Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with acute leukaemia and malignant lymphomas often are severely affected by fungal infections. There is in particular growing concern about disseminated candidosis. Oral, gastrointestinal and systemic candidosis seem to be closely linked. Predisposing factors are damaged mucosal barriers due to chemotherapy, protracted periods of neutropenia, and prolonged use of antibiotics and steroids. Oropharyngeal candidosis is very frequent. This can be prevented or controlled by the application of topical antifungals such as nystatin. The systemic application of antifungals is an alternative for patients who do not respond. Both oral ketoconazole and intravenous amphotericin B have been proven effective. Candida oesophagitis is also an important problem. Oral nystatin suspension can be helpful in mild cases. In others oral ketoconazole and intravenous amphotericin B have to be used. A whole range of measures has to be taken to prevent spread of the disease, i.e. H2-antagonists should be used only if definitely needed. Specific antifungal prophylaxis has also been discussed. Oral amphotericin B seems to be helpful. The azole itraconazole might be especially promising.
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PMID:Oral and gastrointestinal candidosis: prophylaxis during immunosuppressive therapy. 270 Feb 21

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, < 500/microL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.
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PMID:Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome. 801 7

This report describes the clinical spectrum and outcome of the hemophagocytic syndrome (HS) in 5 HIV infected patients. All 5 patients presented with fever, hepatomegaly and/or splenomegaly, confusion or coma and respiratory symptoms. Severe anemia was associated with thrombocytopenia and with neutropenia in 4 cases. Diffuse intravascular coagulopathy was present in 2 cases. Liver function tests were abnormal in three patients. The diagnosis of HS was made 2 to 12 weeks after the onset of symptoms and required in most patients repeated examinations of the bone-marrow, showing infiltration by histiocytes with prominent phagocytosis of blood cells. In one case this infiltration was not seen in the bone-marrow but only in the liver and the spleen. Varicella, mycobacterium infection, oesophageal candidiasis, Kaposi sarcoma were observed in the evolution of 3 patients. Anaplastic large cell Ki-1 lymphoma was present in one case. Four patients died as a result of complications of HS. The one patient with lymphoma survived.
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PMID:[Hemophagocytic syndrome in HIV infection]. 824 41

Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in patients with AIDS or as treatment or primary prophylaxis in neutropenia associated with cancer therapy. Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal meningitis and AIDS. However, in this infection its efficacy as treatment relative to that of amphotericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction. In this regard, fluconazole has been proven superior to amphotericin B and to itraconazole 200 mg/day. Comparisons with other drugs used for the treatment of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effective as clotrimazole and ketoconazole; it was more so than the latter azole in 1 study. In patients undergoing chemotherapy or bone marrow transplantation, fluconazole as primary prophylaxis has produced greater clinical benefit than a clotrimazole regimen. The incidence of adverse events appears to be somewhat higher in patients with AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is similar. The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be clarified include: the use of fluconazole in children with AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; whether the drug influences mortality, as has been suggested by one placebo-controlled trial in patients undergoing bone marrow transplant; and the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of secondary resistance. Notwithstanding these undefined aspects of its clinical profile, fluconazole is now confirmed as an important antifungal drug in the management of fungal infections in patients with immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and is a preferred agent for secondary prophylaxis against candidal infections; it is also a favoured agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marrow transplantation .
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PMID:Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients. 853 53

Systemic non-Hodgkin's lymphoma and Kaposi's sarcoma occur in approximately 4% and 30% of patients with HIV infection, respectively. Single-agent or combination chemotherapy is often indicated for such patients. Combination chemotherapy produces a significant decrease in CD4 lymphocytes and significantly increases the risk of opportunistic infection. Supportive care should include prophylaxis against Pneumocystis carinii pneumonia and esophageal candidiasis. Herpes labialis frequently occurs, may be confused with chemotherapy-induced stomatitis, and it requires appropriate treatment and secondary prophylaxis once recognized. Antiretroviral therapy should be continued during chemotherapy, if possible, and should be selected based on the patient's prior antiretroviral exposure, the toxicity profile of the antiretroviral agent, the toxicity of the chemotherapy, and the potential for drug interaction. The use of hematopoietic growth factors as primary prophylaxis may be reasonable for patients at high risk for febrile neutropenia, although the information about their use in this population is limited.
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PMID:Infection prophylaxis and antiretroviral therapy in patients with HIV infection and malignancy. 891 6

Candida oesophagitis is a common concomitant disease in neutropenic cancer patients after chemotherapie as well as in HIV-patients. In order to characterize the features of oesophagitis in each population, we reviewed the medical history and pathology records of 23 patients (18 cancer-patients, 5 HIV-patients) with culture and autopsy-proven Candida oesophagitis. Histopathological patterns of morphology, invasion, angioinvasion and inflammation were evaluated. Virtually all patients, 17/18 cancer- and 5/5 HIV-patients, had a history of previous mucosal candidosis or candidemia. There was a significant difference histopathologically in depth of invasion of the Candida-organisms between cancer and HIV-patients. Only in HIV-patients organisms were observed within the muscularis propria and the adventitia (2/5 vs 0/18; p = 0.04). The frequency of angioinvasion (12/18 vs 3/5) was similar in both groups. Neutropenia (< 500/microliter) was present in 12 (68%) of 18 cancer patients vs 0/5 HIV-patients (p = 0.01). Correspondingly there was a significant higher PMN/MN ratio in the oesophageal inflammatory infiltrate in HIV-patients, reflecting chemotherapy-induced neutropenia in cancer patients (p = 0.02). Oesophageal candidosis in HIV-patients may be highly invasive despite the presence of neutrophils. These findings suggest an impaired inflammatory response of HIV-patients to invasive candidosis, leading to impaired mucosal host defence.
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PMID:[Patterns of Candida esophagitis in cancer and AIDS patients: histopathological study of 23 patients]. 941 19

Invasive esophageal candidiasis produced transmural necrosis leading to perforation in 2 patients aged 10 and 27 years. Both patients survived after esophageal resection and complete diversion. One patient with acute leukemia and neutropenia experienced systemic candidiasis, which resolved after esophagectomy. Esophagectomy and diversion for yeast-induced necrosis may lead to complete recovery and resolution of disseminated candidiasis when combined with systemic antifungal therapy.
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PMID:Surgical management of necrotizing Candida esophagitis. 1008 57

The epidemiological features of 37 episodes of candidemia in HIV-infected subjects were analysed in a retrospective matched case-control study conducted over an 8-year period (1990-1997). Univariate analysis identified eight risk factors that were significantly associated with candidemia (P<0.05): i) use of central venous catheters; ii) administration of total parenteral nutrition; iii) previous antifungal therapy; iv) previous therapy with glycopeptides; v) presence of oral/ esophageal candidiasis; vi) concomitant bacterial infections; vii) neutropenia; and viii) concomitant AIDS dementia complex. Stepwise logistic regression analysis revealed that the only independent risk factor for developing candidemia was the use of central venous catheters (P = 0.0001). Candida albicans was the most frequently isolated pathogen, accounting for 18 (48%) episodes of candidemia, followed by Candida tropicalis (19%) and Candida glabrata (11%). The crude mortality rate was 62%. On univariate analysis concomitant opportunistic infections, presence of non-Candida albicans species of Candida and neutropenia were shown to be predictive of death. Multivariate analysis revealed that the presence of non-Candida albicans strains of Candida was the only significant factor associated with a worse prognosis (P = 0.001). In conclusion, candidemia appears to be more common in patients with advanced HIV disease. Of the factors which influenced the onset of candidemia, use of central venous catheters seemed to be the most important one.
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PMID:Candidemia in HIV-infected subjects. 1048 24

Caspofungin is the first approved agent from a new class of antifungals, the echinocandins. By targeting the fungal cell wall (as opposed to the fungal cell membrane), the echinocandins exhibit a unique mechanism of action relative to the other currently approved antifungal agents. Preclinical (in vitro and in vivo) studies have demonstrated activity for caspofungin against the most commonly encountered fungi in the hospital setting, namely Candida and Aspergillus species. Caspofungin is administered as a once-a-day, intravenous formulation. Notably, caspofungin is neither an inhibitor, inducer, nor metabolite of the cytochrome p450 system. To date, few drug-drug interactions have been seen for this echinocandin. A number of Phase II and III clinical studies in documented invasive candidiasis, esophageal candidiasis, and invasive aspergillosis have been completed and have demonstrated efficacy for caspofungin against all three diseases. In all studies, caspofungin manifested an excellent safety profile with few serious, drug-related adverse events or discontinuations due to drug-related adverse events. Isolated symptoms compatible with histamine release have been infrequently reported. In clinical studies, drug-related nephrotoxicity with caspofungin has been rare, and the incidence of liver transaminase elevations has been similar to the incidence seen with comparator agents. Results from a Phase III study as empirical therapy in patients with febrile neutropenia are anticipated in late 2003. Overall, caspofungin represents an important addition to the current antifungal armamentarium.
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PMID:Caspofungin: the first in a new class of antifungal agents. 1296 85

Echinocandins are a new class of antifungal agents with a novel mechanism of action (interference with fungal cell wall synthesis). Caspofungin (Cancidas), Caspofungin MSD) is the first echinocandin to be approved and is administered intravenously. Caspofungin 50 mg/day had similar efficacy to intravenous fluconazole 200 mg/day and was at least as effective as intravenous amphotericin B 0.5 mg/kg/day in patients with oesophageal candidiasis in two randomised, double-blind studies. A favourable combined clinical and endoscopic response occurred in 81% of caspofungin recipients versus 85% of fluconazole recipients and in 74% of caspofungin recipients versus 63% of amphotericin B recipients. A favourable combined response rate of approximate, equals 90% and approximate, equals 60% occurred in the stratum of patients with oesophageal candidiasis who received caspofungin or amphotericin B in a third randomised, double-blind study. Caspofungin (70 mg loading dose followed by 50 mg/day) had similar efficacy to intravenous amphotericin B (0.7-1.0 mg/kg/day in patients with neutropenia and 0.6-0.7 mg/kg/day in patients without neutropenia) in patients with invasive candidiasis in a double-blind, randomised trial. A favourable overall response occurred in 73.4% of caspofungin recipients and in 61.7% of amphotericin B recipients. In a noncomparative study, salvage therapy with caspofungin (70 mg loading dose followed by 50 mg/day) was effective in patients with invasive aspergillosis who were refractory to or did not tolerate standard antifungal therapy. A favourable response (complete plus partial response) occurred in 37 of 83 patients (45%). Caspofungin was generally well tolerated in clinical trials; it had similar tolerability to intravenous fluconazole and was better tolerated than intravenous amphotericin B. Significantly fewer caspofungin than amphotericin B recipients reported chills, fever, nausea or infusion-related adverse events. In conclusion, caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative trials, caspofungin had similar efficacy to fluconazole and was at least as effective as amphotericin B in oesophageal candidiasis and had similar efficacy to amphotericin B in invasive candidiasis. In addition, caspofungin had similar tolerability to fluconazole and was better tolerated than amphotericin B in these indications. Caspofungin was also effective in patients with invasive aspergillosis who were refractory to or intolerant of standard antifungal agents. Thus, caspofungin provides an alternative to triazoles or amphotericin B in oesophageal candidiasis and an alternative to amphotericin B in invasive candidiasis, as well as being an effective salvage therapy in invasive aspergillosis.
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PMID:Caspofungin: a review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis. 1449 60


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