amphotericin-b and Drug-Hypersensitivity

Triazole antifungal drugs may rarely cause serious allergic reactions including angioedema. No standardized tests are available to predict cross-reactivity within the azole class and little guiding information exists on whether to change therapy within the class or to another class after a serious allergic reaction. Herein we report the first successful use, to our knowledge, of graded isavuconazole introduction for treatment of aspergillosis in a liver transplant recipient with severe voriconazole allergy.

Topics: Amphotericin B; Angioedema; Antifungal Agents; Aspergillus; Desensitization, Immunologic; Drug Administration Schedule; Drug Hypersensitivity; Female; Humans; Liver Cirrhosis; Liver Transplantation; Lung; Middle Aged; Nitriles; Pulmonary Aspergillosis; Pyridines; Tomography, X-Ray Computed; Treatment Outcome; Triazoles; Voriconazole

Various adverse effects have been reported with the use of amphotericin B. The respiratory adverse effects include dyspnea, tachypnea, bronchospasm, hemoptysis, and hypoxemia. Stridor has not been previously reported with the use of amphotericin B.. To review the mechanism of action and reports of respiratory adverse effects for amphotericin B, the liposomal preparations of amphotericin B, and the differential diagnosis of stridor.. A MEDLINE search from 1966 to 2002 was performed to review the current literature for possible mechanisms and immunoregulatory effects related to the infusion of amphotericin B.. Amphotericin B has been shown to increase tumor necrosis factor alpha (TNF-alpha) concentrations in macrophages. In addition, it induces prostaglandin E2 synthesis and increases the production of interleukin 1beta (IL-1beta) in mononuclear cells. The immunoregulatory effects of amphotericin B include increases in apoptosis, production of monocyte chemoattractant protein 1, superoxide anion, nitric oxide, and intercellular adhesion molecule 1 expression.. Amphotericin B induces the production of TNF-alpha, interferon-gamma, and IL-1beta, which may potentiate its toxic effects. Some liposomal preparations induced lower levels of TNF-alpha and nitric oxide and may be useful in patients unable to tolerate amphotericin B deoxycholate.

Topics: Acute Disease; Aged; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Drug Compounding; Drug Hypersensitivity; Humans; Leukemia, Myeloid; Male; Respiratory Hypersensitivity; Respiratory Sounds

Horton giant cell arteritis can present with an atypical clinical picture that often resembles other diseases. In the case described below, the patient initially demonstrated clinical and laboratory evidence of a Candida albicans sepsis, and therefore we started antimycotic treatment with amphotericin B. Because of an adverse reaction to that drug, we added parenteral steroids before every administration of the antimycotic which led to an unexpected improvement of symptoms. This result caused us to reconsider some clinical aspects that could have been interpreted also as vasculitis, in particular for a giant cell arteritis: throbbing temporal headache, diffuse weakness, important rise in ESR, myoarthralgias. We performed a biopsy of the temporal artery that confirmed our diagnosis.

Topics: Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Biopsy; Candidiasis; Drug Hypersensitivity; Drug Therapy, Combination; Giant Cell Arteritis; Humans; Hydrocortisone; Male; Middle Aged; Prednisone; Recurrence; Temporal Arteries

Topics: Amphotericin B; Animals; Antifungal Agents; Antitubercular Agents; Crystallization; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Interactions; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Solubility; Sulfonamides

Topics: Amphotericin B; Analgesics; Anesthetics; Anti-Bacterial Agents; Bacitracin; Cephaloridine; Cephalothin; Drug Hypersensitivity; Humans; Kidney Diseases; Penicillins; Polymyxins; Sulfonamides; Tetracycline

Topics: Adult; Amphotericin B; Animals; Anti-Bacterial Agents; Bacitracin; Cats; Cycloserine; Drug Antagonism; Drug Hypersensitivity; Female; Hearing Disorders; Humans; Intestinal Diseases; Kidney Diseases; Liver Diseases; Male; Mental Disorders; Middle Aged; Neomycin; Novobiocin; Polymyxins; Stomach Diseases; Vision Disorders

The authors had for aim to define the threshold of nephrotoxicity before switching to other antifungal treatment in hematological patients treated by conventional amphotericin B (AmB) as an empiric antifungal treatment.. A prospective randomised multicenter study was made on 32 neutropenic hematological patients receiving conventional AmB for empirical antifungal treatment. The patients were randomised after a greater than or equal to 30% increase of serum creatinine (sCr). Patients in the early-switch group received liposomal AmB just after randomisation and patients in the late-switch group received liposomal AmB only when serum creatinine increase was greater or equal to 100% or sCr reached 170mumol/L.. Thirty-one patients were analysed: 16 patients in the early-switch group and 15 patients in the late-switch group (seven switched to liposomal AmB and eight continued conventional AmB treatment). The mean age of patients was 48 years and 68% were men. The most frequent underlying haematological malignancy was acute leukemia (94%). In the late-switch group, the degradation of renal function continued after randomisation contrary to the early-switch group: median variations of calculated sCr clearance in early- and late-switch groups were -16.8 and -1.5%, respectively (P=0.03). Moreover, an early switch was cost-effective with a sCr lower duration of hospitalisation in comparison with a late switch.. This randomised trial suggests that an early switch to Liposomal AmB improves and preserves renal function in comparison with a late switch.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Creatinine; Drug Hypersensitivity; Female; Humans; Kidney; Kidney Function Tests; Liposomes; Male; Middle Aged; Mycoses

Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play a central role in the treatment of bronchial asthma. Fluticasone exhibits excellent clinical effectiveness; however, oral adverse effects can occur.. To compare the frequency of oral candidiasis in asthmatic patients treated with fluticasone and beclomethasone, to evaluate the effect of gargling with amphotericin B, and to measure the inhalation flow rate on candidiasis.. The study consisted of 143 asthmatic patients who were treated with inhaled steroids, 11 asthmatic patients not treated with inhaled steroids, and 86 healthy volunteers. Quantitative fungal culture was performed by aseptically obtaining a retropharyngeal wall swab from these patients. Patients with positive results were treated with gargling using a 1:50 dilution amphotericin B solution. In asthmatic patients treated with fluticasone, the inhalation flow rate was measured using an inspiratory flow meter.. The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone. Gargling with amphotericin B was effective in most asthmatic patients with candidiasis. Candidiasis was not due to inappropriate flow rates during inhalation of steroids.. Fungal culture of a retropharyngeal wall swab may be useful for predicting the risk of developing oral candidiasis in asthmatic patients treated with inhaled steroids. The amount of isolated Candida was significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Attention to dosage is required as the amount of Candida increased with dose of fluticasone. Gargling with a 1:50 dilution of amphotericin B is effective in treating oral candidiasis of asthmatic patients treated with inhaled steroids.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Androstadienes; Anti-Inflammatory Agents; Antifungal Agents; Asthma; Beclomethasone; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Fluticasone; Glucocorticoids; Humans; Japan; Male; Middle Aged; Regression Analysis; Statistics as Topic; Treatment Failure

Invasive fungal infection is a problem in patients undergoing bone marrow transplantation (BMT). To determine if a liposomal formulation of amphotericin B (Ambisome) is safe and can prevent fungal infection we performed a placebo controlled double-blind randomized prophylactic trial. Study drug was administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was continued until neutrophils recovered to this level or an infection or toxicity end-point was reached. Thirty-six patients received 1 mg/kg/day of ambisome and 40 patients received placebo daily. There were no statistical differences in characteristics or clinical course between the two groups. Fungal colonization decreased in the ambisome group while it increased in the placebo group. By the end of prophylaxis 8 of 24 (33%) patients receiving ambisome were colonized compared with 18 of 29 (62%) placebo patients (p = 0.05). Five and 7 patients on ambisome or placebo, respectively, were withdrawn due to a presumed fungal infection (NS). There was no statistical reduction of autopsy-proven fungal infection. Proven fungal infection occurred in one patient receiving ambisome (C. guillermondi) compared with three patients receiving placebo (C. guillermondi, 2; C. albicans, 1). Ambisome was well tolerated at the dose of 1 mg/kg/day but in three patients allergic reactions were observed.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Double-Blind Method; Drug Carriers; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Immunocompromised Host; Infant; Liposomes; Male; Middle Aged; Mycoses; Safety

Intravenous administration of lipid-based nanodrugs can cause hypersensitivity, also known as infusion reactions (IRs), that can be attenuated by slow infusion in adult patients. We studied the role of infusion rate and complement (C) activation in IRs in pediatric patients treated with Abelcet, and also in anesthetized rats. IRs were observed in 6 out of 10 (60%) patients who received Abelcet infusion in 4 h or less, while no patients who received the infusion in 6 h showed C activation or IRs. The rat model indicated an inverse relationship between infusion speed and Abelcet-induced hypotension, taken as an experimental endpoint of IRs, while the rise of C3a in blood, an index of C activation, directly correlated with hypotension. The results suggest that pediatric patients are more prone to produce IRs, and that the optimal infusion time of Abelcet may be much longer than the presently recommended 2 h.

Topics: Amphotericin B; Animals; Antifungal Agents; Child; Complement Activation; Complement C3a; Drug Hypersensitivity; Humans; Infusions, Intravenous; Male; Rats; Rats, Wistar; Time Factors

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.. 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.. 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.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Australia; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Retrospective Studies; Young Adult

Complement activation-related pseudoallergy (CARPA) is an acute adverse immune reaction caused by many nanomedicines. There is a regulatory need for a sensitive and standardizable in vivo predictive assay. While domestic pigs are a sensitive animal model, miniature pigs are favored in toxicological studies yet their utility as a CARPA model has not yet been explored. Herein, we used liposomal doxorubicin and amphotericin B (Doxil/Caelyx and AmBisome), Cremophor EL and zymosan as CARPA triggers to induce reactions in miniature and domestic pigs, and compared the hemodynamic, hematological, biochemical, and skin alterations. The changes observed after administration of the test agents were very similar in both pig strains, suggesting that miniature pigs are a sensitive, reproducible, and, hence, validatable animal model for CARPA regulatory testing.. With the advances in nanomedicine research, many new agents are now tested for use in clinical setting. Nonetheless, complement activation-related pseudoallergy (CARPA) is a well known phenomenon which can be caused by nanoparticles. In this study, the authors looked at and compared the use of domestic pigs versus miniature pigs as experimental animals for toxicological studies. Their findings confirmed the possible use of miniature pigs for regulatory testing.

Topics: Amphotericin B; Animals; Complement Activation; Disease Models, Animal; Doxorubicin; Drug Hypersensitivity; Glycerol; Humans; Liposomes; Nanomedicine; Nanoparticles; Polyethylene Glycols; Swine; Swine, Miniature; Zymosan

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

Liposomal amphotericin-B (Ambisome(®)) is widely used antifungal drug for treatments of invasive fungal infections. The use of liposomal amphotericin-B is increasing in medical setting because of its tolerability and potent antifungal activity.. In a case of a 76 year-old Japanese female was admitted with subarachnoid hemorrhage, the ethnicity of the patient is Asian, we experienced that liposomal amphotericin-B was the culprit drug for Drug-induced hypersensitivity syndrome, also known as drug rash with eosinophilia and systemic symptoms in view of a clear temporal relationship between liposomal amphotericin-B administration and the onset of symptoms, the remission of the symptomatological pattern after liposomal amphotericin-B withdrawal.. The present case report shows that prolonged liposomal amphotericin-B treatment can be associated with drug rash with eosinophilia and systemic symptoms. We recommend careful monitoring of neutrophil counts in a prolonged treatment course with liposomal amphotericin-B.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Arm; Drug Hypersensitivity; Female; Humans; Syndrome

In spite of the development of new antifungal drugs, amphotericin B deoxycholate (d-AMB) remains the gold standard in the treatment of severe fungal infections in immunosuppressed hosts. However, d-AMB is a toxic drug, the most important dose-limiting toxicities being nephrotoxicity and infusion-related allergic reactions. Lipid and liposomal formulations of d-AMB have relatively lower toxicity and are considered alternative choices. However, the routine use of these formulations is limited by their higher cost. Using retrospective analysis, we explored the incidence of nephrotoxicity and allergic reactions requiring the cessation of conventional d-AMB in 113 cases treated with the drug. In contrast to knowledge in the relevant literature, we did not detect significant toxicity, which would have required discontinuation of the d-AMB treatment. Mean serum creatinine levels were 0.72 +/- 0.25 and 0.84 +/- 0.31 mg dl(-1) before and after therapy, respectively. Although the difference between creatinine levels before and after d-AMB is statistically significant, the creatinine level increased twofold in only eight cases. Mean serum potassium levels were 3.8 +/- 0.54 and 3.6 +/- 0.7 mmol l(-1) before and after d-AMB respectively. Potassium levels below 3 mmol l(-1) were found in 7 and 17 cases before and after d-AMB respectively. Potassium levels were statistically lower in cases with fungal mucositis. Severe infusion-related allergic reactions were observed in three cases. Antihistamine and corticosteroid were added to the treatment in these cases. With these findings, we can conclude that d-AMB is a tolerable, low cost drug which can be safely used provided there is suitable premedication and monitoring of blood urea nitrogen, serum potassium and magnesium levels.

Topics: Adolescent; Adult; Amphotericin B; Creatinine; Deoxycholic Acid; Drug Combinations; Drug Hypersensitivity; Female; Humans; Kidney; Magnesium; Male; Middle Aged; Mycoses; Neutropenia; Potassium; Retrospective Studies; Urea

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Brain Abscess; Caspofungin; Combined Modality Therapy; Contraindications; Craniotomy; Diabetes Complications; Diabetes Mellitus; Drug Hypersensitivity; Echinocandins; Female; Follow-Up Studies; Humans; Lipopeptides; Magnetic Resonance Imaging; Peptides; Peptides, Cyclic; Risk Assessment; Treatment Outcome

Topics: Aged; Amphotericin B; Antifungal Agents; Drug Hypersensitivity; Female; Humans; Male; Middle Aged

Topics: Amphotericin B; Drug Hypersensitivity; Humans; Infusions, Intravenous; Mycoses

Topics: Adult; Amphotericin B; Anaphylaxis; Candidiasis; Drug Hypersensitivity; Esophageal Diseases; Female; Humans; Liposomes; Male; Meningitis, Fungal

Topics: Adolescent; Adult; Aged; Amphotericin B; Bone Marrow Transplantation; Child; Child, Preschool; Drug Eruptions; Drug Hypersensitivity; Humans; Infant; Kidney Transplantation; Liposomes; Male; Middle Aged

Topics: Amphotericin B; Cephaloridine; Chemical Precipitation; Drug Combinations; Drug Hypersensitivity; Drug Incompatibility; Drug Stability; Humans; Hydrogen-Ion Concentration; Infusions, Parenteral; Protein Binding; Sulfadiazine; Tetracycline; Time Factors

Topics: Aged; Amphotericin B; Bronchial Spasm; Drug Hypersensitivity; Drug Tolerance; Humans; Male; Mucormycosis

Topics: Acute Disease; Amphotericin B; Drug Hypersensitivity; Histoplasmosis; Humans; Lung Diseases, Fungal

Topics: Acute Kidney Injury; Amphotericin B; Anti-Bacterial Agents; Bacitracin; Cephaloridine; Colistin; Drug Hypersensitivity; Gentamicins; Griseofulvin; Humans; Kanamycin; Kidney Function Tests; Methicillin; Penicillin G; Polymyxins; Streptomycin; Sulfonamides; Tetracycline

Topics: Amphotericin B; Anti-Bacterial Agents; Bacitracin; Chloramphenicol; Cross Infection; Drug Hypersensitivity; Drug Resistance; Drug Resistance, Microbial; Erythromycin; Kanamycin; Methicillin; Mycoses; Penicillins; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Toxicology; Vancomycin