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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amphotericin B therapy for fever during neutropenia became a standard practice approximately 20 years ago. Treatment of febrile neutropenia has since become a common indication sought in the development of new antifungals, with several alternatives approved for 'empirical therapy' based on the results of randomized clinical trials. Recent studies have highlighted problematic issues in trial design and interpretation; inclusion criteria and the definition of success are two examples of controversial issues. Here, issues in trial design will be reviewed to address the question: Can (and should) new antifungals be evaluated for treatment of fever during neutropenia?
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PMID:Antifungal therapy for febrile neutropenia: issues in clinical trial design. 1504 95

Amphotericin B remains the drug of choice for the treatment of invasive fungal infections and visceral leishmaniasis. However, both the dose-dependent nephrotoxicity and the low response rates (10-80%) associated with amphotericin B limit its clinical use. The first marketed formulation of amphotericin B with deoxycholate, Fungizone, remains the "gold standard" in spite of its renal toxicity. Several investigations have been made to reduce the nephrotoxicity of amphotericin B by formulation strategies. Lipid-based formulations of amphotericin B were found to reduce toxicity and to increase tolerance and therapeutic efficacy. Three lipid formulations are now available in most countries: liposomal amphotericin B (AmBisome), amphotericin B lipid complex and amphotericin B colloidal dispersion. Amphotericin B colloidal dispersion was less nephrotoxic, but immediate reactions to this formulation were as frequent and severe as those to amphotericin B. Amphotericin B lipid complex appeared to be as effective as amphotericin B, with improved general and renal tolerability. Several comparative studies have confirmed that AmBisome has similar or superior efficacy relative to amphotericin B in various fungal infections, in visceral leishmaniasis and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. A significant drawback to the newer, less toxic, commercial lipid-based formulations is their cost. There is a need to develop more affordable lipid-based formulations of amphotericin B.
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PMID:Lipid-based formulations of amphotericin B. 1504 35

A 30-year-old man with acute myeloid leukemia who was pancytopenic after undergoing intensive chemotherapy developed pyrexia and severe pain of both lower legs. We immediately started empiric therapy with cefepime, vancomycin, and fluconazole for febrile neutropenia. However, symptoms progressed. After 4 days, Trichosporon was isolated from venous blood cultures. MRI showed hyperintense lesions within both gastrocnemius muscles and demonstrated reactive vasodilatation and interstitial tissue edema, thought to be induced by hyperpermeability of vessel membranes due to the local fungal infection. Amphotericin B was very effective against this organism. Trichosporosis is a rare infectious disease generally occurring in immunocompromized hosts. To the best of our knowledge, this is first reported case of bilateral Trichosporon infection of lower leg muscles. Severe leg pain was one of the most important signs of fungal infection in this patient with hematologic malignancy.
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PMID:The usefulness of magnetic resonance imaging (MRI) for disseminated trichosporosis of the gastrocnemius muscles. 1643 3

Hematopoietic stem cell transplant recipients and those patients with acute leukemia are at greatest risk for invasive fungal infections particularly due to Candida and Aspergillus species during periods of profound neutropenia. Empiric antifungal therapy in persistently febrile neutropenic patients has been adopted as a standard of care. Antifungal therapeutic options include: amphotericin B, lipid formulations of amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin. Amphotericin B preparations offer a beneficial effect for survival, defervescence, and a decrease in breakthrough fungal infections. Lipid formulations of amphotericin B may provide beneficial effects over amphotericin B with regard to survival, treatment of baseline fungal infection, breakthrough fungal infection, and fewer discontinuations due to lack of efficacy. Amphotericin B compounds produce a trend for better outcomes in defervescence, treatment of baseline fungal infections, prevention of breakthrough infections, and avoidance of discontinuation compared with the azoles. Caspofungin is also effective. The optimal empiric antifungal agent and the precise time of initiation remain to be determined.
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PMID:Empiric antifungal therapy in neutropenic cancer patients. 1644 95

Fever is the principle sign of infection in neutropenic patient and frequently may be the only evidence of infection. The pattern of fever in neutropenia is non-specific and not pathognomonic of any type of infections or non-infectious process and can be suppressed by the antipyretic effects of drugs such as corticosteroids. Neutropenia, resulting from cytotoxic chemotherapy is the most common risk factor for severe infections in hematological malignancies. The duration of neutropenia also contributes significantly to the risk of serious infections. This risk is significantly greater a lower neutrophil counts, such that 100% patients with ANC <100 cells/microl lasting 3 weeks or more develop documented infections. The prompt initiation of empirical antibiotics in febrile neutropenia has been the most important advance in the management of the immunocompromised host. The initial empirical antibiotic regimen started at presentation of the febrile episode frequently requires modifications especially in high-risk febrile neutropenia. Neutropenic patients who remain febrile despite 4-7 days of broad spectrum antibacterial therapy are at a high risk of invasive fungal infection. Empirical antifungal therapy with Amphotericin B in persistently febrile neutropenic patients and other high risk patients has shown to reduce the risk of invasive fungal infection by 50-80% and the risk of fungal infection related mortality by 23-45% in 1980's. The IDSA has recommended that amphotericin B at 0.5-0.7 mg/kg/day be administered till marrow recovery. This approach is limited however by the adverse effects caused by drug infusion (fever, chills, myalgias, nausea, hypotension and bronchospasm). Lipid formulations which improve the therapeutic ratio of the traditional formulation are available. The safety and efficacy of these formulations is well established. These formulations have comparable efficacy and are less nephrotoxic than conventional amphotericin B.A lipid formulation of amphotericin B is appropriate as initial empirical therapy or as definitive therapy for proven mycosis in high risk patients receiving concomitant nephrotoxic drugs (cyclosporine), those with pre-existing renal impairment and those with protracted neutropenia during which dose limiting toxicity may occur.
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PMID:Febrile neutropenia in haematological malignancies. 1651 55

The description of the association between the use of amphotericin-B (amB) and the development of systemic arterial hypertension was only anecdotal so far. We describe the case of a 19-year-old female patient who had acute lymphoblastic leukemia and developed prolonged neutropenia after reinduction chemotherapy. Candida parapsilosis was isolated from blood cultures, and amB was started. Sustained severe arterial hypertension developed shortly after amB administration and continued for several hours after the infusion. Aldosterone, blood urea nitrogen, and creatinine levels were normal. After clinical improvement, amB was replaced by fluconazole, and blood pressure normalized. Severe hypertension may be an adverse event associated with AmB treatment that requires intensive treatment.
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PMID:Amphotericin B-induced severe hypertension in a young patient: case report and review of the literature. 1653 79

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.
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PMID:Treatment options of invasive fungal infections in adults. 1693 23

Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic mice with disseminated candidiasis caused by one of three strains of Candida glabrata. Anidulafungin produced a maximal fungal kill (E(max)) of 1.4 to 1.9 log(10) CFU/g in kidneys and was not influenced by resistance to either fluconazole or amphotericin B. Fluconazole produced an E(max) of 1.3 log(10) CFU/g in mice infected with fluconazole-susceptible C. glabrata, but the E(max) was 0 for mice infected with a C. glabrata strain that had a fluconazole MIC of >/=32 mg/liter. Amphotericin B achieved an E(max) of 4.2 log(10) CFU/g in mice infected with amphotericin B-susceptible C. glabrata, but the E(max) was 0 for mice infected with a C. glabrata strain with an amphotericin B MIC of 2 mg/liter. In all instances, anidulafungin's maximal microbial kill was superior to that of fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic-pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in kidneys compared to those in serum, after which the concentrations declined, with a serum terminal half-life of 21.6 (+/-4.6) h. This was accompanied by a persistent 96-h decrease in the kidney fungal burden after treatment with a single anidulafungin dose of >/=8 mg/kg of body weight. This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia.
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PMID:Anidulafungin pharmacokinetics and microbial response in neutropenic mice with disseminated candidiasis. 1695 19

Among patients with haematologic disorders, mucormycosis most commonly occurs in those with acute leukaemia or lymphoma who have developed neutropenia due to malignancy or to chemotherapy, and in transplanted patients receiving immunosuppressive treatment. Here, we aim to present a retrospective study conducted over a 5-year period (2001-2005). The study included 20 patients with haematologic malignancies with a proven mucormycosis admitted in Medical Oncology Divisions in Cukurova University Hospital. The most frequent sites of infection were paranasal sinuses (95%) and lung (5%). Antifungal treatment was empirically administered in 18 (90%) patients; 18 patients underwent radical surgical debridement (90%). The therapy was successful for only eight patients (40%). Eleven patients died within 1 months of the diagnosis of fungal infection: the cause of death was only by mucormycosis in four patients (36.6%), mucormucosis and systematic inflamatuar response syndrome (SIRS) in two patients (18.2%) and progression of haematologic disease in five patients (45.5%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: amphotericin B treatment, neutrophil recovery from postchemotherapy aplasia. At multivariate analysis, the factors that significantly correlated with recovery from infection were the liposomal amphotericin B treatment (p = 0.026), doses of L-AmB (p = 0.008) and the length of the treatment (p = 0.01), respectively. It seems to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.
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PMID:Mucormycosis-associated fungal infections in patients with haematologic malignancies. 1736 81

A 5-year-old boy had a 10-month remission of acute lymphocytic leukemia (ALL) after chemotherapy. Re-induction chemotherapy was performed for relapse of ALL. Thereafter, he suffered from an episode of neutropenic fever with pneumonia. One week following control of the condition with antibiotics, a 1 x 1-cm, red, painful nodule appeared on the left thigh, which was initially suspected to be Pseudomonas infection. Parenteral ceftazidime and amikacin were administered, but persistent high fever, mild cough, and a few painful erythematous papulonodules on the face and lower extremities appeared several days later (Fig. 1). These lesions increased insidiously in diameter up to 2-5 cm with central necrosis. Hemogram showed neutropenia with a shift to the left [white blood cell (WBC) count, 2.1 x 10(9)/L; neutrophil count, 0.21 x 10(9)/L]. A skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis, together with fat necrosis (Fig. 2). Invasion of molds into vessels and sweat glands was also seen. A culture from a lesion yielded Fusarium moniliforme, but no fungi were isolated from blood specimens. Only mild infiltrations on bilateral lower lung fields were detected by chest roentgenography. The skin lesions gradually healed and the fever subsided 2 weeks after the initiation of therapy with amphotericin B 30 mg and itraconazole 200 mg daily. Meanwhile, relapse of leukemia was detected by hemogram showing atypical leukocytosis (WBC count of 24,400 x 10(9)/L, with blast cells representing 78%). A course of chemotherapy with cytarabine, mitoxantrone, and VP-16 was prescribed, subsequently resulting in neutropenia (WBC count, < 0.1 x 10(9)/L; neutrophil count, 0/L) and spiking fever. Although the aforementioned antifungal therapy was continued, the centers of the originally healed lesions turned dusky red, swollen, necrotic, and ulcerative. There were more than 10 such ecthymiform lesions. After administration for 22 days, itraconazole was discontinued because of no appreciable effects. Granulocyte colony-stimulating factor (G-CSF) salvage was used, and the neutropenia gradually subsided 20 days later. In addition, the ecthymiform lesions gradually resolved. Amphotericin B was discontinued 1 week following neutrophil recovery. The patient died of Acinetobacter baumannii and Stenotrophomonas maltophilia sepsis 8 months later.
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PMID:Disseminated cutaneous Fusarium moniliforme infections in a leukemic child. 1747 77


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