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Query: UMLS:C0027947 (neutropenia)
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The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.
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PMID:Toxicity of amphotericin b in children with cancer. 46 22

With the increased number of immunocompromised patients there has been a concomitant increase in patient morbidity and mortality due to fungi. The etiologic microorganisms vary depending upon the type of immune dysfunction. Patients with malignancies and chemotherapy-induced neutropenia commonly are infected with Candida and Aspergillus. Other ubiquitous fungi such as Rhizopus, Fusarium, and Trichosporon are more frequently implicated as agents of disease in these patients. Patients with cell-mediated immune dysfunction such as acquired immune deficiency syndrome (AIDS) are susceptible to mucocutaneous candidiasis and pulmonary and disseminated cryptococcosis. Histoplasmosis and coccidioidomycosis have been particularly lethal infections in AIDS patients. Contributing factors such as broad-spectrum antibiotic use, intravenous catheterization, malnutrition, hyperalimentation, multiple surgical procedures and/or trauma, and steroids used either singly or in combination may also predispose patients to invasive fungal disease. Definitive diagnosis is often difficult to establish and usually requires invasive biopsy. Delay of culture results due to the time required to process specimens and to allow the fungus to grow also contributes to the poor results of therapy. Biopsy of skin lesions represents a useful technique for making a diagnosis. Recent advances in antifungal therapeutics promise to change the current approach to treatment for several of the mycoses. The availability of new oral azoles with spectra of activity that include aspergillosis and cryptococcosis, which currently require treatment with parenteral amphotericin B, may prove practical for prolonged oral therapy of otherwise lethal mycoses.
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PMID:Fungal infections in the immunocompromised host. 268 23

We report the cases of six patients with AIDS in whom reactive hemophagocytic syndrome (RHPS) secondary to disseminated histoplasmosis was diagnosed. RHPS was diagnosed by established criteria, including fever (duration of > or = 7 days, with peak temperatures of > 38.5 degrees C), unexplained thrombocytopenia with anemia and/or neutropenia, and bone marrow biopsy findings of hemophagocytic histiocytosis. Disseminated Histoplasma capsulatum infection was diagnosed on the basis of the results of cultures of the bone marrow sample. The serum lactate dehydrogenase (LDH) level was elevated (> 1,000 IU/L) in all patients, and five of six patients had hyperferritinemia (range of ferritin level, 15,848-425,984 ng/mL). Five patients had features resembling severe sepsis with multiorgan dysfunction. Three patients recovered, and the findings of RHPS resolved following therapy with amphotericin B. In patients with AIDS, the combination of fever, cytopenia, elevated serum LDH level (> 1,000 IU/L), and/or hyperferritinemia (ferritin level of > 10,000 ng/mL) is a clue to the diagnosis of RHPS and disseminated histoplasmosis; bone marrow biopsy is valuable in establishing the diagnosis.
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PMID:Reactive hemophagocytic syndrome: a new presentation of disseminated histoplasmosis in patients with AIDS. 874 33

Fungal diseases are increasing among patients infected with human immunodeficiency virus (HIV) type 1. Infections due to Candida and Cryptococcus are the most common. Although mucocutaneous candidiasis can be treated with oral antifungal agents, increasing evidence suggests that prolonged use of these drugs results in both clinical and microbiologic resistance. The optimal therapy for cryptococcal meningitis remains unresolved, although initial treatment with amphotericin B, followed by life-long maintenance therapy with fluconazole, appears promising. Most cases of histoplasmosis, coccidioidomycosis, and blastomycosis occur in regions where their causative organisms are endemic, and increasing data suggest that a significant proportion of disease is due to recent infection. Aspergillosis is increasing dramatically as an opportunistic infection in HIV-infected patients, in part because of the increased incidence of neutropenia and corticosteroid use in these patients. Infection due to Penicillium marneffei is a rapidly growing problem among HIV-infected patients living in Southeast Asia. Although the advent of oral azole antifungal drugs has made primary prophylaxis against fungal diseases in HIV-infected patients feasible, many questions remain to be answered before the preventive use of antifungal drugs can be advocated.
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PMID:Emerging disease issues and fungal pathogens associated with HIV infection. 890 10

Infections of the nervous system remain a significant source of morbidity and mortality in patients with cancer. This paper reviews the main pathogens and emphasizes some of the principles of diagnosis and management of nervous system infections in cancer patients. Due to immunosuppression, diagnosis is more difficult in this group, secondary to the multitude of potential pathogens, and often by their atypical presentations. Fever or headache are often the only symptoms. Clinical history and general examination should guide appropriate studies such as neuroimaging. CSF analysis, cultures, and brain biopsy. Diagnostic evaluation should be pursued rapidly and aggressively since specific treatments can often reduce morbidity and mortality. Bacterial infections are generally due to break-down of the natural barriers and neutropenia. In neutropenia, Pseudomonas aeruginosa, and Enterobacteriae are the most frequent etiology. If all causes of immunodepression are included, Listeria monocytogenes meningitis is the main bacterial infection encountered. Fungal infections have emerged as a major cause of death among cancer patients. The prognosis of cryptococcosis and histoplasmosis meningitis are markedly improved with new antifungal therapy. Aspergillosis and Mucormycosis, which may cause cerebral abcesses and secondary vascular complications, are almost always fatal. The incidence of meningo-cerebral Candidiasis is often underestimated. Similar to Histoplasmosis, it is frequently disseminated. Viral infections are mainly seen in patients with T-lymphocyte defects. Herpes-simplex virus and Varicella-Zoster virus encephalitis should quicky lead to intravenous treatment with Acyclovir. As in AIDS patients, cerebral toxoplasmosis is the most frequent parasitic infection and appropriate therapy greatly reduces morbidity. It should be emphasized that multitude pathogens are often seen in cancer patients. Despite development of new therapeutic agents, central nervous system infections should still be considered life-threatening. Therefore, antibacterial, antifungal, and antiviral prophylaxis should be the rule for all cancer patients.
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PMID:[Central nervous system infections in patients with malignant diseases]. 903 51

Non-culture methods being developed and evaluated for mycotic infections include polymerase chain reaction (PCR), galactomannan (GM) antigenemia, Western blot (WB) to detect antibodies, and detection of the fungal metabolites D-arabinitol and (1,3)-beta-D-glucan. Sample preparation for PCR from blood specimens depends on fractionation of peripheral blood, its pre-incubation in blood culture broth, or a total DNA method, which does not rely on fractionation, or pre-incubation. Targets for PCR of fungi in the 18S or ITS2 subunits of the ribosomal RNA genes facilitated the design of Aspergillus and Candida genus and species probes. Amplicons were identified using PCR-enzyme linked immunosorbent assay (ELISA) or reverse line-blot formats. A pilot study indicated that PCR tests on blood specimens were positive at least once in patients with confirmed invasive aspergillosis (IA). When serum-PCR and serum-GM tests were compared in IA patients, antigenemia was more often positive. PCR detected Aspergillus DNA in bronchoalveolar lavage specimens from patients at risk even when cultures were negative. D-Arabinitol can be detected as a marker of candidiasis with gas chromatography-mass spectrometry or enzyme dependent-fluorometry. Each method can differentiate the microbial D- and host L-enantiomers. (1,3)-beta-D-Glucan is produced by most genera of pathogenic fungi and can be detected in plasma by the 'G-test'. In patients with febrile neutropenia the efficacy of azole therapy correlated with plasma (1,3)-beta-D-glucan concentrations of > or = 10 pg ml(-1). The diagnosis of early acute pulmonary histoplasmosis can be improved by a WB test utilizing deglycosylated M antigen, a 94-kDa glycoprotein. The identity of M antigen as a catalase was deduced from the sequence of the cloned gene. PCR identification of Histoplasma capsulatum cultures was accomplished with primer pairs selected from H and M antigen gene sequences.
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PMID:Non-culture based diagnostic tests for mycotic infections. 1120 40

Case records of 232 dogs and 29 cats with neutropenia were reviewed to examine the spectrum of underlying etiologies causing the neutropenia. Six etiological categories included nonbacterial infectious disease; increased demand due to marked inflammation, bacterial sepsis, or endotoxemia; drug-associated neutropenia; primary bone-marrow disease; immune-mediated neutropenia; and diseases of unclear etiology. The largest single category associated with the development of neutropenia was nonbacterial infectious disease (e.g., feline leukemia virus [FeLV], feline immunodeficiency virus [FIV], histoplasmosis, cryptococcosis, and parvovirus), with parvovirus infection accounting for 47.1% of all cases. The least common (0.38%) cause was naturally occurring immune-mediated neutropenia.
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PMID:Neutropenia in dogs and cats: a retrospective study of 261 cases. 1130 May 19

A 35-year-old man from Central America with a history of AIDS and numerous opportunistic infections presented with progressive neutropenia and thrombocytopenia despite having been stable for a period of 6 months. Cessation of antiviral medications did not stop his neutropenia, nor did use of folinic acid, G-CSF, or erythropoietin. The failure of these measures required repeated blood transfusions. Although the physical examination was relatively unremarkable, hematology and blood chemistries indicated that the patient needed urgent hospitalization due to fever and neutropenia. Neutropenia within HIV infection can be confusing, since it may be a result of the infection itself, an adverse effect of drug therapy, or from an opportunistic infection or malignancy. If the cause is not evident, it is wise to seek the etiology first rather than immediately use bone marrow stimulants, such as G-CSF. In this case, an infectious disease specialist made a diagnosis of disseminated histoplasmosis, after which the patient was treated with amphotericin B and released on itraconazole maintenance therapy.
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PMID:Profound neutropenia in an HIV-infected man. 1136 15

Respiratory and systemic mycoses are globally emerging as a problem of increasing importance in infectious diseases. This is attributed to the growing population of immunocompromised patients due to epidemic outbreak of AIDS or to other factors such as use of immunosuppressive drugs in recipients of organ transplantation. The available evidence has unequivocally established the endemic occurrence of blastomycosis, histoplasmosis and penicilliosis mameffei in India. In fact, pencilliosis marneffei has emerged as a major endemic mycosis of AIDS patients in Southeast Asia. It has manifestations simulating those of histoplasmosis capsulati, and it may spread to other regions with enlarging population of AIDS patients. Comprehensive studies are indicated in order to delineate the endemic areas of the afore-mentioned systemic mycoses. Among the other important systemic mycoses reported from India are aspergillosis, cryptococcosis, candidiasis and zygomycosis. Our current knowledge of the global distribution of systemic mycoses does not depict their true prevalence. It largely reflects the geographic distribution of medical mycologists or other investigators engaged in the study of fungal diseases and their research interests. Invasive aspergillosis has emerged as an important disease in patients with neutropenia and bone narrow transplant recipients, cryptoccosis, penicilliosis marneffei and pneumocystosis in patients with AIDS, fusariosis in patients with leukaemia receiving cytotoxic therapy, zygomycosis in diabetic patients and in patients on defroxamine therapy, and Malasseziafurfur infection in patients on total parenteral nutrition: Opportunistic systemic mycoses due to yeasts and yeast-like fungi have become commoner than those due to filamentous fungi, occupying fourth position in the list of bloodstream pathogens in some centers in USA. Also, their incidence, pattern of clinical presentations and species spectrum have significantly changed, largely due to more frequent and prolonged therapeutic or prophylactic use of antifungal drugs and subsequent development of resistance. Consequently, infections with resistant yeast-like fungi such as C. lusitaniae, C. krusei, C. tropicalis, C. glabrata and Trichosporon ovoides (T. beigelii) have recently been reported with greater frequency. Since respiratory and systemic mycoses have no pathognomonic clinical or radiologic syndrome and mycological diagnostic facilities are restricted to only some of the major metropolitan centres, these diseases may be frequently confused with tuberculosis or other diseases of obscure etiology in India and other developing countries. Greater awareness and a high index of clinical suspicion are important pre-requisites for their diagnosis. Also, active collaboration of internists, pathologists, mycologists and microbiologists is advocated for their expeditous diagnosis and successful management. Further studies should focus on the development of rapid techniques for selective isolation and identification of systemic pathogenic fungi. The problem of antifungal resistance is likely to become more serious in the future as more and more patients with AIDS, bone marrow transplantation and neutropenia will require chemoprophylaxis cover against systemic fungal infections. Thus, it would be of vital importance to intensify search for more potent and less toxic antifungal drugs. It is recognized that an increasing number of people whose life is saved or prolonged due to successful treatment of their underlying diseases fall victim to opportunistic, life threatening systemic mycoses. A great majority of the deaths due to these infections occurs because they remain undiagnosed for want of mycological diagnostic services. In order to cope with the challenge of systemic mycoses, the health authorities of the developing countries are called upon to urgently take necessary measures for establishing a network of diagnostic mycology laboratories.
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PMID:Respiratory and systemic mycoses: an overview. 1559 67

Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit (primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase II study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for >or=1 year.
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PMID:Posaconazole. 1603 92


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