- Efficacy of nebulized liposomal amphotericin B in the treatment of ABPA in an HIV/HBV co-infected man: Case report and literature review. [Journal Article]
- JAJ Asthma 2018 Feb 16; :1-3
- Comparing the therapeutic efficacy of different amphotericin B-carrying delivery systems against visceral leishmaniasis. [Journal Article]
- EPExp Parasitol 2018 Feb 13; 186:24-35
- Amphotericin B (Amp) has been well-successfully used to treat against Leishmania infection, although high toxicity has been found in patients. In the present study, Amp was administered in Leishmania...
Amphotericin B (Amp) has been well-successfully used to treat against Leishmania infection, although high toxicity has been found in patients. In the present study, Amp was administered in Leishmania infantum-infected BALB/c mice by three distinct delivery systems aiming to compare their efficacy against challenge infection, as well as their side effects in a murine visceral leishmaniasis (VL) model. This product was administered in a Poloxamer P407 (Pluronic®F127)-based polymeric micelle system (Amp/M), in the Ambisome®formulation (Lip-Amp) or in a free format (free Amp). Glucantime®(Gluc) was used as a comparative drug. Aiming to evaluate different endpoints of the treatments, the efficacy of the compounds was investigated one and 15-days after the therapeutic regimens, determining the parasite load by a limiting dilution assay and a quantitative PCR (qPCR) technique, as well as evaluating the immune response generated in the infected and treated animals. In the results, Amp/M or Lip-Amp-treated mice presented the best outcomes, since significant parasite load reductions were found in the evaluated organs, as well as a parasite-specific Th1 immune response was observed in the animals. In addition, no hepatic or renal damage was found in these mice. On the other hand, free Amp or Gluc induced toxicity in the animals, which was associated with a low Th1 immune response. Comparatively, Amp/M was the most effective drug in our experimental model, and results showed that the Amp-carrying system could be considered as a future alternative in studies against VL.
- Successful Combination Therapy of Liposomal Amphotericin B and Caspofungin for Disseminated Fusariosis in a Pediatric Patient with Acute Lymphoblastic Leukemia. [Journal Article]
- PIPediatr Infect Dis J 2018 Feb 12
- Disseminated fusariosis is a fatal infection in immunocompromised hosts. However, the optimal antifungal treatment for disseminated fusariosis has not yet been established. We report a case of dissem...
Disseminated fusariosis is a fatal infection in immunocompromised hosts. However, the optimal antifungal treatment for disseminated fusariosis has not yet been established. We report a case of disseminated fusariosis after chemotherapy for acute lymphoblastic leukemia, presenting with multiple skin, lung, and kidney lesions and cerebrospinal fluid invasion. The combination therapy of liposomal amphotericin B and caspofungin resolved disseminated fusariosis successfully.
- The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles. [Journal Article]
- MBIOMBio 2018 Feb 06; 9(1)
- The fungal cell wall is a critically important structure that represents a permeability barrier and protective shield. We probedCandida albicansandCryptococcus neoformanswith liposomes containing amp...
The fungal cell wall is a critically important structure that represents a permeability barrier and protective shield. We probedCandida albicansandCryptococcus neoformanswith liposomes containing amphotericin B (AmBisome), with or without 15-nm colloidal gold particles. The liposomes have a diameter of 60 to 80 nm, and yet their mode of action requires them to penetrate the fungal cell wall to deliver amphotericin B to the cell membrane, where it binds to ergosterol. Surprisingly, using cryofixation techniques with electron microscopy, we observed that the liposomes remained intact during transit through the cell wall of both yeast species, even though the predicted porosity of the cell wall (pore size, ~5.8 nm) is theoretically too small to allow these liposomes to pass through intact.C. albicansmutants with altered cell wall thickness and composition were similar in both theirin vitroAmBisome susceptibility and the ability of liposomes to penetrate the cell wall. AmBisome exposed to ergosterol-deficientC. albicansfailed to penetrate beyond the mannoprotein-rich outer cell wall layer. Melanization ofC. neoformansand the absence of amphotericin B in the liposomes were also associated with a significant reduction in liposome penetration. Therefore, AmBisome can reach cell membranes intact, implying that fungal cell wall viscoelastic properties are permissive to vesicular structures. The fact that AmBisome can transit through chemically diverse cell wall matrices when these liposomes are larger than the theoretical cell wall porosity suggests that the wall is capable of rapid remodeling, which may also be the mechanism for release of extracellular vesicles.IMPORTANCEAmBisome is a broad-spectrum fungicidal antifungal agent in which the hydrophobic polyene antibiotic amphotericin B is packaged within a 60- to 80-nm liposome. The mode of action involves perturbation of the fungal cell membrane by selectively binding to ergosterol, thereby disrupting membrane function. We report that the AmBisome liposome transits through the cell walls of bothCandida albicansandCryptococcus neoformansintact, despite the fact that the liposome is larger than the theoretical cell wall porosity. This implies that the cell wall has deformable, viscoelastic properties that are permissive to transwall vesicular traffic. These observations help explain the low toxicity of AmBisome, which can deliver its payload directly to the cell membrane without unloading the polyene in the cell wall. In addition, these findings suggest that extracellular vesicles may also be able to pass through the cell wall to deliver soluble and membrane-bound effectors and other molecules to the extracellular space.
- A Young, Immunocompetent Woman with Small Bowel and Hepatic Mucormycosis Successfully Treated with Aggressive Surgical Debridements and Antifungal Therapy. [Journal Article]
- CRCase Rep Infect Dis 2017; 2017:4173246
- A 24-year-old woman with coeliac disease and transient neutropenia developed mucormycosis with extensive involvement of the liver and small intestine. She was successfully treated with aggressive sur...
A 24-year-old woman with coeliac disease and transient neutropenia developed mucormycosis with extensive involvement of the liver and small intestine. She was successfully treated with aggressive surgical debridements and long-term antifungal therapy with liposomal amphotericin B and posaconazole.
- Successful Treatment of Disseminated Cutaneous Leishmaniasis With Liposomal Amphotericin B and Miltefosine in an Eight-year-old Girl. [Journal Article]
- PIPediatr Infect Dis J 2018; 37(3):275-277
- This case report presents an 8-year-old girl, from Fars province in Iran, diagnosed with cutaneous leishmaniasis in the form of multiple nodular, ulcerative and crusted lesions disseminated on the fa...
This case report presents an 8-year-old girl, from Fars province in Iran, diagnosed with cutaneous leishmaniasis in the form of multiple nodular, ulcerative and crusted lesions disseminated on the face, trunk and extremities. The result of direct smear of ulcers was positive for Leishmania parasite. The patient had no immunodeficiency or relevant family history making her susceptible for disseminated cutaneous leishmaniasis. The skin lesions failed to respond to multiple treatment courses of meglumine antimoniate or amphotericin B but were successfully treated with simultaneous miltefosine and liposomal amphotericin B.
- Analysis of the in vitro activity of human neutrophils against Aspergillus fumigatus in presence of antifungal and immunosuppressive agents. [Journal Article]
- MMMed Mycol 2017 Oct 09
- Neutrophils are essential in the first line defense against moulds. This in vitro study assessed different neutrophil effector mechanisms in the presence of clinically relevant antifungal and immunos...
Neutrophils are essential in the first line defense against moulds. This in vitro study assessed different neutrophil effector mechanisms in the presence of clinically relevant antifungal and immunosuppressive agents. Therapeutic concentrations of liposomal amphotericin B led to reduced IL-8 and oxidative burst response to the synthetic stimulus PMA, whereas no major alterations of oxidative burst, phagocytosis, or cytokine response to germinated stages of Aspergillus fumigatus and no supra-additive effects of antifungal and immunosuppressive drugs were observed. Conventional and liposomal amphotericin B as well as voriconazole, however, led to reduced neutrophil extracellular trap formation in response to A. fumigatus germ tubes.
- The Aspergillus fumigatus Sialidase (Kdnase) Contributes to Cell Wall Integrity and Virulence in Amphotericin B-Treated Mice. [Journal Article]
- FMFront Microbiol 2017; 8:2706
- Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening invasive pulmonary aspergillosis (IPA) in immunocompromised individuals. We previously characterized an exo-sialidase f...
Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening invasive pulmonary aspergillosis (IPA) in immunocompromised individuals. We previously characterized an exo-sialidase from A. fumigatus that prefers the sialic acid substrate, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (Kdn); hence it is a Kdnase. Sialidases are known virulence factors in other pathogens; therefore, the goal of our study was to evaluate the importance of Kdnase in A. fumigatus. A kdnase knockout strain (Δkdnase) was unable to grow on medium containing Kdn and displayed reduced growth and abnormal morphology. Δkdnase was more sensitive than wild type to hyperosmotic conditions and the antifungal agent, amphotericin B. In contrast, Δkdnase had increased resistance to nikkomycin, Congo Red and Calcofluor White indicating activation of compensatory cell wall chitin deposition. Increased cell wall thickness and chitin content in Δkdnase were confirmed by electron and immunofluorescence microscopy. In a neutropenic mouse model of invasive aspergillosis, the Δkdnase strain had attenuated virulence and a significantly lower lung fungal burden but only in animals that received liposomal amphotericin B after spore exposure. Macrophage numbers were almost twofold higher in lung sections from mice that received the Δkdnase strain, possibly related to higher survival of macrophages that internalized the Δkdnase conidia. Thus, A. fumigatus Kdnase is important for fungal cell wall integrity and virulence, and because Kdnase is not present in the host, it may represent a potential target for the development of novel antifungal agents.
- Trypanosomiasis in a Young Infant from Rural Gujarat, India. [Journal Article]
- IPIndian Pediatr 2018 Jan 15; 55(1):69-70
- Human trypansomiasis due to infection by animal trypanosomes is rarely reported from India.
Human trypansomiasis due to infection by animal trypanosomes is rarely reported from India.
New Search Next
- Fulminant presentation of oral mucosal leishmaniasis as severe stomatitis and periodontitis. [Journal Article]
- NJNeth J Med 2018; 76(1):40-42
- This case report shows an atypical presentation of mucosal leishmaniasis infantum in the oral cavity resulting in severe stomatitis and periodontitis. The patient was immunocompromised because of rhe...
This case report shows an atypical presentation of mucosal leishmaniasis infantum in the oral cavity resulting in severe stomatitis and periodontitis. The patient was immunocompromised because of rheumatoid arthritis for which he used prednisone and methotrexate. He was treated with intravenous liposomal amphotericin B and recovered within four weeks.