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

Pulmonary aspergillosis is a severe complication in heart transplant recipients. The drug of choice for this infection is amphotericin B, but its use is limited because of its side effects. We observed six cases of pulmonary aspergillosis in a group of 200 patients who had received heart transplants from January 1988 to January 1999. Predisposing factors such as previous rejection, neutropenia and/or cytomegalovirus reactivation were present in all patients. The clinical presentation was characterized by fever and a non-productive cough. X-rays showed monolateral or diffuse infiltrate with or without nodular lesions. The median interval between symptoms and diagnosis was 5 d (range 4-7). Diagnosis was made by culturing trans-tracheal aspirate samples. Aspergillus fumigatus was isolated in 3 patients and A. niger in the other 3. All patients were treated with itraconazole at 200-400 mg/day for 20-60 d and all recovered. One patient treated with the lowest dosage for the shortest term had a recurrence after 1 month and needed a second 30-day course of itraconazole at a higher dosage. No significant side effects were registered. Itraconazole is effective in the therapy of pulmonary aspergillosis, particularly when an early diagnosis is made.
 ...
PMID:Improved outcome of pulmonary aspergillosis in heart transplant recipients with early diagnosis and itraconazole treatment. 1094 97

Fungal infections are a leading cause of mortality in patients with neutropenia. Candidiasis and aspergillosis account for most invasive fungal infections. General prophylactic measures include strict hygiene and environmental measures. Haemopoietic growth factors shorten the duration of neutropenia and thus may reduce the incidence of fungal infections. Fluconazole is appropriate for antifungal prophylaxis and should be offered to patients with prolonged neutropenia, such as high-risk patients with leukaemia undergoing remission induction or consolidation therapy and high-risk stem cell transplant recipients. Empirical antifungal therapy is mandatory in patients with persistent febrile neutropenia who fail to respond to broad-spectrum antibacterials. Intravenous amphotericin B at a daily dose of 0.6 to 1 mg/kg is preferred whenever aspergillosis cannot be ruled out. Lipid formulations of amphotericin B have demonstrated similar efficacy and are much better tolerated. Fluconazole is the best choice for acute candidiasis in stable patients; amphotericin B should be used in patients with unstable disease. Use of fluconazole is restricted by the existence of resistant strains (Candida krusei and, to a lesser extent, C. glabrata). Amphotericin B still remains the gold standard for invasive aspergillosis. Lipid formulations of amphotericin B are effective in aspergillosis and because they are less nephrotoxic are indicated in patients with poor renal function. Itraconazole is an alternative in patients who have good intestinal function and are able to eat. Mucormycosis, trichosporonosis, fusariosis and cryptococcosis are less common but require specific management. New antifungal agents, especially new azoles, are under development. Their broad in vitro spectrum and preliminary clinical results are promising.
 ...
PMID:Fungal infections in patients with neutropenia: challenges in prophylaxis and treatment. 1119 Apr 15

Among the serious complications associated with bone marrow transplantation are invasive fungal infections caused by organisms such as Candida and Aspergillus species and end-organ disease caused by cytomegalovirus (CMV). Successful prevention of these complications can have a significant impact on morbidity and mortality. The primary option for prophylaxis against fungal infections is fluconazole (Diflucan). Low doses of intravenous amphotericin B may be useful where there is a higher rate of aspergillosis. Itraconazole (Sporanox) and nasal amphotericin B are other options that have been less well studied. The development of fluconazole-resistant candidiasis may become problematic. Ganciclovir (Cytovene) is useful for the prevention of end-organ disease caused by CMV but carries a significant risk for neutropenia. New techniques for the early detection of CMV infection should allow prophylaxis to be targeted to patients at highest risk of developing CMV disease. It is critical to clearly define the risk factors for fungal and CMV disease in the individual patient in order to minimize adverse effects and provide the optimal prophylactic benefit.
 ...
PMID:Prophylaxis against fungal infections and cytomegalovirus disease after bone marrow transplantation. 1121 56

Invasive fungal infections play a key role in contributing to morbidity and mortality in patients undergoing treatment for haematological malignancies and related diseases. Risk factors for development of invasive fungal infections after blood or bone marrow transplantation include the use of broad-spectrum antibiotics, steroids, mismatched or unrelated donor transplant, right atrial catheters, and prolonged or profound neutropenia. Previous attempts at use of oral itraconazole as antifungal prophylaxis in the setting of chemotherapy-induced neutropenia were unsuccessful because of its poor absorption in capsule form. Itraconazole-cyclodextrin is well absorbed even in the presence of chemotherapy-induced neutropenia. Plasma levels of 250-500 ng/ml are required for prophylaxis. Studies to date show a favourable outcome in patients receiving itraconazole as prophylaxis against invasive fungal infections, although many studies looked at small numbers of patients and the incidence of invasive fungal infection in the control groups was low, prohibiting meaningful statistical evaluation. Fungi differ in their sensitivity to antifungal agents, and itraconazole is not the agent of choice in all patients. With the widespread use of antifungal prophylaxis, the possibility of resistance to antifungal agents and an increase in the number of invasive fungal infections caused by ubiquitous fungi previously considered nonpathogenic must be considered as potential problems.
 ...
PMID:The use of itraconazole as prophylaxis against invasive fungal infection in blood and marrow transplant recipients. 1142 15

The incidence and risk factors for fungal infection were assessed in 291 patients who had solid tumors and were undergoing autologous peripheral blood stem cell transplantation. The first 162 patients received prophylactic itraconazole, and 129 patients received nystatin. Empiric amphotericin B was given at day 7 of febrile neutropenia. Fungal infections developed in 52 patients: 47 (16%) were superficial and 6 (2%) were systemic. Itraconazole prophylaxis and only a few days of febrile neutropenia were independently associated with a decrease in the incidence of superficial infections. Only two patients required empiric amphotericin B. Systemic antifungal prophylaxis does not seem to be justified for patients with solid tumors and autologous peripheral blood stem cell transplantation. Empiric amphotericin B may be safely started at day 7 of febrile neutropenia.
 ...
PMID:Fungal infections in patients with solid tumors treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. 1168 37

Patients with acute leukemia are at high risk of fungal infection, suggesting that a preventive strategy is required. Fourteen patients receiving intensive chemotherapy for acute leukemia were studied to evaluate antifungal prophylaxis using itraconazole, and the plasma concentration of the drug was measured to determine its relationship to clinical efficacy. The median age of the patients was 50 years (range, 25 to 79 years), and all patients had neutropenia (less than 500 neutrophils/&mgr;l) which had lasted a median of 16 days (range, 4 to 30 days). Itraconazole was given orally at a dose of 200 mg (four capsules of 50 mg) once daily for at least 14 days. An H2-receptor antagonist was also given to prevent chemotherapy-induced gastrointestinal toxicity. Trough plasma concentrations of itraconazole and its metabolite, hydroxyitraconazole, were determined by reverse-phase high-performance liquid chromatography. The mean concentrations of itraconazole and hydroxyitraconazole on day 10 were 300 +/- 96 ng/ml (range, 131-428 ng/ml) and 776 +/- 369 ng/ml (range, 320-1582 ng/ml), respectively. There were marked inter-patient variations in both concentrations. No side effects were observed in the patients, and there was no definite fungal infection episode during this study. Daily oral administration of 200 mg of itraconazole appears to be effective as prophylaxis against fungal infection in neutropenic patients with acute leukemia. However, there were marked individual variations in the itraconazole plasma concentrations, which suggests that the plasma concentration should be monitored in patients with a risk of low absorption of this drug to adjust the dose given to an adequate level.
 ...
PMID:Plasma concentration of itraconazole and its antifungal prophylactic efficacy in patients with neutropenia after chemotherapy for acute leukemia. 1181 May 20

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as an induction therapy. The patient developed pneumonia and bacterial sepsis during profound neutropenia. Fever and sepsis improved by using many anti-bacterials and anti-fungals but he became febrile again and complained of severe lumbar pain. 67Ga scintigram showed abnormal uptake in the lumbar vertebra and left sternoclavicular joint, suggesting a diagnosis of discitis and osteomyelitis in the lumbar vertebra and sternoclavicular arthritis. We biopsied the site several times but culture of the biopsy specimen could not isolate any pathogens, and high fever persisted for about 10 months despite administration of various anti-bacterials and anti-fungals. Finally we inserted a catheter into the abscess at the iliopsoas muscle and Scedosporium apiospermum was isolated in the bloody pus obtained from the catheter. Itraconazole and amphotericin B were restarted, and the high fever and lumbar pain improved rapidly. The findings of S. apiospermum infection in this patient emphasizes the importance of being aware of this pathogen in patients with hematologic malignancy during the neutropenic phase.
 ...
PMID:Disseminated infection due to Scedosporium apiospermum in a patient with acute myelogenous leukemia. 1268 61

We assessed the impact of prophylaxis with the oral itraconazole solution and amphotericin B solution on fungal colonization and infection in a randomized study among patients with hematological malignancies and neutropenia. Infecting and colonizing Candida strains of patients suffering from candidiasis were genotyped by random amplification of polymorphic DNA (RAPD) analysis. A total of 106 patients were evaluated in this study: 52 patients in the itraconazole and 54 in the amphotericin B arm. During neutropenia fungal colonization in the oropharynx occurred in 11 (19.6%) and 24 (40.6%) and in the rectum in 11 (19.6%) and 23 (38.9%) courses in the itraconazole and amphotericin B groups ( P<0.05), respectively. Candida albicans was the most prevalent species in both study groups. Mixed fungal colonization with Candida krusei and Candida glabrata was increased in the amphotericin B group, yet without clinical importance since infections were due to C. albicans. The occurrence of invasive candidiasis was significantly increased in multicolonized compared to monocolonized patients. In the amphotericin B group 20 and in the itraconazole group 2 neutropenic patients showed multicolonization with Candida spp. ( P<0.05). Overall fungal infections were 3.8% in the itraconazole and 14.8% in the amphotericin B group ( P<0.05). RAPD typing showed oropharynx strains involved in superficial infections in four of five patients. In all four patients with deep fungal infections, it appears that the colonizing rectum strains were identical to infecting strains of Candida spp. Itraconazole solution significantly reduced Candida colonization and infection compared to amphotericin B solution. Most patients remained infected with the colonized strains for the entire study period, irrespective of antifungal prophylaxis.
 ...
PMID:Fungal colonization in neutropenic patients: a randomized study comparing itraconazole solution and amphotericin B solution. 1450 12

Antibiotics generally considered for antibacterial prophylaxis for immunosuppressed patients are trimethoprim-sulfamethoxazole and the quinolones. Trimethoprim-sulfamethoxazole can significantly reduce infections and is highly effective in preventing pneumonia due to Pneumocystis carinii. However, it can cause sulfonamide-related reactions, myelosuppression, oral candidiasis, and development of bacterial resistance, and it lacks activity against Pseudomonas aeruginosa. Quinolones can reduce the occurrence of fever and infections in patients with neutropenia but do not provide adequate coverage against gram-positive bacteria, and inappropriate use can induce resistance among gram-negative organisms. Routine antibacterial prophylaxis is not recommended for patients likely to develop neutropenia. Antifungal prophylaxis is appropriate in settings in which fungal infections are frequent. Fluconazole is recommended for patients who are to undergo hematopoietic stem cell transplantation; it can be considered for elderly patients with acute leukemia who are to receive intensive chemotherapy. Itraconazole can also be used. Prophylaxis with antiviral agents is generally not indicated; however, it should be given to hematopoietic stem cell transplant recipients.
 ...
PMID:Antimicrobial prophylaxis in febrile neutropenia. 1525 25

Infection is one of the main causes of death in patients with hemoblastoses. Within the last years there was observed an increase in the ratio of fungal infections in the structure of mortality among hematologic patients with neutropenia. The present study was aimed at comparative estimation of the efficacy of the prophylactic use of various azole antifungal agents in patients with hematologic neoplasms and severe neutropenia. The trial enrolled 88 patients comparable by the diagnosis and chemotherapy characteristics, in whom severe neutropenia developed after intensive therapy. Antifungal drugs were used prophylactically when the neutrophil count lowered below 1.0 x 10(9)/l until its increasing above 1.0 x 10(9)/l or when the signs of fungal infection were evident. Itraconazole was used in cyclodextrin solution in 30 patients in a dose of 0.2 g orally twice a day and fluconazole was used in capsules in 24 patients in a dose of 0.2 g orally once a day. The results were compared with those of the ketoconazole use in a dose of 0.2 g orally twice a day (n = 34). The frequency of fungal infection proved by the clinical documentation was 20.5% in the ketoconazole group (k) (7 out of 34 patients), 8.3% in the fluconazole group (f) (2 out of 24 patients) and 6.6% in the itraconazole group (i) (2 out of 30 patients), p (k-f) = 0.21, p (k-i) = 0.11 and p (f-i) = 0.74. The frequency of fungal infection proved by the microbiological documentation was statistically much higher in the ketoconazole group (38.2%) vs. the fluconazole group (8.3%) (p = 0.013) and the itraconazole group (6.6%) (p = 0.004). The prophylactic use of itraconazole and fluconazole was efficient in preventing development of invasive mycoses in the patients with hemoblastoses and severe neutropenia. Their efficacy was much higher than that of ketoconazole.
 ...
PMID:[Prophylaxis of fungal infection in patients with hematologic neoplasms and severe neutropenia after high-dose chemotherapy]. 1572 47


<< Previous 1 2 3 Next >>