amphotericin-b and Hypersensitivity

Bronchiectasis is a pathologic bronchial dilatation with loss of function that can result from multiple inflammatory and infectious injuries to the conducting airways of the lung. Molds, particularly the filamentous fungus Aspergillus fumigatus, have been implicated as a common cause of both cystic fibrosis (CF) and non-CF bronchiectasis, the latter primarily in patients with severe asthma. The pathogenesis of mold-associated bronchiectasis is usually due to atopic sensitization to mold allergens in the presence of active chronic endobronchial fungal infection with host innate and adaptive immune deviation to a Th2-dominated inflammation, a condition known as allergic bronchopulmonary aspergillosis (ABPA) (or allergic bronchopulmonary mycosis if a non-Aspergillus mold is implicated). Diagnostic criteria of ABPA continue to evolve, while treatment relies upon downregulation of the allergic inflammatory response with immunomodulatory agents and antifungal pharmacotherapy.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchiectasis; Cystic Fibrosis; Humans; Hypersensitivity; Immunoglobulin E; Triazoles

Compared to bacteria, the role of fungi within the intestinal microbiota is poorly understood. In this study we investigated whether the presence of a "healthy" fungal community in the gut is important for modulating immune function. Prolonged oral treatment of mice with antifungal drugs resulted in increased disease severity in acute and chronic models of colitis, and also exacerbated the development of allergic airway disease. Microbiota profiling revealed restructuring of fungal and bacterial communities. Specifically, representation of Candida spp. was reduced, while Aspergillus, Wallemia, and Epicoccum spp. were increased. Oral supplementation with a mixture of three fungi found to expand during antifungal treatment (Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi) was sufficient to recapitulate the exacerbating effects of antifungal drugs on allergic airway disease. Taken together, these results indicate that disruption of commensal fungal populations can influence local and peripheral immune responses and enhance relevant disease states.

Topics: Amphotericin B; Animals; Antifungal Agents; Bacteria; Base Sequence; Colitis; Dietary Supplements; Drug Hypersensitivity; Dysbiosis; Fluconazole; Fungi; Gastrointestinal Microbiome; Hypersensitivity; Intestines; Mice; Mice, Inbred C57BL

Hypersensitivity reactions to liposomal drugs, often observed with Doxil and AmBisome, can arise from activation of the complement (C) system by phospholipid bilayers. To understand the mechanism of this adverse immune reaction called C activation-related pseudoallergy (CARPA), we analyzed the relationship among liposome features, C activation in human serum in vitro, and liposome-induced cardiovascular distress in pigs, a model for human CARPA. Among the structural variables (surface charge, presence of saturated, unsaturated, and PEGylated phospholipids, and cisplatin vs. doxorubicin inside liposomes), high negative surface charge and the presence of doxorubicin were significant contributors to reactogenicity both in vitro and in vivo. Morphological analysis suggested that the effect of doxorubicin might be indirect, via distorting the sphericity of liposomes and, if leaked, causing aggregation. The parallelism among C activation, cardiopulmonary reactions in pigs, and high rate of hypersensitivity reactions to Doxil and AmBisome in humans strengthens the utility of the applied tests in predicting the risk of CARPA.. The authors studied complement activation-related pseudoallergy (CARPA) in a porcine model and demonstrate that high negative surface charge and drug effects leading to distortion of liposome sphericity might be the most critical factors leading to CARPA. The applied tests might be used to predict CARPA in humans.

Topics: Amphotericin B; Animals; Antibiotics, Antineoplastic; Complement Activation; Disease Models, Animal; Doxorubicin; Heart Arrest; Humans; Hypersensitivity; Liposomes; Phospholipids; Polyethylene Glycols; Surface Properties; Swine

The objective of this investigation was to explore the possibility of treating patients harboring invasive intracranial aspergillosis (InIA) at an early stage. Nineteen patients (age range 18-42 years) from a total of 114 cases of InIA seen from January 1999- December 2009 were included in this investigation. These individuals, all of whom had a past history of treated allergic fungal sinusitis (AFS) were evaluated as to their immune status, clinical presentations, time-intervals and radiological findings. Past records of seven patients indicated skull base erosion and extension of the paranasal (PNS) masses into intracranial cavity, but none had neurological deficits or symptoms suggestive of raised intracranial pressure. All 19 patients had undergone endoscopic clearance of PNS during their first presentations. Both AFS and InIA were found simultaneously in seven patients, while the time-interval between the two forms was as long as 10 years for two patients. Overall mortality was (8/19; 42%) with all deaths attributable to fungal meningo-encephalitis. As InIA carries a high mortality rate, it seems prudent to evaluate and treat these patients early in the course of their illness. The appearance of the invasive form of the disease in patients with a past history of AFS is not uncommon. The allergic form of disease may not be considered as a separate entity from InIA as both the pathologies may exist in same patient.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Cohort Studies; Encephalitis; Female; Humans; Hypersensitivity; Itraconazole; Male; Meningitis, Fungal; Sinusitis; Skull; Tomography, X-Ray Computed

Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome. The findings warrant future close supervision of patients to be treated with the drug.

Topics: Adult; Amphotericin B; Humans; Hypersensitivity; Leishmaniasis; Male; Middle Aged; Sudan

The role of fungi in chronic rhinosinusitis (CRS) is not clear. Fungi can be detected in the nose and paranasal sinuses of virtually all CRS patients; however, they also appear to be present in healthy controls. Various theories attempt to explain the mechanisms by which fungi can exert an effect on sinus mucosa in susceptible individuals. Further studies are necessary to clarify the role of fungi in CRS, which fungal organisms (if any) are pathogenic, and what exactly characterizes the immunologic response to fungi that may result in the development of disease. However, in the absence of convincing immunologic data and evidence of clinical improvement of CRS after antifungal therapy, the case against the fungus remains unproven.

Topics: Amphotericin B; Antifungal Agents; Antimicrobial Cationic Peptides; Chronic Disease; Cytokines; Fungi; Humans; Hyperplasia; Hypersensitivity; Immunotherapy; Mycoses; Pulmonary Surfactant-Associated Protein D; Sinusitis

We report a case of noninvasive pulmonary disease due to Chrysosporium zonatum in an immunocompetent male. The fungus colonized an existing tuberculous cavity and was isolated from transbronchial lavage fluid and from a percutaneous aspiration specimen. The disease was accompanied by the unusual feature of an allergic reaction. The fungus ball was successfully treated by intracavitary administration of amphotericin B. C. zonatum is the anamorph of the heterothallic ascomycete Uncinocarpus orissi, and the identity of the case isolate was verified by formation of ascospores in mating tests with reference isolates.

Topics: Aged; Amphotericin B; Chrysosporium; Humans; Hypersensitivity; Inflammation; Lung; Lung Diseases, Fungal; Male; Microbial Sensitivity Tests

Topics: Adult; Amphotericin B; Antibodies, Fungal; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Brain Abscess; Combined Modality Therapy; Humans; Hypersensitivity; Immunoglobulin A; Male; Sinusitis

Topics: Adult; Amphotericin B; Ethmoid Sinus; Female; Humans; Hypersensitivity; Middle Aged; Mycoses; Sinusitis

Topics: Amphotericin B; Antineoplastic Agents; Asparaginase; Endotoxins; Escherichia coli; Humans; Hypersensitivity; Interferons; Lipopolysaccharides; Neoplasms; Pyrogens

Dialyzable transfer factor, obtained from frozen-thawed peripheral blood leukocytes from a single donor, was given to five anergic patients with chronic mucocutaneous candidiasis. Studies of immunological responses including delayed cutaneous hypersensitivity, in vitro antigen-induced thymidine incorporation, and production of macrophage migration inhibition factor (MIF) were conducted both before and after injection of transfer factor. Before transfer factor, none of the patients had delayed skin responses to any of the natural antigens studied. Their lymphocytes did not produce MIF after exposure to antigens in vitro and only one patient showed increased thymidine incorporation when his lymphocytes were cultured with candida and streptokinase-streptodornase (SK-SD). After injection of transfer factor, four patients developed delayed skin responses to antigens to which the donor was sensitive; no recipient reacted to an antigen to which the donor was nonreactive. Lymphocytes from recipients produced MIF when cultured with antigens that evoked positive delayed skin tests. Only one patient developed antigen-induced lymphocyte transformation and this response occurred only intermittently. Attempts to sensitize three of the patients with the contact allergen, chlorodinitrobenzene, both before and after transfer factor, were unsuccessful. The fifth patient, a 9-yr old boy with an immunologic profile similar to the Nezelof syndrome, did not become skin test-reactive or develop positive responses to the in vitro tests. These findings suggest that transfer factor acts on the immunocompetent cells that respond to antigens with lymphokine production, but has little, if any, effect on cells that respond to antigens by blastogenesis. The failure to sensitize the subjects with chlorodinitrobenzene illustrates the specificity of the immunologic effects of transfer factor, and implies that it does not function through nonspecific, adjuvant-like mechanisms. Failure of transfer factor to produce positive skin tests or MIF production in a patient with Nezelof's syndrome may be evidence that lymphokine-producing cells are thymus derived.

Topics: Adult; Allergens; Amphotericin B; Antigens; Candidiasis, Cutaneous; Cell Migration Inhibition; Female; Humans; Hypersensitivity; Hypersensitivity, Delayed; Immunity, Cellular; Immunity, Maternally-Acquired; Immunologic Deficiency Syndromes; Leukocytes; Lymphocyte Activation; Lymphocytes; Macrophages; Male; Skin; Skin Tests; Thymidine

Topics: Adult; Amphotericin B; Antigens; Candida; Candidiasis; Chronic Disease; Female; Food Hypersensitivity; Humans; Hypersensitivity; Immunoglobulin E; Male; Nystatin; Saccharomyces; Skin Tests; Urticaria

Topics: Actinomycosis; Africa; Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Farmer's Lung; France; Histoplasmosis; Humans; Hypersensitivity; Lung Diseases, Fungal; Nystatin; Sputum; United States

Topics: Amphotericin B; Histoplasmosis; Humans; Hypersensitivity; Silicon Dioxide

Topics: Amphotericin B; Candida; Candida albicans; Candidiasis; Candidiasis, Cutaneous; Desensitization, Immunologic; Gentian Violet; Humans; Hypersensitivity; Nystatin