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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Invasive fungal infections (IFI) parallel the explosive increase in the immunocompromized patient population, and are characterized by diagnostic difficulties and extreme mortality. Candidemia in a tertiary referral hospital in the Middle East confirms the current epidemiologic shift in this common blood stream pathogen towards non-malignancy cases (38%) and antifungal prophylaxis failure (20%), high presentation sepsis scores and attributable mortality (32%). Invasive aspergillosis (IA) is also associated with high mortality. Use of non-invasive computerized tomographic (CT) radiologic scanning linked to early administration of high dose liposomal amphotericin B (LAB) is associated with a reduced mortality of 9.5% compared to historical experience of 28%.Life threatening invasive aspergillosis also occurs in patients who are less obviously immunocompromized. Investigations may reveal subtle immune deficits which could place the patient at some risk for an invasive mycosis. Antifungal treatment used in combination with progenitor cell growth factors and gamma-interferon has proved successful in such situations of progressive fungal disease unresponsive to antifungal therapy alone. Pharmacologic remodeling of existing compounds by lipidisation reduces both the toxicity denominator and the efficacy numerator of the therapeutic index when compared to the parent drug. A comparative dose study of liposomal amphotericin B in aspergillosis has demonstrated equi-efficacy, generated debate over the ability of the controlled clinical trial to be capable of assessing antifungal efficacy, and illustrated that recovery from an invasive fungal infection may require maximum tolerated doses and immunomanipulation. Several new antifungal strategies are under clinical investigation. These include reformulating existing antifungals, exploitation of the growing knowledge of virulence factors to synthesize antagonists, immune reconstitution and immunoprotection. An interim analysis of an ongoing placebo controlled study of recombinant interleukin-11 to assess its efficacy in reducing sepsis in leukemia patients through prevention of chemotherapy induced gut epithelial cell apoptosis, has demonstrated a difference in the two study arms in sepsis rates and preservation of gastrointestinal epithelial cell integrity. The unique and special challenges presented by the dynamic epidemiologics of invasive fungal infections are demanding and attracting considerable responses, in the fields of diagnosis and therapeutics. Current strategies need considerable improvement, yet ongoing collaborative efforts will have a positive impact on our understanding of the fungus-host interaction and ultimately our ability to offer better care for our patients with invasive mycoses.
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PMID:Invasive fungal infections: evolving challenges for diagnosis and therapeutics. 1200 73

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.
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PMID:Candidemia in a tertiary care cancer center: in vitro susceptibility and its association with outcome of initial antifungal therapy. 1453 Jul 80

Candidaemia due to non-albicans Candida species is increasing in frequency. We describe 272 episodes of candidaemia, define parameters associated with Candida albicans and other Candida species, and analyse predictors associated with mortality. Patients with C. albicans (55%) had the highest fatality rate and frequently received immunosuppressive therapy, while patients with Candida parapsilosis (16%) had the lowest fatality and complication rates. Candida tropicalis (16%) was associated with youth, severe neutropenia, acute leukaemia or bone marrow transplantation, Candida glabrata (10%) was associated with old age and chronic disease, and Candida krusei (2%) was associated with prior fluconazole therapy. The overall fatality rate was 36%, and predictors of death by multi-variate analysis were shock, impaired performance status, low serum albumin and congestive heart failure. Isolation of non-albicans Candida species, prior surgery and catheter removal were protective factors. When shock was excluded from analysis, antifungal therapy was shown to be protective. Unlike previous concerns, infection with Candida species other than C. albicans has not been shown to result in an increased fatality rate.
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PMID:Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality. 1600 56

The incidence of non-albicans species of Candida has recently increased, especially in patients with malignant haematological disorders receiving fluconazole prophylaxis. A retrospective study of patients who developed candidaemia at Riyadh Armed Forces Hospital between January 1992 and December 2002 was carried out. Thirty one episodes of candidaemia occurred in 27 patients with a variety of haematological disorders. Twenty-four episodes were caused by non-albicans species of Candida and only 7 episodes were caused by C.albicans. The most frequent underlying haematological disorders were acute myeloid leukaemia (AML) followed by acute lymphoblastic leukaemia (ALL). The main predisposing factors for the development of candidaemia were: broad spectrum antibiotics, central venous catheters, neutropenia, cytotoxic chemotherapy, coexisting bacterial infections, steroid therapy, relapsing or untreated primary disease and fluconazole prophylaxis.Eight episodes were complicated by chronic disseminated candidiasis. Amphotericin-B and amBisome were used in the treatment of Candida infections. The treatment was successful in 86% of the episodes of C. albicans and 50% of the episodes due to nonalbicans species of Candida. The highest mortality rate was encountered with C.tropicalis infections.Candidaemia is an important cause of mortality and morbidity in patients with malignant haematological disorders and stem cell transplant. The predominance of non-albicans species of Candida especially C.krusei and C.tropicalis is alarming. The early administration of appropriate antifungal therapy and the removal of infected intravascular catheters improve the outcome considerably.
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PMID:Candidaemia in patients with haematological disorders and stem cell transplant. 2152 12