Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Posaconazole is a lipophilic triazole antifungal agent that is structurally similar to itraconazole but has an expended spectrum of activity including yeast, molds, and dimorphic fungi. Posaconazole was licensed by the European Commission for the treatment of invasive aspergillosis, fusariosis, mycetoma, chromoblastomycosis, and coccidioidomycosis in adults who are refractory, or intolerant to other antifungal agents. Posaconazole was recently indicated for prophylaxis of invasive fungal infections in the following patients: patients receiving remission-induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose immunosuppressive therapy for versus host disease. The spectacular activity of posaconazole against refractory infections due to zygomycetes is encouraging and suggests using posaconazole in this case. Posaconazole is only available in oral suspension formulation. Posaconazole was well tolerated in clinical trials and has lower drug interaction profile compared to other available azoles.
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PMID:[The latest data on posaconazole]. 1726 54

We describe the clinical courses of 3 patients with hematologic malignancies (2 with acute myelogenous leukemia and 1 with multiple myeloma) who developed invasive fungal infections due to uncommon molds (Alternaria spp., Paecilomyces lilacinus, and Zygomycetes). Breakthrough invasive fungal infections of the sinus (n=1), lung (n=3), and pericardium (n=1) developed despite fluconazole prophylaxis and failed to respond to treatment with other licensed antifungal therapies, including amphotericin B (n=3), caspofungin (n=2), and voriconazole (n=3), and surgical intervention (n=2). Salvage therapy with posaconazole oral suspension resulted in successful outcomes in all 3 patients, who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) while on continued posaconazole therapy. The median duration of posaconazole treatment before HSCT was 5 months (range: 1.5-6 months). Posaconazole salvage therapy allowed successful allogeneic HSCT in 3 patients with refractory invasive mold infections.
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PMID:Posaconazole salvage therapy allows successful allogeneic hematopoietic stem cell transplantation in patients with refractory invasive mold infections. 1746 92

A neutropenic patient with acute myeloid leukaemia experienced a breakthrough infection of Trichosporon asahii during posaconazole treatment. After treatment was changed to a combination therapy with voriconazole and liposomal amphotericin B, the infection resolved. Posaconazole works effectively as an antifungal prophylaxis and salvage therapy in rare invasive fungal infections. This case however illustrates that breakthrough infections with T. asahii may occur during posaconazole treatment.
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PMID:Breakthrough infection of Trichosporon asahii during posaconazole treatment in a patient with acute myeloid leukaemia. 1769 Sep 28

Posaconazole is a second-generation triazole antifungal agent with a broad spectrum of activity that includes Aspergillus spp., Candida spp. and the Zygomycetes. In the US, posaconazole oral suspension administered three times daily is indicated for prophylaxis against invasive Aspergillus and Candida infections in patients aged > or =13 years who are at high risk of developing these infections because of immunosuppression, such as haematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or those with haematological malignancies with prolonged neutropenia as a result of chemotherapy. EU-approved prophylactic indications for posaconazole are similar to those in the US. Posaconazole provided effective prophylaxis against invasive fungal infections and was generally well tolerated in two large, well designed trials in HSCT recipients with GVHD, or patients receiving induction-remission chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) that was expected to result in prolonged neutropenia. It offers coverage of clinically relevant pathogens and is potentially associated with fewer drug-drug interactions than other licensed triazole antifungal agents. Its usefulness in some patients may be limited by the lack of an intravenous formulation, although one is currently being developed. As with other antifungal agents, concerns remain regarding the potential emergence of resistance to broad-spectrum antifungal prophylaxis with posaconazole. Despite this, posaconazole is a valuable emerging option for use as prophylaxis against invasive fungal infections in immunocompromized patients who are at high risk of developing these infections.
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PMID:Posaconazole : a review of its use in the prophylaxis of invasive fungal infections. 1845 64

Posaconazole (Noxafil (Schering-Plough Corporation) is a triazole antifungal approved in the United States for the treatment of oropharyngeal candidiasis and for the prophylaxis of Candida and Aspergillus infections in the immunocompromised host. Posaconazole is available only as an oral suspension. When used for the prevention of Candida and Aspergillus infections, posaconazole should be taken three times daily with a high fat meal to maximize oral absorption. Failure to take posaconazole with food will lead to subtherapeutic serum levels and decreased clinical effectiveness of the drug.We report the case of a 49-year-old woman with acute myeloid leukemia who received 4 months of posaconazole as an outpatient for the labeled indication of prophylaxis of Candida and Aspergillus infections. During her last admission, the patient presented with an invasive sinus infection diagnosed as a mixed Aspergillus and Mucor etiology. The patient succumbed to this infection five weeks after presentation. Upon investigation it was found that the patient did not self-administer posaconazole as required in the product labeling, which may have led to drug failure in this patient. We submit this case to illustrate the importance of patient education regarding proper administration of posaconazole. The important role of the outpatient physician, nurse, and pharmacist in this setting is underscored.
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PMID:Breakthrough invasive fungal infection in an immunocompromised host while on posaconazole prophylaxis: an omission in patient counseling and follow-up. 1875 83

Studies published during the past year on the treatment of several infectious diseases provide valuable information that should enable us to treat our patients more effectively. Among those findings: Oral vancomycin (Vancocin) is superior to oral metronidazole (Flagyl) for treating patients with severe Clostridium difficile-associated disease. The risk of death from any cause may be higher with the use of cefepime (Maxipime) than with other beta-lactam antibiotics. In patients presenting to primary care physicians with symptoms of acute maxillary sinusitis, antibiotics and topical nasal steroids do not seem to be effective, either alone or in combination. For patients with Bell palsy, early treatment with prednisolone improves the chance of complete recovery; antiviral therapy may be indicated for patients with complete facial nerve paralysis. In patients undergoing chemotherapy for acute myelogenous leukemia or myelodysplasia, posaconazole (Noxafil) prevented fungal infections more effectively than fluconazole (Diflucan) or itraconazole (Sporanox) and improved overall survival. Anidulafungin (Eraxis) was not inferior to fluconazole in the treatment of invasive candidiasis.
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PMID:Update in infectious disease treatment. 1875 40

There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).
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PMID:Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. 1906 34

The rising incidence of invasive fungal infections due to the expanding population of immunocompromised hosts and the increasing prevalence of fungal resistance has led to the need for novel antifungal agents. Posaconazole, a new member of the triazole class has demonstrated in vitro activity against a broad spectrum of fungi and clinical activity against various fungal pathogens, including Aspergillus spp., Candida spp., zygomycetes, and Fusarium spp. To date, posaconazole has been approved for prophylaxis of invasive fungal infections in stem cell transplant recipients with acute graft versus host disease (GVHD) and neutropenic patients receiving intensive induction chemotherapy for acute myelogenous leukemia and myelodys-plastic syndrome. In addition, it has been licensed for use in oropharyngeal candidiasis and for salvage therapy in invasive aspergillosis, fusariosis, coccidioidomycosis, chromoblastomycosis, and mycetoma. Posaconazole is the only azole with activity against zygomycetes and other difficult-to-treat fungi, representing a potential treatment option for refractory invasive mycosis. This article reviews available preclinical and clinical data of posaconazole, focusing on its role in the teatment of refractory invasive fungal infections.
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PMID:Posaconazole in the management of refractory invasive fungal infections. 1920 57

Owing to the morbidity and mortality associated with invasive fungal infections, particularly in the immunocompromised host, development of new agents for both prevention and treatment is essential. Posaconazole is a recently approved extended-spectrum triazole available as an oral suspension. It exhibits fungistatic activity against a variety of fungal pathogens. Pharmacokinetic data in special patient populations (such as neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome, allogeneic hematopoietic stem cell transplant recipients, febrile neutropenic patients and pediatric patients) have been published recently. Controlled clinical trials establish posaconazole's safety and efficacy in infections, such as oropharyngeal candidiasis and prophylaxis against invasive fungal infections. Data are also emerging in the treatment of zygomycosis and selected cases of aspergillosis. Posaconazole is well tolerated during short- and long-term use, with the most commonly reported adverse events being mild-to-moderate gastrointestinal disturbances. Data suggest a relationship between posaconazole plasma concentrations and prophylactic efficacy; however, the role of therapeutic drug monitoring has yet to be completely defined. Since posaconazole is available only as an oral formulation, its use may be limited in critically ill patient populations.
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PMID:Posaconazole's impact on prophylaxis and treatment of invasive fungal infections: an update. 1925 65

Posaconazole is a triazole with broad spectrum of activity against multiple fungi including members of the fungal order Mucorales. This activity has been shown both in clinical and in vitro studies, which are critically reviewed here. It has become very popular in prophylaxis in acute myelogenous leukemia (AML) induction and in the graft-versus-host disease (GVHD) settings after 2 recent prospective trials that showed advantage of posaconazole prophylaxis compared to fluconazole or itraconazole. In this report, 2 patients are presented, in whom, despite posaconazole prophylaxis, invasive and ultimately fatal Rhizopus pulmonary infections developed. These cases are similar to a previously reported case of Rhizopus infection in a stem cell transplant recipient who also received posaconazole, indicating a potential newly recognized pattern of breakthrough infections in patients receiving posaconazole prophylaxis.
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PMID:Fatal rhizopus pneumonia in allogeneic stem cell transplant patients despite posaconazole prophylaxis: two cases and review of the literature. 1958 89


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