile and 2-amino-4-phenyl-4a,5,6,7,8,8a-hexahydro-4Hchromene-3-carbonitrile (1 and 2a) are generated when benzaldehyde, β-naphthol, (or) cyclohexanol, and malononitrile are incorporated into the mixture. Activity of two conventional antibiotics, Chloramphenicol and Amphotericin-B, have been compared to the antibacterial and antifungal properties of the prepared synthetic compounds. A study has been conducted on the spectroscopic properties of Schlenter products. [ABSTRACT FROM AUTHOR]

To study clinicoepidemiology and surgical complications in acute invasive fungal rhinosinusitis. Retrospective observational study carried in GMC Akola from February 2021 to April 2022. Detailed history and clinical examination, nasal endoscopic biopsy or swab for KOH and fungal culture was taken. CECT/MRI PNS + Orbit + Brain was done. All patients underwent surgery and tissue sample send for histopathological examination. Total 146 patients included in study with M:F ratio 1.7:1. Most affected age group was between 40 and 60 years. 107 (78.6%) patients had history of COVID-19.Mucorale is most commonly found fungal species (90.4%) followed by aspergillus (2.7%) & mixed species (6.8%). Diabetes Mellitus is most common comorbidity. Intraoperative complications were bleeding (72.60%), CSF leak (4.1%), orbital hematoma (0.68%), nasolacrimal duct trauma (2.05%), periorbital hematoma (0.68%). Post operative complications like synechiae (56.16%), OAF (45.89%), hypoesthesia (25.34%), decreased vision (16.43%), facial pain (20.54%), facial deformity (20.54%), diplopia (6.8%), headache (30.13%), anosmia (39.72%), dental pain (20.54%), earache (9.58%), hyposmia (45.89%), periorbita ecchymosis (0.68%), residual disease (16.10%), recurrence (2.05%), death (2.05%) was observed. Prompt surgical debridement of devitalized tissue and early adequate dosage of antifungal (inj. Amphotericin-b) treatment are necessary as delay in surgical debridement and treatment can worsen the prognosis of disease. Among all complications faced maximum were manageable with early interventions but few of them were inevitable due to extensive nature of disease. [ABSTRACT FROM AUTHOR]

Oral fungal infections are frequently encountered in clinical practice, and with the advent of the Coronavirus disease 2019 (COVID-19) pandemic, their incidence has quite increased. Increased emergence of oral candidal and non candidal infections is evident in patients with uncontrolled diabetes, patients on steroids or antibiotic therapies, and immunocompromised and immunosuppressed individuals. Also, habits of smoking and alcohol consumption, intake of carbohydrate-rich food, and salivary dysfunction have many times influenced the colonisation of fungal infections in the oral cavity. Aspergillosis once considered exotic is now more prevalent than before and presents itself in two forms: non invasive or invasive form, which has led to the rapid dissemination of the disease. Hence, a timely diagnosis of such lesions is important to prevent their invasion into other parts of the body. This article discusses a rare case report of Aspergillosis occurring in the oral cavity at the site of the extraction socket in a 50-year-old woman, who is a known diabetic without any history of COVID-19 infection. Aspergillosis unlike other fungal infections of the oral cavity has been reported more in immunocompetent individuals. Here, we report a unique case limited to the oral cavity in an immunocompromised patient.

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

In this study, amphotericin-B (AMB)-loaded sodium alginate (SA) nanoparticles were fabricated using the electrospraying technique for biomedical applications. AMB is an antifungal agent and is poorly absorbed from the gastrointestinal tract due to its low aqueous solubility. Therefore, it should be given parenterally to treat systemic fungal infections. This study aims to transport it with nanoparticle formulations and observe the nanoparticle release behaviours. Scanning electron microscopy (SEM) images showed that nanoparticles of 0.5% SA fabricated at 37 kV had the most suitable particle diameter (93.36 ± 24.386 nm) for loading 0.5, 1, and 3 ml of AMB. Fourier transform infrared spectroscopy (FTIR) results demonstrated that AMB successfully loaded into 0.5% SA nanoparticles. Drug release behaviours of the AMB-loaded particles indicated that AMB was released with a burst at the beginning, and release behaviour became sustainable after half an hour. The encapsulation efficiencies of the different amounts of drug were calculated, and the results showed that the highest encapsulation efficiency belonged to the 0.5% SA/1 AMB nanoparticles (42 ± 1.23%). [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) pandemic is currently evolving and associated with more complications with invasive fungal infection like mucormycosis. Classically, uncontrolled diabetes mellitus (DM) and other immunosuppressive conditions like corticosteroid therapy are known risk factors for causing mucormycosis in COVID-19 patients. Mucormycosis is an invasive fungal infection which rapidly spread to the orbit and brain from the nasal cavity and paranasal sinuses. Mucormycosis in COVID-19 is a fatal to the patient. There is possibility of COVID-19 as a trigger factor for diabetic ketoacidosis which predisposes to invasive fungal infections such as mucormycosis. Patients with poorly controlled DM and immunocompromised conditions increase the risk for development of COVID-19 infections in COVID-19 patients. During the current COVID-19 pandemic, a myriad of clinical manifestations and complications are emerged. Rhino-orbital-cerebral mucormycosis is a fatal clinical entity associated with COVID-19 infections resulting in higher morbidity and mortality. The treatment includes both medical and surgical interventions. It requires early and adequate treatment with amphotericin B and surgical debridement and control of risk factors. A multidisciplinary approach by otorhinolaryngologists, ophthalmologists, neurologists, and dentists is successful for treatment of COVID-19 patients with mucormycosis in the head-and-neck region. Identification of the risk factors and early preventive measures will minimize the incidence of life-threatening mucormycosis in the head-and-neck area of COVID-19 patients.

Surge in the number of mucormycosis cases following second wave of coronavirus disease-19 (COVID-19) infection posed several diagnostic and prognostic challenges. This study was aimed to describe clinical, diagnostic features and survival outcomes among patients of mucormycosis in post COVID-19 context. Retrospective chart review. This study included 44 COVID-19 positive screened cases who presented with clinical features suggestive of mucormycosis. Demography, clinical profile, diagnostic findings, and the treatment outcome are studied. Medical and surgical outcomes are summarised as frequencies and percentages. The reliability of microbiological, and radiological findings against the pathological findings was analyzed using Kappa statistics (k). Based on constellation of microbiological, pathological and radiological findings 28 cases (63%) confirmed with mucormycosis infection. The mean (SD) age was 54.9 (12.9) years and two-third were males. The majority (90%) of cases presented with the feature of facial swelling, headache nasal blockade. Inpatient care for treatment of COVID-19 was recorded in 33 (75%). Diabetes mellitus was the commonest comorbidity in 27 (61.4%), 38 (86.4%) cases were treated by steroids and 30 (68.2%) were given oxygen therapy. There is a strong agreement (k = 0.83) between pathological and microbiological investigations. In thirty-eight cases (86.3%) remission was achieved when assessed after 8 weeks. Of the 44 cases, four patients died. The results of the current study suggest that the disease residues and/or recurrences in critical areas are frequent in mucormycosis. However, using the strategy of screening at risk patients, diagnosing, treating them with combination of antifungals, surgical debridement, and timely follow up may help in improving outcomes as compared to pre COVID-19 era. [ABSTRACT FROM AUTHOR]

Mucormycosis is a life threatening, opportunistic infection often seen in individuals with a weak immune system. With an upsurge of cases of Covid-19, a drastic increase in cases of Rhino-Orbito-Cerebral Mucormycosis is being witnessed at present. This article has been written with the purpose of understanding the factors responsible for it and the challenges it brings along for the Indian health-care system at present. Possible solutions for dealing with these problems have also been included in the manuscript. Google, PubMed and ENT Cochrane databases were searched without a time limit using key words like "Mucormycosis", "Rhino-cerebral-mucormycosis" in conjunction with "COVID-19" and "SARS CoV-2". We found 34 articles to be relevant and hence included them to write this review. Rhino-Orbito-Cerebral Mucormycosis is being seen due to coming together of the three entities-the agent, host and environment that constitute the epidemiological triad for this disease in India. Responsible factors are uncontrolled diabetes mellitus, overzealous use of steroids and antibiotics and other environment related issues. The solutions for these problems lie in spreading awareness about prevention of these practices along with early diagnosis and treatment of mucormycosis. To deal effectively with this situation, particularly when there is an existing overload on otolaryngologists and the rest of the health-care system, a multipronged and multilevel collaborative approach is the need of the hour. With effective Standard Operating Procedures and guidelines promoting a multidisciplinary approach for early diagnosis and treatment, we can surely overcome this situation. [ABSTRACT FROM AUTHOR]

Rhino orbital cerebral mucormycosis is a medical emergency; though rare it's a life threatening infection in patients. It commonly occurs in immunocompromised patients due to various causes. A retrospective study was conducted in tertiary care centre wherein 30 non-covid, diabetic patients were treated for mucormycosis. All underwent intensive debridement and diabetic management along with antifungal- amphotericin. All the cases improved with aggressive therapy: medical and surgical. Early recognition and treatment is needed to prevent morbidity and mortality. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) pandemic is currently evolving and associated with more complications with invasive fungal infection like mucormycosis. Classically, uncontrolled diabetes mellitus (DM) and other immunosuppressive conditions like corticosteroid therapy are known risk factors for causing mucormycosis in COVID-19 patients. Mucormycosis is an invasive fungal infection which rapidly spread to the orbit and brain from the nasal cavity and paranasal sinuses. Mucormycosis in COVID-19 is a fatal to the patient. There is possibility of COVID-19 as a trigger factor for diabetic ketoacidosis which predisposes to invasive fungal infections such as mucormycosis. Patients with poorly controlled DM and immunocompromised conditions increase the risk for development of COVID-19 infections in COVID-19 patients. During the current COVID-19 pandemic, a myriad of clinical manifestations and complications are emerged. Rhino-orbital-cerebral mucormycosis is a fatal clinical entity associated with COVID-19 infections resulting in higher morbidity and mortality. The treatment includes both medical and surgical interventions. It requires early and adequate treatment with amphotericin B and surgical debridement and control of risk factors. A multidisciplinary approach by otorhinolaryngologists, ophthalmologists, neurologists, and dentists is successful for treatment of COVID-19 patients with mucormycosis in the head-and-neck region. Identification of the risk factors and early preventive measures will minimize the incidence of life-threatening mucormycosis in the head-and-neck area of COVID-19 patients. [ABSTRACT FROM AUTHOR]

The second wave of coronavirus disease 2019 (COVID-19) caused severe infections with high mortality. An increase in the cases of COVID-19-associated mucormycosis (CAM) was reported predominantly in India. Commonly present in immunocompromised individuals, mucormycosis is often a life-threatening condition. Confounding factors and molecular mechanisms associated with CAM are still not well understood, and there is a need for careful research in this direction. In this review, a brief account of the diagnosis, management, and advancement in drug discovery for mucormycosis has been provided. Here, we summarize major factors that dictate the occurrence of mucormycosis in COVID-19 patients through the analysis of published literature and case reports. Major predisposing factors to mucormycosis appear to be uncontrolled diabetes, steroid therapy, and certain cancers. At the molecular level, increased levels of iron in COVID-19 might contribute to mucormycosis. We have also discussed the potential role and regulation of iron metabolism in COVID-19 patients in establishing fungal growth. Other factors including diabetes prevalence and fungal spore burden in India as contributing factors have also been discussed. [ABSTRACT FROM AUTHOR]

The second wave of coronavirus disease 2019 (COVID-19) caused severe infections with high mortality. An increase in the cases of COVID-19-associated mucormycosis (CAM) was reported predominantly in India. Commonly present in immunocompromised individuals, mucormycosis is often a life-threatening condition. Confounding factors and molecular mechanisms associated with CAM are still not well understood, and there is a need for careful research in this direction. In this review, a brief account of the diagnosis, management, and advancement in drug discovery for mucormycosis has been provided. Here, we summarize major factors that dictate the occurrence of mucormycosis in COVID-19 patients through the analysis of published literature and case reports. Major predisposing factors to mucormycosis appear to be uncontrolled diabetes, steroid therapy, and certain cancers. At the molecular level, increased levels of iron in COVID-19 might contribute to mucormycosis. We have also discussed the potential role and regulation of iron metabolism in COVID-19 patients in establishing fungal growth. Other factors including diabetes prevalence and fungal spore burden in India as contributing factors have also been discussed.

The incidence of leishmaniasis is reported to be up to 1 million per year. To date, there has been no comprehensive review describing the diversity of clinical presentations of ocular leishmaniasis (OL) and its treatment. This systematic review aims to address this knowledge gap and provide a summary of the clinical presentation, natural course, and treatment options for OL. Our study identified a total of 57 published articles as describing cases of OL involving: adnexa (n = 26), orbit (n = 1), retina (n = 7), uvea (n = 18) and cornea (n = 6). Though well described and easily treated, palpebral leishmaniasis is often misdiagnosed and may lead to chronic issues if untreated. The retinal manifestations of Leishmaniasis consist of self-resolving hemorrhages secondary to thrombocytopenia. Two main uveitis etiologies have been identified: uveitis in the context of active Leishmanial infection (associated with immunosuppression) and uveitis occurring as an immune reconstitution syndrome. Corneal involvement in most geographic areas generally follows an aggressive course, most often ending in corneal perforation if left untreated. In the Americas, a chronic indolent interstitial keratitis may also occur. Topical steroids are of little use in keratitis (systemic antileishmanials being the cornerstone of treatment). However, these are essential in cases of uveitis, with or without concomitant systemic antileishmanial therapy. In conclusion, though ocular involvement in Leishmaniasis is rare, severe sight-threatening consequences follow if left untreated. Early diagnosis, enthusiastic follow-up and aggressive treatment are essential for good outcomes.

Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat Candida albicans infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. Cmin (pre-dose) and Cmax (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (p = 0.03) between plasma and peritoneal Cmin. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC > 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections. [ABSTRACT FROM AUTHOR]

Primary cutaneous cryptococcosis (PCC) is an uncommonly reported entity. We describe an unusual case of PCC in an injection site of an immunocompromised patient. The specific case demonstrates a challenging treating dilemma with different alternative treatment choices. In the presented clinical setting, each choice concealed its risks and benefits. We highlight the importance of patient education for taking the appropriate measures for the disinfection of subcutaneous injection sites.

Mostafa Chadeganipour,1 Rasoul Mohammadi1,2 1Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; 2Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, IranCorrespondence: Rasoul MohammadiAssociate Professor of Medical Mycology, Department of Medical Parasitology and Mycology, School of Medicine, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, IranTel +98-31-37929175Fax +98-31-36688597Email Dr.rasoul_mohammadi@yahoo.comPurpose: Aspergillosis is an important fungal disease affecting millions of individuals worldwide. The genus of Aspergillus consist of various complexes, causing a wide spectrum of diseases from superficial infections in immunocompetent hosts to life-threatening disseminated infections among immunocompromised patients. This study aimed to identify Aspergillus species by phenotypic (total isolates) and molecular tests (35 isolates), obtained from patients in Isfahan (the third-largest city of Iran) between 2010 and 2018, and determine the susceptibility of 35 clinical isolates to itraconazole (ITR), amphotericin-B (AMB), and voriconazole (VOR).Patients and Methods: Based on clinical signs, a total of 2385 suspected cases were included in this retrospective study from January 2010 to December 2018. Direct microscopic examination with potassium hydroxide, sabouraud dextrose agar with chloramphenicol, and czapekdox agar media was applied to identify etiologic agents. Thirty-five Aspergillus species collected from January 2016 to December 2018 were identified by PCR-sequencing of ITS1-5.8SrDNA-ITS2 region, and their susceptibility to ITR, AMB, and VOR was determined using E-test.Results: Based on direct microscopy and positive culture, 132 out of 2385 suspected cases had Aspergillus infection (5.5%). Fifty-four patients were male, and 78 patients were female. Patients in the age groups of 41– 50 and 21– 30 years had the highest and lowest frequencies, respectively. Aspergillus flavus/oryzae (n=54), A. fumigatus (n=24), A. niger (n=15), and A. terreus (n=12) were the most prevalent Aspergillus species, respectively. Among 35 Aspergillus species, the MIC ranges of AMB, ITR, and VOR for A. flavus/oryzae, A. niger, and A. terreus were (0.5– 4 μg/mL; 0.5– 16 μg/mL; 0.25– 8 μg/mL), (1 μg/mL, 1 μg/mL, 1 μg/mL), and (4– 4 μg/mL, 0.5– 1 μg/mL, 0.5– 1 μg/mL), respectively.Conclusion: Aspergillus infections have a wide spectrum of clinical manifestations and often occur in immunocompromised patients. Accurate identification at the species level is essential since the emergence of cryptic species is connected to different patterns of AFST that affect patient treatment outcomes. Azole-resistant Aspergillus spp. is a global concern, and the detection of the route of resistance is pivotal to prevent and control infection.Keywords: Aspergillus, causative agents, E-test, itraconazole, amphotericin-B, voriconazole

Corona Virus Disease (COVID-19) which has a common association with diabetes has led to an epidemic of mucormycosis which has been mainly attributed to rampant use of steroids owing to the severity of the disease. The mucormycosis patients presented with rhino orbital mucormycosis predominantly with or without intracranial extension making it a life-threatening condition mandating urgent debridement as treatment of choice alongside antifungal medications. Injection Amphotericin B is the first-line drug that is nephrotoxic and causes dyselectrolytemia therefore administered under strict supervision. However, we report successful management of two unique cases where patients after surgical debridement after Amphotericin B developed severe life-threatening anaemia postoperatively along with impending respiratory failure requiring Intensive care management including non-invasive ventilation. Thus, serial haematocrit monitoring is of utmost importance while the patient is being administered Amphotericin B even when a patient is receiving the relatively safe preparation that is liposomal Amphotericin B in a dose of 3.5 mg per kg body weight.

The Coronavirus outbreak globally has changed the medical system and also led to a shortage of medical facilities in both developing and underdeveloped countries. The COVID19 disease, being novel in nature along with high infectivity and frequent mutational rate, has been termed to be fatal across the globe. The advent of infection by SARS-CoV-2 has brought a myriad of secondary complications and comorbidities resulting in additional challenges to the health care system induced by novel therapeutic procedures. The emerging variant with respect to the Indian subcontinent and the associated genetic mutations have worsened the situation at hand. Proper clinical management along with epidemiological studies and clinical presentations in scientific studies and trials is necessary in order to combat the simultaneous waves of emerging strains. This article summarizes three of the major fungal outbreaks in India namely mucormycosis, candidiasis and aspergillosis, and elaborates their subtypes, pathogenesis, symptoms and treatment and detection techniques. A detail of future therapeutics under consideration are also elaborated along with a general hypothesis on how COVID19 is related to immunological advances leading to major widespread fungal infection in the country. The factors that contribute in promoting virus proliferation and invasive fungal infections include cell-mediated immunity, associated immunocompromised conditions and treatment protocols that slows down immune mechanisms. To better comprehend a fungal or bacterial outbreak, it is very important to conduct audits mediated through multicenter national and state research teams for recognizing patterns and studying current cases of fungal infection in both healthy and comorbid groups of COVID19 patients. [ABSTRACT FROM AUTHOR]

An upsurge in the cases of severe opportunistic infections such as mucormycosis has been observed due to Coronavirus Disease 2019 (COVID-19), that is a viral infection caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Even though it was a rare opportunistic infection, the incidence of this disease seems to be increasing with the emergence of COVID19 infection worldwide. Individuals are vulnerable to this secondary infection due to uncontrolled diabetes, coronavirus disease infection therapy, immunosuppression, and pre-existing co-morbidities. This case series aimed to report how aggressive and fatal mucormycosis can be in diabetic and immunocompromised cases as well as the outcome of its treatment protocol. Authors hereby have reported seven individuals treated at our institute, who were affected by COVID-19 a few months back, were long-term diabetics and then, developed mucormycosis. Removal of all devitalised tissue was the treatment protocol author followed, along with antifungal therapy. All the cases were monitored using clinical evaluation and Computed Tomography (CT). Amongst the seven individuals, five survived uneventfully with no recurrence of the infection.

An upsurge in the cases of severe opportunistic infections such as mucormycosis has been observed due to Coronavirus Disease 2019 (COVID-19), that is a viral infection caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Even though it was a rare opportunistic infection, the incidence of this disease seems to be increasing with the emergence of COVID-19 infection worldwide. Individuals are vulnerable to this secondary infection due to uncontrolled diabetes, coronavirus disease infection therapy, immunosuppression, and pre-existing co-morbidities. This case series aimed to report how aggressive and fatal mucormycosis can be in diabetic and immunocompromised cases as well as the outcome of its treatment protocol. Authors hereby have reported seven individuals treated at our institute, who were affected by COVID-19 a few months back, were long-term diabetics and then, developed mucormycosis. Removal of all devitalised tissue was the treatment protocol author followed, along with antifungal therapy. All the cases were monitored using clinical evaluation and Computed Tomography (CT). Amongst the seven individuals, five survived uneventfully with no recurrence of the infection. [ABSTRACT FROM AUTHOR]

Mucormycosis is an invasive fungal infection caused by a group of moulds or spores and specially effects the patients with low ability to fight against diseases. It is not contagious; it can be diagnosed with Computed tomography scan and new advancement in molecular tools are being developed. In this review mucormycosis pathology, diagnosis and its treatment with various antifungal drugs are discussed in brief. [ABSTRACT FROM AUTHOR]

Amphotericin B‐deoxycholate (Fungizone [FZ]) is a widely used potent antimycotic drug in spite of its nephrotoxic effect via different mechanisms. The effect of FZ on renal cell bioenergetics is not clear. The current study evaluated the effect of FZ on the bioenergetics of albino rats' isolated renal proximal tubule cells (PTCs). The cytotoxic effect of FZ on the isolated renal cells was assessed by MTT and lactate dehydrogenase (LDH) assays. The effect of FZ on the PTCs uptake (OAT1 and OCT2) and efflux (P‐gp and MRP2) transporters was evaluated. Then, the effect of FZ on mitochondria was assessed by studying complexes I–IV activities, lactate assay, oxygen consumption rates (OCR), and western blotting for all mitochondrial complexes. Moreover, the effect of FZ on mitochondrial membrane fluidity (MMF) and fatty acids composition was evaluated. Additionally, the protective effect of coenzyme q10 was studied. Outcomes showed that FZ was cytotoxic to the PTCs in a concentration and time‐dependent patterns. FZ significantly inhibited the studied uptake and efflux tubular transporters with inhibition of the mitochondrial complexes activities and parallel increase in lactate production and decrease in OCRs. Finally, FZ significantly reduced the expression of all mitochondrial complexes in addition to significant increase in MMF and MMFA concentration. Coenzyme Q10 was found to significantly decrease FZ‐induced cytotoxicity and transporters impairment in the PTC. FZ significantly inhibits bioenergetics of PTC, which may stimulate the cascade of cell death and clinical nephrotoxicity. Fungizone significantly inhibits mitochondrial bioenergetics of the renal proximal tubular cells with significant functional impairment. This mitochondrial dysfunction may stimulate the cascade of cell death and clinical nephrotoxicity. Coenzyme Q10 was found to significantly decrease Fungizone‐induced cytotoxicity and transporters impairment in the PTC. [ABSTRACT FROM AUTHOR]

Palatal involvement in mucormycosis is mostly secondary to rhino-orbito-cerebral disease, but rarely can be a primary disease of the oral mucosa. This report presents two rare cases of the isolated palatal mucormycosis in neutropenic children and highlights some of the peculiar features of the primary palatal disease and management-related issues in children. A 12-year-old child, who had completed the dexamethasone-based induction phase of chemotherapy for Near Early T cell precursor acute lymphoblastic leukemia, and a 9-year-old boy with a Late Isolated Medullary relapse of B cell acute lymphoblastic leukemia, who was to receive salvage induction chemotherapy, developed palatal discoloration without any other major complaints. Both had neutropenia and were on antifungal prophylaxis. In vitro staining of the discolored mucosa suggested mucormycosis, which was confirmed by pathological examination of the debrided tissue. Computed tomography, done before debridement, showed no significant sinonasal disease enabling us to proceed with the transoral approach. With the help of adjuvant antifungal therapy, the infection could be contained in both cases. This report, along with the reviewed literature, shows that limited palatal mucormycosis can be effectively treated by early diagnosis and debridement and appropriate antifungal therapy. Also, the role of antifungal prophylaxis amongst neutropenic patients has been briefly discussed here. [ABSTRACT FROM AUTHOR]

The supramolecular-based macrocyclic amphiphiles have fascinating attention and find extensive utilization in the pharmaceutical industry for efficient drug delivery. In this study, we designed and synthesized a new supramolecular amphiphilic macrocycle to serve as an efficient nanocarrier, achieved by treating 4-hydroxybenzaldehyde with 1-bromotetradecane. The derivatized product was subsequently treated with resorcinol to cyclize, resulting in the formation of a calix(4)-resorcinarene-based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized using mass spectrometry, IR, and 1H NMR spectroscopic techniques. The amphotericin-B (Amph-B)-loaded and unloaded amphiphiles were screened for biocompatibility studies, vesicle formation, particle shape, size, surface charge, drug entrapment, in-vitro release profile, and stability through atomic force microscopy (AFM), Zetasizer, HPLC, and FT-IR. Amph-B -loaded macrocycle-based niosomal vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle exhibited no cytotoxicity against normal mouse fibroblast cells and was found to be hemocompatible and safe in mice following an acute toxicity study. The drug-loaded macrocycle-based vesicles appeared spherical, nano-sized, and homogeneous in size, with a notable negative surface charge. The vesicles remained stable after 30 days of storage. The results of Amph-B oral bioavailability and pharmacokinetics revealed that the newly tailored niosomal formulation enhanced drug solubility, protected drug degradation at gastric pH, facilitated sustained drug release at the specific target site, and delayed plasma drug clearance. Incorporating such advanced niosomal formulations in the field of drug delivery systems has the potential to revolutionize therapeutic outcomes and improve the quality of patient well-being. [Display omitted] • A new supramolecular macrocyclic amphiphile was synthesized. • Supramolecular macrocyclic amphiphile have potential to encapsulate Amphotericin-B. • Macrocyclic amphiphile demonstrated sustained drug release behaviors at various pH. • Amphotericin-B loaded macrocyclic amphiphile exhibited oral bioavailability. [ABSTRACT FROM AUTHOR]

The incidence of leishmaniasis is reported to be up to 1 million per year. To date, there has been no comprehensive review describing the diversity of clinical presentations of ocular leishmaniasis (OL) and its treatment. This systematic review aims to address this knowledge gap and provide a summary of the clinical presentation, natural course, and treatment options for OL. Our study identified a total of 57 published articles as describing cases of OL involving: adnexa (n = 26), orbit (n = 1), retina (n = 7), uvea (n = 18) and cornea (n = 6). Though well described and easily treated, palpebral leishmaniasis is often misdiagnosed and may lead to chronic issues if untreated. The retinal manifestations of Leishmaniasis consist of self-resolving hemorrhages secondary to thrombocytopenia. Two main uveitis etiologies have been identified: uveitis in the context of active Leishmanial infection (associated with immunosuppression) and uveitis occurring as an immune reconstitution syndrome. Corneal involvement in most geographic areas generally follows an aggressive course, most often ending in corneal perforation if left untreated. In the Americas, a chronic indolent interstitial keratitis may also occur. Topical steroids are of little use in keratitis (systemic antileishmanials being the cornerstone of treatment). However, these are essential in cases of uveitis, with or without concomitant systemic antileishmanial therapy. In conclusion, though ocular involvement in Leishmaniasis is rare, severe sight-threatening consequences follow if left untreated. Early diagnosis, enthusiastic follow-up and aggressive treatment are essential for good outcomes. [ABSTRACT FROM AUTHOR]

In this report, we discuss the design of a novel collagen/pectin (CP) hybrid composite hydrogel (CPBG) containing in-situ mineralized bioactive glass (BG) particles to simulate an integrative 3D cell environment. Systematic analysis of the CP sol revealed collagen and pectin molecules interacted regardless of both possessing similar net negative charge through the mechanism of surface patch binding interaction. Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) confirmed this associative interaction which resulted in the formation of a hybrid crosslinked network with the BG nanoparticles acting as pseudo crosslink junctions. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Analysis (EDAX) and Transmission Electron Microscopy (TEM) results confirmed uniform mineralization of BG particles, and their synergetic interaction with the network. The in-vitro bioactivity tests on CPBG indicated the formation of bone-like hydroxyapatite (Ca 10 (PO 4) 6 (OH) 2) microcrystals on its surface after interaction with simulated body fluid. This hydrogel was loaded with a model antifungal drug amphotericin-B (AmB) and tested against Candida albicans. The AmB release kinetics from the hydrogel followed the Fickian mechanism and showed direct proportionality to gel swelling behavior. Rheological analysis revealed the viscoelastic compatibility of CPBG for the mechanical load bearing applications. Cell viability tests indicated appreciable compatibility of the hydrogel against U2OS and HaCaT cell lines. FDA/PI on the hydrogel portrayed preferential U2OS cell adhesion on hydrophobic hydroxyapatite layer compared to hydrophilic surfaces, thereby promising the regeneration of both soft and hard tissues. [ABSTRACT FROM AUTHOR]

Pulmonary mucormycosis is a rare and lethal fungal infection elicited by fungi of the order Mucorales. The disease predominantly affects immunocompromised hosts, like those with diabetes mellitus, hematologic malignancies, or those undergoing immunosuppressive therapy. We, at this moment, report a case of pulmonary mucormycosis in a 55-year-old gentleman, exemplifying the ferocity of clinical disease, diagnostic dilemmas, and rapidity of progression. A diagnosis of pulmonary mucormycosis was based on diagnostic imaging and flexible bronchoscopy. Despite aggressive antifungal and supportive treatment, the patient's condition deteriorated further, and unfortunately succumbed to cardiorespiratory arrest. This case reinforces the importance of early recognition of pulmonary mucormycosis and aggressive medical management, especially in immunocompromised patients, in salvaging lives with good outcomes and preventing the fulminant progression of the disease process., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sindhu et al.)

Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales.

Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat Candida albicans infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. Cmin (pre-dose) and Cmax (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (p = 0.03) between plasma and peritoneal Cmin. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC > 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections.

The stress response gene DDR48 has been characterized in Saccharomyces cerevisiae and Candida albicans to be involved in combating various cellular stressors, from oxidative agents to antifungal compounds. Surprisingly, the biological function of DDR48 has yet to be identified, though it is likely an important part of the stress response. To gain insight into its function, we characterized DDR48 in the dimorphic fungal pathogen Histoplasma capsulatum. Transcriptional analyses showed preferential expression of DDR48 in the mycelial phase. Induction of DDR48 in Histoplasma yeasts developed after treatment with various cellular stress compounds. We generated a ddr48∆ deletion mutant to further characterize DDR48 function. Loss of DDR48 alters the transcriptional profile of the oxidative stress response and membrane synthesis pathways. Treatment with ROS or antifungal compounds reduced survival of ddr48∆ yeasts compared to controls, consistent with an aberrant cellular stress response. In addition, we infected RAW 264.7 macrophages with DDR48-expressing and ddr48∆ yeasts and observed a 50% decrease in recovery of ddr48∆ yeasts compared to wild-type yeasts. Loss of DDR48 function results in numerous negative effects in Histoplasma yeasts, highlighting its role as a key player in the global sensing and response to cellular stress by fungi.

Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.

Deep mycosis of the scalp caused by Rhizopus oryzae mimicking kerion is rare. Herein, we report a case of such infection in a 5-year-old immunocompetent boy who presented with multiple painful boggy swellings with discharging sinuses on the scalp of 4 months' duration. Purulent discharge from the swelling cultured on Sabouraud's dextrose agar yielded R. oryzae species which was confirmed by molecular analysis by polymerase chain reaction. The child was managed with parenteral liposomal amphotericin-B which helped in clearance of infection.

Fixed cutaneous sporotrichosis (FCS) is a rare and chronic infection. Its diagnosis requires a high degree of suspicion. The data on its dermoscopy and follow-up is limited in the literature. We herein report one such case with a follow-up till cure along with its dermoscopy to establish certain specific features that may be used to ascertain the response to treatment for this chronic infection and its prognosis. We found only three such cases following an extensive review of the literature, and this case emphasizes the importance of dermoscopy in recent times as the history, swab cultures, and smears may be misleading at times due to the chronic and long-standing nature of the condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kothari et al.)

Background: Dermatophytosis is a major public health problem in our country. Although resistance to conventional oral and topical antifungal agents is being increasingly encountered, the sensitivity pattern of dermatophytes has not been systematically analysed.Aims: We aimed to determine the sensitivity pattern of dermatophyte isolates to amphotericin B and six oral antifungal drugs.Materials and Methods: Patients with dermatophytosis attending the outpatient department of dermatology were enrolled in the study. Samples were collected for mycological examination and in vitro antifungal sensitivity testing was done by broth microdilution as per the Clinical and Laboratory Standard Institute M38-A standards.Results: A total of 804 patients were enrolled. Specimens from 185 patients (23%) were both KOH and culture positive, and 44 of these isolates (41 Trichophyton mentagrophytes and 3 Trichophyton rubrum) were subjected to sensitivity testing. Minimum inhibitory concentrations (MIC) of itraconazole, ketoconazole, voriconazole and amphotericin B were comparable. The median MIC to fluconazole was higher than the other tested drugs. Dermatophytes were most susceptible to ketoconazole and voriconazole, followed by itraconazole, amphotericin B, fluconazole and griseofulvin. A high incidence of resistance was found to terbinafine and the difference was statistically significant in comparison to fluconazole, itraconazole, voriconazole, ketoconazole (P = 0.001) and griseofulvin (P = 0.003). The strains were more sensitive to amphotericin B as compared to griseofulvin (P = 0.02) and terbinafine (P < 0.001).Limitations: This was a hospital-based study and may not reflect the true pattern in the community. Only a few of the isolates were selected for study. The clinical response of patients, whose isolates were studied for in vitro sensitivity of the antifungals, was not studied.Conclusions: The sensitivity pattern of dermatophytes to various antifungals including amphotericin B, ketoconazole, voriconazole and itraconazole were determined. The studied isolates were least susceptible to terbinafine. [ABSTRACT FROM AUTHOR]

Background and Aim: Drug delivery through the microneedle array has been considered as an easy and noninvasive method in recent years. The purpose of this study was to design and construct an array of biodegradable polymeric microneedles containing Amphotericin-B to introduce this system and its use in the treatment of cutaneous lesions caused by Leishmania major parasite inoculation as a model in skin infections. Methods: In this study, microneedles were fabricated by three-step molding method, which included master mold making, polymeric matrix that blending of polyvinyl pyrrolidine and methacrylic acid and finally casting. Results: The identification of Amphotericin-B in polymeric microscopic compositions was investigated by absorption and emission spectroscopy. Also, the mechanical strength of microneedles, which confirms their ability to penetrate the skin, was investigated by a transducer. Conclusion: In this study, the design and fabrication of a skin-permeable polymeric microneedle array with biodegradability and biocompatibility characteristics in physiological environment was performed. Using the properties of designed needles, loading of Amphotericin-B was used for the treatment of leishmaniasis and skin fungal infections. [ABSTRACT FROM AUTHOR]

New formulations of Amphotericin-B (Am-B), the most popular therapeutic drug for many human infections such as parasitic and fungal pathogens, are safe, economical, and effective in the world. Several newly designed carrier systems for Am-B can also be considered orally with sufficient gastrointestinal permeability and good solubility. However, the clinical application of several new formulations of Am-B with organ cytotoxicity, low bioavailability, high costs, and technical problems have caused some issues. Therefore, more attention and scientific design are required to progress safe and effective drug delivery systems. Currently, the application of nano-based technology and nanomaterials in the advancement of drug delivery systems exhibits promising outcomes to cure many human systemic infections. Designing novel drug delivery systems including solid lipid nanostructured materials, lipo-polymersomes, drug conjugates and microneedles, liposomes, polymer and protein-based nanostructured materials, dendrimers, emulsions, mixed micelles, polymeric micelles, cyclodextrins, nanocapsules, and nanocochleate for Am-B has many advantages to reducing several related issues. The unique properties of nanostructured particles such as proper morphology, small size, surface coatings, and, electrical charge, permit scientists to design new nanocomposite materials against microorganisms for application in various human diseases. These features have made these nanoparticles an ideal candidate for drug delivery systems in clinical approaches to cure a number of human disorders and currently, several therapeutic nanostructured material formulations are under different stages of clinical tests. Hence, this scientific paper mainly discussed the advances in new formulations of Am-B for the treatment of human systemic infections and related clinical tests., (© 2023 Wiley-VCH GmbH.)

Polymannose (PM) having a weight-average molar mass (Mw) of 30-53 kDa was synthesized by the polycondensation of mannose using phosphorous acid as the catalyst and characterized by various techniques such as NMR, IR, GPC and polarimetry. 2D NMR results confirmed the presence of (1 → 6)-linked α-D-mannose residues as backbone with O-3 and O-2 substituted linear or branched chains in PM. Amphotericin B (AmB) was conjugated to periodate-oxidized PM through Schiff’s linkages at 20 wt% concentration. The AmB-PM conjugates were highly soluble in phosphate buffered saline (180-250 mg/mL), exhibited negligible hemolytic potential to human erythrocytes even at a concentration of 200 μg/mL (equivalent to ~40 μg/mL AmB) and were non-toxic to human embryonic kidney (HEK293T) cells even at a concentration of 250 μg/mL (equivalent to ~50 μg/mL AmB). The minimum inhibitory concentration of the AmB-PM conjugates against C. albicans, C. parapsilosis and C. neoformans was in the range of 0.5-1.0 μg/mL. Mannose receptors are widely expressed on myeloid cells such as macrophages, neutrophils, and dendritic cells. Therefore, apart from treating fungal infections, AmB-PM conjugates also may have therapeutic potential for the treatment of macrophage-associated diseases such as leishmaniasis where mannose receptors are overexpressed. [ABSTRACT FROM AUTHOR]

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−1 d−1; 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. [ABSTRACT FROM AUTHOR]

Background and Aims: Rhinocerebral mucormycosis is an aggressive fungal disease that involves the nose, par nasal sinuses, orbit and central nervous system. It may rapidly be fatal. The major route of infection is inhalation. This infection usually occurs secondary to immune suppression, diabetic ketoacidosis, and prolonged use of antibiotics, steroids, etc.Case report: We presented two cases of rhino cerebral mucormycosis with same presentation. Both patients had underlying disease (diabetes or immune deficiency). The symptoms began including colds and sinusitis and was accompanied by pain and swelling in face. Smear of necrotic tissue showed branching nonseptated mycelium in favor of mucosal. These patients were treated Included Medical therapy with amphotericin-B and surgical treatment was undertaken to drain the sinuses.Conclusions: The diagnosis of rhino cerebral mucormycosis should be considered in the hospital in diabetic patients. Early diagnosis and treatment, treatment of the underlying disease are crucial factors leading to a good outcome.*Corresponding author: Graduate of Nursing, Faculty Member of Neyshabur University of Medical Sciences, Khorasan razavi, Iran.Email: ali_kavosi1365@yahoo.com