International Journal of Infectious Diseases, 2012
Candidemia affects patient populations from neonates to the elderly. Despite this, little informa... more Candidemia affects patient populations from neonates to the elderly. Despite this, little information is available about the epidemiology of candidemia in elderly patients. We performed a retrospective analysis of 987 episodes of candidemia in adults (>14 years of age) from the databases of three laboratory-based surveys of candidemia performed at 14 tertiary care hospitals. Patients aged ≥60 years were considered elderly (group 1, n=455, 46%) and were compared to younger patients (group 2, n=532, 54%) regarding demographics, underlying diseases, comorbidities, exposure to medical procedures, species, treatment, and outcome. The median APACHE II score was significantly higher in the elderly patients (19 vs. 15, p=0.03). Variables that were observed significantly more frequently in elderly patients included admission to an intensive care unit, diabetes mellitus, renal failure, cardiac disease, lung disease, receipt of antibiotics or H2 blockers, insertion of a central venous catheter, mechanical ventilation, and candidemia due to Candida tropicalis. The 30-day mortality of elderly patients was significantly higher than that of younger patients (70% vs. 45%, p<0.001). Factors associated with higher mortality by multivariate analysis included APACHE II score and being in group 1 (elderly). Factors associated with mortality in elderly patients were lung disease and the receipt of mechanical ventilation. Elderly patients account for a substantial proportion of patients with candidemia and have a higher mortality compared to younger patients.
Invasive fungal disease represents a major complication in hematological patients. Antifungal age... more Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of antifungal use, as well as the pharmacologic proprieties of the different antifungal agents. In this paper the principal antifungal agents used in hematologic patients will be discussed as will the clinical scenarios where these agents have been used.
We aimed to assess the characteristics, treatment, risk factors and outcome of patients with brea... more We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicenter study of hospitalized adults with candidemia at six hospitals in three countries. BrC episodes were compared to the remaining (non-BrC). Of 409 episodes of candidemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% vs. 46%, p=.010) whereas C. krusei was more frequent (16% vs. 2.4%, p<.001). BrC was associated with infections due to fluconazole non-susceptible isolates (50% vs. 18%, p<.001). C. albicans BrC was associated with prior fluconazole treatment while C. parapsilosis candidemia was mostly catheter-related and/or associated with prior echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% vs. 74%, p=.055). No significant differences were found in outcomes (early and overall mortality: 11% vs. 13% p=.802 and 40% vs. 40% p=.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (AOR, 5.57; 95% CI, 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicenter cohort. The Candida spp. isolated were different depending on the prior antifungal therapy: prior azole treatment was associated with fluconazole non-susceptible strains and prior echinocandin with BrC candidemia caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.
Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective stu... more Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective studies show that shorter times to treatment are correlated with a lower risk of death. A number of factors can be used to predict which patients would benefit from antifungal prophylaxis or early (pre-emptive or empirical) therapy. Detection of the fungal cell wall component (1-->3)-beta-D-glucan (BDG) shows promise as
Transplant infectious disease : an official journal of the Transplantation Society, 2015
The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoiet... more The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoietic cell transplant (HCT) recipients may vary according to the region. In this study, we sought to evaluate risk factors for IMD in our patient population. Between May 2007 and July 2009, all HCT recipients from 8 Brazilian centers were followed prospectively until 1 year post transplant. Cases of IMD were classified as early (before day +40) or late (after day +40). Patients with IMD (cases) were compared with controls (patients without IMD) using univariate and multivariate Cox regression analysis. Among 345 HCT recipients, 28 IMDs were diagnosed. Risk factors for early IMD were acute myeloid leukemia (hazard ratio [HR] 2.95, 95% confidence interval [95% CI] 1.13-7.68, P = 0.03) and transplant with a human leukocyte antigen-mismatched donor (HR 3.38, 95% CI 1.18-9.68, P = 0.02), and for late IMD risk factors were lymphoma (HR 8.49, 95% CI 2.35-30.68, P = 0.001), cytomegalovirus reactiva...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2015
Risk factors for invasive fusariosis (IF) have not been characterized. We attempted to identify r... more Risk factors for invasive fusariosis (IF) have not been characterized. We attempted to identify risk factors for IF in a prospective cohort of hematologic patients treated in 8 centers in Brazil. Patients with (cases) and without (controls) proven or probable IF diagnosed in a cohort of patients with acute myeloid leukemia (AML) or myelodysplasia (MDS), and in allogeneic hematopoietic cell transplant (HCT) recipients (early, until day 40; late, after day 40 posttransplant) were compared by univariate Cox regression analysis. Among 237 induction remission courses of AML/MDS and 663 HCTs (345 allogeneic and 318 autologous), 25 cases of IF were diagnosed. In the AML/MDS cohort, active smoking (hazard ratio [HR], 9.11 [95% confidence interval {CI}, 2.04-40.71]) was associated with IF. Variables associated with IF in the early phase of allogeneic HCT were receipt of antithymocyte globulin (HR, 22.77 [95% CI, 4.85-101.34]), hyperglycemia (HR, 5.17 [95% CI, 1.40-19.11]), center 7 (HR, 5.15...
A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% de... more A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in a fat emulsion (Intralipid) in cancer patients. Group 1 (n = 33) received amphotericin B diluted in 5% dextrose with premedication consisting of promethazine plus an antipyretic. Group 2 (n = 28) received amphotericin B diluted in 20% Intralipid without premedication. Amphotericin B was infused daily at a dose of 1 mg/kg of body weight over a 1-h period to members of both groups for empirical antifungal therapy (in neutropenic patients) or for the treatment of documented fungal infections. The majority of patients (80%) received empirical amphotericin B treatment. The two groups were comparable with regard to age, gender, underlying disease, and the following baseline characteristics: use of other nephrotoxic drugs and serum levels of potassium and creatinine. The median cumulative doses of amphotericin B were 240 mg in group 1 and 245 mg in group 2 ...
The objective of this study was to characterize the epidemiology of candidemia in cancer patients... more The objective of this study was to characterize the epidemiology of candidemia in cancer patients in the city of Rio de Janeiro, Brazil. An 18-month survey of fungemia in patients with cancer was undertaken in three Hospitals in Rio de Janeiro. Forty-three episodes of candidemia were identified in 43 patients, 43 of which were episodes of candidemia; in ten case the strains were not available for further identification of species and were excluded from this analysis. The overall distribution of fungi causing fungemia was: Candida albicans (5), Candida tropicalis (16), Candida parapsilosis (6), Candida guilliermondii (4), Candida lusitaniae (1) and Candida stellatoidea (1). Antifungal prophylaxis had been administered before the episode of fungemia in only six patients (18.2%): oral itraconazole in three patients and oral nistatin, low dose intravenous amphotericin B and oral fluconazole in one patient each. There was no difference in the presence of risk factors, clinical characteri...
We report on a case of mixed infection caused by two species of Fusarium in a human immunodeficie... more We report on a case of mixed infection caused by two species of Fusarium in a human immunodeficiency virus-positive patient with lymphoma who was neutropenic due to chemotherapy. The patient showed the typical signs of a disseminated fusarial infection, with Fusarium solani isolated from skin lesions and F. verticillioides isolated from blood. The report discusses how difficult it is to make an accurate diagnosis when an immunosuppressed patient is infected with more than one fungal species, especially when the species are morphologically very similar.
Jornal Brasileiro de Patologia e Medicina Laboratorial, 2002
resumo A classificação dos linfomas não-Hodgkin tem sido, ao longo dos últimos trinta anos, motiv... more resumo A classificação dos linfomas não-Hodgkin tem sido, ao longo dos últimos trinta anos, motivo de controvérsia. Várias classificações têm sido propostas em busca de um consenso entre patologistas e clínicos. Este trabalho teve como objetivo analisar ...
Persistent candidemia refers to the continued isolation of the same Candida species in the blood ... more Persistent candidemia refers to the continued isolation of the same Candida species in the blood of a candidemic patient. Its incidence and clinical consequences are not well understood because of the lack of a homogeneous definition for persistent candidemia and the absence of prospective studies in which blood cultures were performed at prespecified times. Data from randomized clinical trials indicate that between 8% and 15% of candidemic patients have persistently positive blood cultures at the end of treatment, and the few studies that have attempted to evaluate the impact of persistent candidemia on outcomes have lacked appropriate analysis to conclude whether persistent candidemia is associated with worse outcome. On the other hand, assuming that it represents therapeutic failure, major causes for persistent candidemia include host factors (probably the most important), drug resistance, low serum levels of drugs, endovascular infection, deep-tissue abscesses, and infection associated with prosthetic material.
... 6. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, et al. ... Correspondence: M... more ... 6. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, et al. ... Correspondence: Marcio Luiz Moore Nucci Rua Professor Rodolpho Paulo Rocco, 255 – 4º andar, sala 4/12 – Ilha do Fundão 21.941-913 – Rio de Janeiro-RJ – Brasil Tel.: (55 21) 2562-2463 E-mail ...
Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare m... more Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare micafungin with liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidosis. We did a double-blind, randomised, multinational non-inferiority study to compare micafungin (100 mg/day) with liposomal amphotericin B (3 mg/kg per day) as first-line treatment of candidaemia and invasive candidosis. The primary endpoint was treatment success, defined as both a clinical and a mycological response at the end of treatment. Primary analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT00106288. 264 individuals were randomly assigned to treatment with micafungin; 267 were randomly assigned to receive liposomal amphotericin B. 202 individuals in the micafungin group and 190 in the liposomal amphotericin B group were included in the per-protocol analyses. Treatment success was observed for 181 (89.6%) patients treated with micafungin and 170 (89.5%) patients treated with liposomal amphotericin B. The difference in proportions, after stratification by neutropenic status at baseline, was 0.7% (95% CI -5.3 to 6.7). Efficacy was independent of the Candida spp and primary site of infection, as well as neutropenic status, APACHE II score, and whether a catheter was removed or replaced during the study. There were fewer treatment-related adverse events--including those that were serious or led to treatment discontinuation--with micafungin than there were with liposomal amphotericin B. Micafungin was as effective as--and caused fewer adverse events than--liposomal amphotericin B as first-line treatment of candidaemia and invasive candidosis.
Invasive fungal diseases (IFDs) represent an important cause of treatment failure in adults with ... more Invasive fungal diseases (IFDs) represent an important cause of treatment failure in adults with acute leukemia. Because of leukemia's heterogeneity, the risk for IFDs is highly variable. We therefore apply a risk-adapted antifungal strategy with strong emphasis on pretreatment and day-15 posttreatment to allow earlier and more individualized interventions. We determine pretreatment risks for IFDs based on 4 factors: (1) host fitness for standard therapy (ie, fit, unfit, or frail); (2) leukemia resistance (high vs low probability of achieving complete remission [CR]); (3) anticipated treatment-related toxicity such as neutropenia, mucositis, and steroid-induced immunosuppression; and (4) patient exposure to opportunistic fungi. Accordingly, we stratify patients as high, intermediate, or low risk for IFDs and apply risk-adapted antifungal strategies, including primary or secondary prophylaxis and diagnostic-based preemptive or empiric therapy. Prevention of IFDs also relies on optimizing organ function, decreasing exposure to opportunistic fungi, and improving net state of immunosuppression with use of better-tolerated and investigational agents for unfit patients and those with adverse leukemia biology. Novel targeted and safe therapies that can achieve higher rates of sustained CR among patients with adverse genetics offer the best promise for reducing the burden of IFDs in these patients.
The management of chronic myeloid leukemia (CML) has changed radically since the introduction of ... more The management of chronic myeloid leukemia (CML) has changed radically since the introduction of imatinib therapy. The decision of whether to offer a patient a hematopoietic stem cell transplant (HSCT) must be based on the probability of success of the procedure. The aim of this retrospective analysis of 1,084 CML patients who received an allogeneic HSCT in 10 Brazilian Centers between February 1983 and March 2003 was to validate the EBMT risk score. The study population comprised 647 (60%) males and 437 (40%) females, with a median age of 32 years old (range 1 - 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1,025 (94%) received an HLA fully matched sibling transplant and only 59 (6%) received an unrelated transplant. In 283 cases (26%) a male recipient received a graft from a female donor. The interval from diagno...
International Journal of Infectious Diseases, 2012
Candidemia affects patient populations from neonates to the elderly. Despite this, little informa... more Candidemia affects patient populations from neonates to the elderly. Despite this, little information is available about the epidemiology of candidemia in elderly patients. We performed a retrospective analysis of 987 episodes of candidemia in adults (>14 years of age) from the databases of three laboratory-based surveys of candidemia performed at 14 tertiary care hospitals. Patients aged ≥60 years were considered elderly (group 1, n=455, 46%) and were compared to younger patients (group 2, n=532, 54%) regarding demographics, underlying diseases, comorbidities, exposure to medical procedures, species, treatment, and outcome. The median APACHE II score was significantly higher in the elderly patients (19 vs. 15, p=0.03). Variables that were observed significantly more frequently in elderly patients included admission to an intensive care unit, diabetes mellitus, renal failure, cardiac disease, lung disease, receipt of antibiotics or H2 blockers, insertion of a central venous catheter, mechanical ventilation, and candidemia due to Candida tropicalis. The 30-day mortality of elderly patients was significantly higher than that of younger patients (70% vs. 45%, p<0.001). Factors associated with higher mortality by multivariate analysis included APACHE II score and being in group 1 (elderly). Factors associated with mortality in elderly patients were lung disease and the receipt of mechanical ventilation. Elderly patients account for a substantial proportion of patients with candidemia and have a higher mortality compared to younger patients.
Invasive fungal disease represents a major complication in hematological patients. Antifungal age... more Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of antifungal use, as well as the pharmacologic proprieties of the different antifungal agents. In this paper the principal antifungal agents used in hematologic patients will be discussed as will the clinical scenarios where these agents have been used.
We aimed to assess the characteristics, treatment, risk factors and outcome of patients with brea... more We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicenter study of hospitalized adults with candidemia at six hospitals in three countries. BrC episodes were compared to the remaining (non-BrC). Of 409 episodes of candidemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% vs. 46%, p=.010) whereas C. krusei was more frequent (16% vs. 2.4%, p<.001). BrC was associated with infections due to fluconazole non-susceptible isolates (50% vs. 18%, p<.001). C. albicans BrC was associated with prior fluconazole treatment while C. parapsilosis candidemia was mostly catheter-related and/or associated with prior echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% vs. 74%, p=.055). No significant differences were found in outcomes (early and overall mortality: 11% vs. 13% p=.802 and 40% vs. 40% p=.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (AOR, 5.57; 95% CI, 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicenter cohort. The Candida spp. isolated were different depending on the prior antifungal therapy: prior azole treatment was associated with fluconazole non-susceptible strains and prior echinocandin with BrC candidemia caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.
Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective stu... more Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective studies show that shorter times to treatment are correlated with a lower risk of death. A number of factors can be used to predict which patients would benefit from antifungal prophylaxis or early (pre-emptive or empirical) therapy. Detection of the fungal cell wall component (1-->3)-beta-D-glucan (BDG) shows promise as
Transplant infectious disease : an official journal of the Transplantation Society, 2015
The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoiet... more The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoietic cell transplant (HCT) recipients may vary according to the region. In this study, we sought to evaluate risk factors for IMD in our patient population. Between May 2007 and July 2009, all HCT recipients from 8 Brazilian centers were followed prospectively until 1 year post transplant. Cases of IMD were classified as early (before day +40) or late (after day +40). Patients with IMD (cases) were compared with controls (patients without IMD) using univariate and multivariate Cox regression analysis. Among 345 HCT recipients, 28 IMDs were diagnosed. Risk factors for early IMD were acute myeloid leukemia (hazard ratio [HR] 2.95, 95% confidence interval [95% CI] 1.13-7.68, P = 0.03) and transplant with a human leukocyte antigen-mismatched donor (HR 3.38, 95% CI 1.18-9.68, P = 0.02), and for late IMD risk factors were lymphoma (HR 8.49, 95% CI 2.35-30.68, P = 0.001), cytomegalovirus reactiva...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2015
Risk factors for invasive fusariosis (IF) have not been characterized. We attempted to identify r... more Risk factors for invasive fusariosis (IF) have not been characterized. We attempted to identify risk factors for IF in a prospective cohort of hematologic patients treated in 8 centers in Brazil. Patients with (cases) and without (controls) proven or probable IF diagnosed in a cohort of patients with acute myeloid leukemia (AML) or myelodysplasia (MDS), and in allogeneic hematopoietic cell transplant (HCT) recipients (early, until day 40; late, after day 40 posttransplant) were compared by univariate Cox regression analysis. Among 237 induction remission courses of AML/MDS and 663 HCTs (345 allogeneic and 318 autologous), 25 cases of IF were diagnosed. In the AML/MDS cohort, active smoking (hazard ratio [HR], 9.11 [95% confidence interval {CI}, 2.04-40.71]) was associated with IF. Variables associated with IF in the early phase of allogeneic HCT were receipt of antithymocyte globulin (HR, 22.77 [95% CI, 4.85-101.34]), hyperglycemia (HR, 5.17 [95% CI, 1.40-19.11]), center 7 (HR, 5.15...
A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% de... more A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in a fat emulsion (Intralipid) in cancer patients. Group 1 (n = 33) received amphotericin B diluted in 5% dextrose with premedication consisting of promethazine plus an antipyretic. Group 2 (n = 28) received amphotericin B diluted in 20% Intralipid without premedication. Amphotericin B was infused daily at a dose of 1 mg/kg of body weight over a 1-h period to members of both groups for empirical antifungal therapy (in neutropenic patients) or for the treatment of documented fungal infections. The majority of patients (80%) received empirical amphotericin B treatment. The two groups were comparable with regard to age, gender, underlying disease, and the following baseline characteristics: use of other nephrotoxic drugs and serum levels of potassium and creatinine. The median cumulative doses of amphotericin B were 240 mg in group 1 and 245 mg in group 2 ...
The objective of this study was to characterize the epidemiology of candidemia in cancer patients... more The objective of this study was to characterize the epidemiology of candidemia in cancer patients in the city of Rio de Janeiro, Brazil. An 18-month survey of fungemia in patients with cancer was undertaken in three Hospitals in Rio de Janeiro. Forty-three episodes of candidemia were identified in 43 patients, 43 of which were episodes of candidemia; in ten case the strains were not available for further identification of species and were excluded from this analysis. The overall distribution of fungi causing fungemia was: Candida albicans (5), Candida tropicalis (16), Candida parapsilosis (6), Candida guilliermondii (4), Candida lusitaniae (1) and Candida stellatoidea (1). Antifungal prophylaxis had been administered before the episode of fungemia in only six patients (18.2%): oral itraconazole in three patients and oral nistatin, low dose intravenous amphotericin B and oral fluconazole in one patient each. There was no difference in the presence of risk factors, clinical characteri...
We report on a case of mixed infection caused by two species of Fusarium in a human immunodeficie... more We report on a case of mixed infection caused by two species of Fusarium in a human immunodeficiency virus-positive patient with lymphoma who was neutropenic due to chemotherapy. The patient showed the typical signs of a disseminated fusarial infection, with Fusarium solani isolated from skin lesions and F. verticillioides isolated from blood. The report discusses how difficult it is to make an accurate diagnosis when an immunosuppressed patient is infected with more than one fungal species, especially when the species are morphologically very similar.
Jornal Brasileiro de Patologia e Medicina Laboratorial, 2002
resumo A classificação dos linfomas não-Hodgkin tem sido, ao longo dos últimos trinta anos, motiv... more resumo A classificação dos linfomas não-Hodgkin tem sido, ao longo dos últimos trinta anos, motivo de controvérsia. Várias classificações têm sido propostas em busca de um consenso entre patologistas e clínicos. Este trabalho teve como objetivo analisar ...
Persistent candidemia refers to the continued isolation of the same Candida species in the blood ... more Persistent candidemia refers to the continued isolation of the same Candida species in the blood of a candidemic patient. Its incidence and clinical consequences are not well understood because of the lack of a homogeneous definition for persistent candidemia and the absence of prospective studies in which blood cultures were performed at prespecified times. Data from randomized clinical trials indicate that between 8% and 15% of candidemic patients have persistently positive blood cultures at the end of treatment, and the few studies that have attempted to evaluate the impact of persistent candidemia on outcomes have lacked appropriate analysis to conclude whether persistent candidemia is associated with worse outcome. On the other hand, assuming that it represents therapeutic failure, major causes for persistent candidemia include host factors (probably the most important), drug resistance, low serum levels of drugs, endovascular infection, deep-tissue abscesses, and infection associated with prosthetic material.
... 6. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, et al. ... Correspondence: M... more ... 6. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, et al. ... Correspondence: Marcio Luiz Moore Nucci Rua Professor Rodolpho Paulo Rocco, 255 – 4º andar, sala 4/12 – Ilha do Fundão 21.941-913 – Rio de Janeiro-RJ – Brasil Tel.: (55 21) 2562-2463 E-mail ...
Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare m... more Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare micafungin with liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidosis. We did a double-blind, randomised, multinational non-inferiority study to compare micafungin (100 mg/day) with liposomal amphotericin B (3 mg/kg per day) as first-line treatment of candidaemia and invasive candidosis. The primary endpoint was treatment success, defined as both a clinical and a mycological response at the end of treatment. Primary analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT00106288. 264 individuals were randomly assigned to treatment with micafungin; 267 were randomly assigned to receive liposomal amphotericin B. 202 individuals in the micafungin group and 190 in the liposomal amphotericin B group were included in the per-protocol analyses. Treatment success was observed for 181 (89.6%) patients treated with micafungin and 170 (89.5%) patients treated with liposomal amphotericin B. The difference in proportions, after stratification by neutropenic status at baseline, was 0.7% (95% CI -5.3 to 6.7). Efficacy was independent of the Candida spp and primary site of infection, as well as neutropenic status, APACHE II score, and whether a catheter was removed or replaced during the study. There were fewer treatment-related adverse events--including those that were serious or led to treatment discontinuation--with micafungin than there were with liposomal amphotericin B. Micafungin was as effective as--and caused fewer adverse events than--liposomal amphotericin B as first-line treatment of candidaemia and invasive candidosis.
Invasive fungal diseases (IFDs) represent an important cause of treatment failure in adults with ... more Invasive fungal diseases (IFDs) represent an important cause of treatment failure in adults with acute leukemia. Because of leukemia's heterogeneity, the risk for IFDs is highly variable. We therefore apply a risk-adapted antifungal strategy with strong emphasis on pretreatment and day-15 posttreatment to allow earlier and more individualized interventions. We determine pretreatment risks for IFDs based on 4 factors: (1) host fitness for standard therapy (ie, fit, unfit, or frail); (2) leukemia resistance (high vs low probability of achieving complete remission [CR]); (3) anticipated treatment-related toxicity such as neutropenia, mucositis, and steroid-induced immunosuppression; and (4) patient exposure to opportunistic fungi. Accordingly, we stratify patients as high, intermediate, or low risk for IFDs and apply risk-adapted antifungal strategies, including primary or secondary prophylaxis and diagnostic-based preemptive or empiric therapy. Prevention of IFDs also relies on optimizing organ function, decreasing exposure to opportunistic fungi, and improving net state of immunosuppression with use of better-tolerated and investigational agents for unfit patients and those with adverse leukemia biology. Novel targeted and safe therapies that can achieve higher rates of sustained CR among patients with adverse genetics offer the best promise for reducing the burden of IFDs in these patients.
The management of chronic myeloid leukemia (CML) has changed radically since the introduction of ... more The management of chronic myeloid leukemia (CML) has changed radically since the introduction of imatinib therapy. The decision of whether to offer a patient a hematopoietic stem cell transplant (HSCT) must be based on the probability of success of the procedure. The aim of this retrospective analysis of 1,084 CML patients who received an allogeneic HSCT in 10 Brazilian Centers between February 1983 and March 2003 was to validate the EBMT risk score. The study population comprised 647 (60%) males and 437 (40%) females, with a median age of 32 years old (range 1 - 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1,025 (94%) received an HLA fully matched sibling transplant and only 59 (6%) received an unrelated transplant. In 283 cases (26%) a male recipient received a graft from a female donor. The interval from diagno...
Uploads
Papers by Marcio Nucci