Influence of Potassium Ions on Act of Amphotericin B to the DPPC/Chol Mixed Monolayer at Different Surface Pressures

Amphotericin B (AmB) is an antifungal drug that rarely develops resistance. It has an affinity with the cholesterol on mammalian cell membranes, disrupting the structure and function of the membranes, which are also affected by potassium ions. However, the mechanism is unclear. In this paper, the Langmuir monolayer method was used to study the effects of potassium ions on the surface pressure–mean molecular area of isotherms, elastic modulus and the surface pressure–time curves of a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol (DPPC/Chol) monolayer and a DPPC/Chol/AmB monolayer. The morphology and thickness of the Langmuir–Blodgett films were studied via atomic force microscopy. The results showed that AmB can increase the mean molecular area of the DPPC/Chol mixed monolayer at low pressures (15 mN/m) but reduces it at high pressures (30 mN/m). The potassium ions may interfere with the effect of AmB in different ways. The potassium ions can enhance the influence of AmB on the stability of monolayer at low surface pressures, but weaken it at high surface pressures. The potassium ions showed significant interference with the interaction between AmB and the cholesterol-enriched region. The results are helpful for us to understand how the effect of amphotericin B on the phospholipid membrane is interfered with by potassium ions when amphotericin B enters mammalian cell membrane.

A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans

Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic.

Rhino Orbital Cerebral Mucormycosis in settings of Covid-19 infection: A Case Series of Thirteen Patients

Background Rhino-Orbital-Cerebral Mucormycosis (ROCM) is an important infectious disease encountered in huge number in this recent post-covid 19 era. An alteration in defence immune system during covid-19 illness, in the presence of uncontrolled hyperglycaemia has led to the new epidemic of ROCM especially in developing nations like India. Method This case series of thirteen patients illustrates the various clinical presentation, laboratorical parameters, imaging features and outcome of patients of ROCM admitted in a tertiary care hospital in Northern India. Result In our case series, a total of 13 newly diagnosed cases of Rhino-Orbital-Cerebral Mucormycosis were studied. History of covid-19 illness was observed in 7 cases (53.8%), use of steroid during Covid-19 illness was seen in 5 cases (38.5%), oxygen therapy was given in 4 cases (30.8%). Co-morbid state in the form of diabetes mellitus was present in 12 cases (92.3%) with mean duration 16.69 months with an important finding of 6 cases (46.2%) having new-onset diabetes; hypertension in present in 3 cases (23.1%). Magnetic resonance imaging of paranasal sinuses showed involvement of multiple sinuses in all the 13 cases(100%), including maxillary and ethmoidal sinuses, with frontal in 12 cases (92.3%), sphenoidal in 11 cases (84.6%), symmetric in 9 cases (69.2%), mastoiditis in 4 cases (30.8%), maxillary space involvement in 4 cases (30.8%), palatal involvement in 1 case (7.7%). Multi-speciality approach treatment was given in the liposomal amphotericin B therapy in all the patients along with thorough endo-nasal debridement done in all cases, transcutaneous retrobulbar amphotericin B in 6 cases (46.2%) with exenteration done in 7 patients (53.9%). At 3 months of follow-up, there was substantial clinical improvement in all the cases. Conclusion There should be definite emphasis on high suspicion of mucor clinically for early diagnosis and aggressive management at initial state of diagnosis for better outcome. The need for sustained proper glycemic control during covid 19 era along with judicious use of steroid and public awareness for early symptoms and manifestations of mucor can curb the magnitude of such potentially opportunistic epidemic to a substantial rate. The longer the infection remains undetected, the greater the devastation ROCM can impose, of which blindness is an important hazard.

Antifungal Resistance Trends of Candida auris Clinical Isolates, New York-New Jersey, 2016-2020

About 55% of U.S. Candida auris clinical cases were reported from New York and New Jersey from 2016 through 2020. Nearly all New York-New Jersey clinical isolates (99.8%) were fluconazole resistant, and 50% were amphotericin B resistant. Echinocandin resistance increased from 0% to 4% and pan-resistance increased from 0 to <1% for New York C. auris clinical isolates but not for New Jersey, highlighting the regional differences.

Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms

Purpose: Chronic infections of Candida albicans are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and Candida biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against Candida biofilms. Methods: AmB was encapsulated in the Molecular Envelope Technology (MET, N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan) nanoparticles and tested against Candida biofilms in vitro. Confocal laser scanning microscopy (CLSM) imaging of MET nanoparticles’ penetration into experimental biofilms was carried out and a MET-AmB eye drop formulation was tested for its stability. Results: MET-AmB formulations demonstrated superior activity towards C. albicans biofilms in vitro with the EC50 being ~30 times lower than AmB alone (EC50 MET-AmB = 1.176 μg mL−1, EC50 AmB alone = 29.09 μg mL−1). A similar superior activity was found for Candida glabrata biofilms, where the EC50 was ~10× lower than AmB alone (EC50 MET-AmB = 0.0253 μg mL−1, EC50 AmB alone = 0.289 μg mL−1). CLSM imaging revealed that MET nanoparticles penetrated through the C. albicans biofilm matrix and bound to fungal cells. The activity of MET-AmB was no different from the activity of AmB alone against C. albicans cells in suspension (MET-AmB MIC90 = 0.125 μg mL−1, AmB alone MIC90 = 0.250 μg mL−1). MET-AmB eye drops were stable at room temperature for at least 28 days. Conclusions: These biofilm activity findings raise the possibility that MET-loaded nanoparticles may be used to tackle Candida biofilm infections, such as refractory ocular fungal infections.

Comprehensive Analysis of Perioperative Anaesthesia Concerns in Covid Associated Mucormycosis: A Retrospective Study of Surgical Patients

Background: Data regarding sudden surge of mucormycosis cases with COVID-19 outbreak and its impact on anaesthesia management are lacking. This retrospective study was designed to analyze the number and characteristics of patients posted for mucormycosis surgery in COVID19 pandemic while emphasizing upon the anaesthesia concerns. Methods: Data was collected from all patients who were admitted with mucormycosis in our institute from the year 2020 onwards. Further analysis of patients who were surgically treated was carried out in terms of demographic characteristics, association with COVID19 and perioperative course of mucormycosis and anaesthetic management. All statistical analyses were performed with the Statistical package for social sciences (SPSS) version 25·0 software. Results: We report an incidence of 30 operated patients of the average age 52.60 years with mucormycosis from August 2020 to May 2021. Diabetes as a comorbidity was common (86.90%). Previous infection with COVID-19 was observed in 29 (96.60%) out of which 80% patients had residual pulmonary involvement. Concomitant medical therapy with Amphotericin B was received by 90% patients and subsequently 70% had deranged renal profile. While 20 % patients had compromised airway, 60 % required blood transfusion and 76.6% patients were electively ventilated while 1 patient (3.3%) succumbed amounting to a survival rate of 96.6%. Conclusion: To conclude elderly male diabetic patients with history of COVID19 infection is the most vulnerable population for developing mucormycosis. Airway management, glycemic control, concomitant Amphotericin B therapy and intraoperative bleeding are the major challenges for anaesthesiologist along with an element of post Covid respiratory compromise.

Phytocompounds of Bistorta macrophylla (D. Don) Sojak. as bioavailability enhancers of fluconazole and amphotericin B to better manage Candida species infections

Bistorta macrophylla (D. Don) Sojak. is a medicinal plant of high altitude and so far, not been scientifically explored? Since prehistoric times, B. macrophylla has been used to cure stomach pain, pyretic fever, flu, lungs infections, diarrhea, vomiting. The present research was aimed to examine the phytochemicals, antifungal, and synergistic potential of methanolic extracts of B. macrophylla. Methanolic extract of B. macrophylla was found to have high phenolic (191.18 ± 29.18 mg g−1 GAE) and flavonoid (26.71 ± 3.21 mg g−1 RE) content. Methanolic extract also demonstrate strong antifungal action with diameter of zone of inhibition of 17.5±0.5 mm (fungicidal) against both the strains of C. albicans (MTCC277 and ATCC90028). The minimal inhibitory concentration (MIC) of methanolic extract was found to be 62.5 µg ml−1 against C. albicans (MTCC277 and ATCC90028). In addition, the combination of methanolic extract of B. macrophylla with antifungal antibiotics (fluconazole and amphotericin B) showed synergistic interaction with MIC reduction from 4-128 folds against both candida strains. GC-MS analysis of methanolic extract revealed the presence of 15 major phytocompounds with area more than 1%. Molecular docking showed that sucrose and 9,9-Dimethoxybicyclo [ 3.3.1] nona-2,4-dione has highest binding energy of -6.3 and -5.1 KJ/mol against Cytochrome P450 14 alpha-sterol Demethylase (PDB ID: 1EA1) protein respectively. Combination of methanolic extract of B. macrophylla with antifungal antibiotics (fluconazole, amphotericin B) can be used to treat drug-resistant candida.