Amphotericin B sodium cholesteryl sulfate complex 100mg powder for solution for infusion vials

Background: Voriconazole, isavuconazole, and amphotericin (AmB) formulations are currently recommended to treat invasive pulmonary aspergillosis (IPA). We aimed to estimate the efficacy of different antifungal drugs in the initial treatment of IPA. Methods: We included all available randomized controlled trials (RCTs) evaluating first-line treatments for IPA by searching PubMed, Medline, EMBASE, the Cochrane Library, and the ClinicalTrials.gov database. We performed a network meta-analysis to compare the relative efficacy of different drugs in treating IPA. The primary outcomes were the overall response and all-cause mortality (ACM). Results: Eight studies were identified that compared different drugs including voriconazole, isavuconazole, posaconazole, anidulafungin, liposomal AmB (L-AmB) at standard, high and low doses (3-5 mg/kg/d; 10 mg/kg/d; 1 mg/kg/d), AmB deoxycholate (dAmB) and amphotericin B colloidal dispersion (ABCD). We found that second-generation triazole antifungal drugs containing voriconazole, isavuconazole, and posaconazole exhibited significantly superior overall response to dAmB and ABCD. Voriconazole was ranked as the best drug on network rank analysis. We found no difference in efficacy between triazole antifungals and L-AmB. A combination of voriconazole with anidulafungin, isavuconazole and voriconazole showed significantly better safety than dAmB. Conclusion: The efficacy of second-generation triazole antifungal drugs for the first-line treatment of IPA is comparable with L-AmB and is better than both dAmB and ABCD. Isavuconazole may show better safety than voriconazole and posaconazole. Combination therapy with voriconazole and anidulafungin may serve as an alternative option for IPA patients with limited drug tolerance. Systematic review registration: https://inplasy.com/.

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We reported a 31-year-old man who received renal transplantation for more than 2 years. He was admitted to our hospital on 9 March 2022 due to intermittent diarrhea accompanied by leukopenia for more than 1 month. The patient successively developed high fever, cough, anemia, weight loss, gastrointestinal bleeding, and liver function impairment. Computed tomography (CT) revealed a slight inflammation in the lower lobes of both lungs, enlargement of the lymph nodes in the retroperitoneal and the root of mesenteric areas, and hepatosplenomegaly. Talaromyces marneffei was detected by metagenomics next-generation sequencing (mNGS) in blood and bronchoalveolar lavage fluid, and the pathogen was subsequently verified by blood culture. After endoscopic hemostatic therapy and antifungal therapy with voriconazole and amphotericin B cholesteryl sulfate complex, the patient was successfully discharged. Oral voriconazole was given regularly after discharge. Diarrhea, fever, enlargement of the lymph nodes, and endoscopic evidence of erosion may indicate intestinal T. marneffei infection. Although the mortality of T. marneffei infection after renal transplantation is very high, timely and effective antifungal therapy with amphotericin B cholesteryl sulfate complex is still expected to improve its prognosis.

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Mucormycosis is a rare opportunistic fungal infection associated with high mortality that typically occurs in immunocompromised patients. It is difficult to diagnose owing to non-specific clinical manifestations, the serologic index, imaging features, and the limitations of diagnostic methods. The incidence of invasive splenic mucormycosis is extremely rare, with only a few cases documented in the literature. We report a survival case of invasive splenic mucormycosis involving the liver caused by Rhizopus microsporus in a patient during consolidation therapy for acute monocytic leukemia (AML-M 5 ). The patient initially presented with recurrent fever and splenomegaly accompanied by multiple focal hypodensities unresponsive to empiric anti-infective treatment. Splenic mucormycosis was diagnosed by Contrast-Enhanced Ultrasonography (CEUS) and metagenomic next-generation sequencing (mNGS). However, surgical intervention carries a high risk due to the progressive involvement of the liver in invasive splenic mucormycosis. Fortunately, monotherapy with amphotericin B was effective, and the patient underwent allo-HSCT. This case aims to emphasize the importance of utilizing mNGS and CEUS for the timely diagnosis of mucormycosis to help clinicians identify splenic mucormycosis and initiate appropriate therapy as soon as possible to improve therapeutic efficacy and prognosis.

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Pulmonary mucormycosis (PM) is an invasive and life-threatening fungal infection that predominantly affects immunocompromised individuals. This study thoroughly examined the disease through three case reports and a literature review. Case 1 involved a patient with type 1 diabetes mellitus diagnosed through bronchoscopic histopathology, who succumbed despite a combination of oral isavuconazole, nebulized amphotericin B, and intravenous amphotericin B cholesteryl sulfate complex. Case 2 involved a patient with follicular non-Hodgkin lymphoma who had a concurrent coronavirus disease 2019 (COVID-19) infection, which was confirmed through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient experienced clinical improvement following sequential intravenous voriconazole, amphotericin B cholesteryl sulfate complex, and oral isavuconazole. Case 3 involved a patient diagnosed with mNGS in a lung cancer patient with chronic obstructive pulmonary disease, who showed poor therapeutic response to combined intravenous voriconazole, amphotericin B cholesteryl sulfate complex, and oral isavuconazole, resulting in fatal outcomes. Literature synthesis revealed mortality rates of 28.3% with antifungal monotherapy compared to 23.7% when antifungal monotherapy was combined with bronchoscopic intervention; the mortality rate for antifungal-surgical combination therapy was 9%. Notably, all 13 patients receiving multimodal treatment (antifungals, bronchoscopy, and surgery) survived. These findings underscore that combination therapy integrating pharmacotherapy, bronchoscopic intervention, and surgical resection demonstrated significantly superior survival outcomes compared to monotherapy.

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Liposomal amphotericin B (Ambisome®) is the gold standard for the treatment and prevention of fungal infections both in the adult and pediatric populations. The lyophilized dosage form has to be reconstituted and diluted by hospital staff, but its management can be challenging due to the spontaneous tendency of amphotericin B to form aggregates with different biological activity. In this study, the colloidal stability of the liposomes and the chemical stability of amphotericin B were investigated over time at storage conditions. Three liposomal formulations of amphotericin B at 4.0 mg/mL, 2.0 mg/mL, and 0.2 mg/mL were prepared and assayed for changes regarding the dimensional distribution, zeta potential, drug aggregation state, and onset of by-products. Our analyses highlighted that the most diluted formulation, kept at room temperature, showed the greatest changes in the aggregation state of the drug and accordingly the highest cytotoxicity. These findings are clinically relevant since the lower dosages are addressed to the more vulnerable patients. Therefore, the centralization of the dilution of AmBisome® at the pharmacy is of fundamental importance for assuring patient safety, and at the same time for reducing medication waste, as we demonstrated using the cost-saving analysis of drug expense per therapy carried out at the G. Gaslini children hospital.

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Plasticizers are employed to stabilize films by safeguarding their physical stability and avoiding the degradation of the loaded therapeutic drug during processing and storage. In the present study, the plasticizer effect (glycerol) was studied on bioadhesive films based on sodium alginate (SA), carboxymethyl cellulose (CMC) and gelatin (GE) polymers loaded with amphotericin B (AmB). The main objective of the current study was to assess the morphological, mechanical, thermal, optical, and barrier properties of the films as a function of glycerol (Gly) concentration (0.5-1.5 %) using different techniques such as Scanning Electron Microscope (SEM), Texture analyzer (TA), Differential Scanning Calorimeter (DSC), X-Ray Diffraction (XRD), and Fourier Transforms Infrared Spectroscopy (FTIR). The concentration increase of glycerol resulted in an increase in Water Vapor Permeability (WVP) (0.187-0.334), elongation at break (EAB) (0.88-35.48 %), thickness (0.032-0.065 mm) and moisture level (17.5-41.76 %) whereas opacity, tensile strength (TS) (16.81-0.86 MPa), and young's modulus (YM) (0.194-0.002 MPa) values decreased. Glycerol incorporation in the film-Forming solution decreased the brittleness and fragility of the films. Fourier Transform Infrared (FTIR) spectra showed that intermolecular hydrogen bonding occurred between glycerol and polymers in plasticized films compared to control films. Furthermore, molecular docking was applied to predict the binding interactions betweem AmB, CMC, gelatin, SA and glycerol, which further endorsed the stabilizing effects of glycerol in the complex formation between AmB, CMC, SA, and gelatin. The Findings of the current study demonstrated that this polymeric blend could be used to successfully prepare bioadhesive films with glycerol as a plasticizer.

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Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.

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BACKGROUND: Nanoparticles (NPs) have emerged as highly efficient drug delivery vehicles. NPs are characterised by their ability to safeguard drugs, enhance stability, prolong durability, and facilitate targeted tissue delivery. Moreover, NPs can be customised to either stimulate or suppress immune responses while evading immune detection. MAIN BODY: An increasing body of research demonstrated the therapeutic advantages of delivering various substances via surface-engineered NPs particularly in targeting immune cells. A broad spectrum of nanomaterials has been recognised for their superior ability to elicit immune responses, thereby enhancing disease prevention and therapeutic outcomes in vivo. In this comprehensive review, we discuss the impact of bioresponsive NPs on immunostimulation, immunomodulation, and immunosuppression. Particular focus is placed on how the physiochemical properties of these NPs influence the interaction between immune cells and host tissues, thereby achieving the desired immune regulation to combat various human diseases while reducing immunotoxicity. Additionally, we examined immune-inspired and immune-mediated strategies for the targeted delivery of NPs to specific sites within the body. Finally, we highlight the importance of understanding and focusing on immune cell trafficking mechanisms, as deeper insights into these processes may guide the rational design and fabrication of NPs capable of specifically targeting altered immune pathways under pathological conditions. This review offers an in-depth understanding of the diverse roles of bioresponsive NPs in immune regulation and targeted drug delivery, aiming to advance therapeutic strategies for a wide range of human diseases. CONCLUSION: Nanomaterials possess significant immunomodulatory capabilities, enhancing both disease prevention and therapeutic efficacy in vivo, yet their clinical translation is hindered by complex fabrication methods and high production costs. Future efforts must focus on simplifying synthesis and improving cost-efficiency to facilitate their adoption in clinical practice.

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