Risk Factors For Invasive Fungal Infections Research Articles

The interaction between piperacillin/tazobactam and assays for Aspergillus galactomannan and 1,3-beta-d-glucan in patients without risk factors for invasive fungal infections

The aim of this study was to investigate the interaction between intravenous piperacillin/tazobactam treatment and Aspergillus galactomannan antigen (GM) and 1,3-beta-D: -glucan (BDG) test results in patients without known risk factors for invasive fungal infections (IFI). Patients without known risk factors for IFI and who were to receive piperacillin/tazobactam monotherapy were considered eligible for the study. Serum samples were obtained both before and after antibiotic infusion on the first, third, seventh and tenth days of a piperacillin/tazobactam treatment course and 4 days after the last dose. GM was determined by Platelia Aspergillus ELISA (Bio-Rad Laboratories) and BDG was assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA) according to manufacturers' specifications. A total of 135 serum samples were collected from 15 patients. When a cut-off level of >or=0.7 was used for GM positivity, there were no false positive results. When a cut-off level of >or=0.5 was used, six serum samples were positive. There were no statistically significant differences between the median GM indices or median BDG levels of the various sampling times. However, 24 of 135 serum samples were positive for BDG for a threshold of 80 pg/mL. After ruling out fungal infections and all known potential causes of false BDG positivity, environmental contamination remained a possible cause of BDG reactivity. No significant interaction was observed between piperacillin/tazobactam administration and Aspergillus GM and BDG assays. Positive results for these tests should be evaluated cautiously in patients at high risk for IFI receiving piperacillin/tazobactam.

Retrospective analysis of invasive fungal infection in surgical intensive care unit

To conduct a retrospective analysis of the invasive fungal infection (IFI) in surgical intensive care unit (SICU). The IFI data of the patients who were admitted in SICU during January 2003 to December 2008 was retrospectively analyzed. A total of 3743 patients were admitted into SICU. Among them, 271 patient's SICU duration was more than 48 hours, who had fungi examination. Seventy-five patients were diagnosed IFI, the morbidity was 2.00% (75/3743), the incidence of fungemia was 0.27% (10/3743), the mortality of IFI patients was 49.33% (37/75). The morbidity rate of each year was almost the same. The mortality of 2007 and 2008 was higher than before (both P < 0.05). Thirty-four of all the 75 IFI patients got urinary tract infected, 37 got fungal pneumonia, 10 got fungemia, 1 got catheter-related fungal infection, 2 got fungal infection in abdomen, 2 got biliary tract infected. Eighty-six fungi strains which caused fungal infection were spotted. Candida albicans was the most common isolate (46.51%). Other isolates were Candida glabrata (22.09%), Candida tropicalis (13.95%), Candida parapsilosis (8.14%), Candida krusei (3.49%), Trichosporon (4.65%), Aspergillus (1.16%). Assist ventilation, combination of bacterial infection, treatment by broad spectrum antibiotics or more than three kinds of antibiotics were the most important risk factors of IFI in SICU. Prophylactic antifungal treatment may be useful. The morbidity of IFI in our SICU was comparatively low, and the same of the incidence of fungemia. The mortality of IFI patients was markedly high. The main sites of infection were lung and urinary tract, and the pathogenic fungi strains were mostly Candidas. Assist ventilation, combination of bacterial infection, broad spectrum antibiotics treatment were the most important risk factors of IFI in SICU.

Primary Antifungal Prophylaxis in Adult Hematopoietic Stem Cell Transplant Recipients: Current Therapeutic Concepts

In recipients of hematopoietic stem cell transplants (HSCTs), the mortality associated with invasive fungal infections (IFIs) remains high, despite the introduction of broad-spectrum antifungal agents over the past 2 decades. Preventing exposure to fungal pathogens in this population is impossible; therefore, clinicians have focused on prophylactic use of antifungal agents to prevent IFIs in high-risk HSCT recipients. It is important to target antifungal prophylaxis by type of HSCT (autologous or allogeneic), local epidemiology, and risk factors for IFIs so that patients can receive the most appropriate agent while balancing costs and the risks of toxicity, and minimizing the development of resistance. To assist clinicians in weighing the pros and cons of currently available antifungal agents when choosing a suitable prophylactic regimen, we provide a review of several key prospective randomized trials that evaluated various antifungal agents for primary prophylaxis in adult HSCT recipients. In addition, we describe the epidemiology of and risk factors for IFIs in HSCT recipients, the difficulties in diagnosing IFIs, antifungal agents used for prophylaxis, and the goals of primary prophylaxis. Fluconazole remains the gold standard for primary prophylaxis in autologous HSCT recipients. For allogeneic HSCT recipients, the agent chosen for prophylaxis must be based on the patient's risk factors for IFIs. In low-risk patients, fluconazole is an appropriate agent to use for primary prophylaxis immediately after transplantation. However, in allogeneic HSCT recipients who develop complications, such as graft failure, graft-versus-host disease, or cytomegalovirus infection, prophylaxis with a mould-active agent should be used.

Approaches to the Management of Invasive Fungal Infections in Hematologic Malignancy and Hematopoietic Cell Transplantation

Patients with hematologic malignancy and hematopoietic cell transplant (HCT) recipients are at increased risk for invasive fungal infection (IFI) as a result of immunosuppression or organ damage stemming from their underlying disease, its treatment, or both. Such IFIs can cause significant morbidity and mortality, and the diagnosis and treatment of infected patients frequently are clinically challenging. This article discusses the epidemiology and risk factors for IFI in patients with hematologic malignancy and HCT recipients. The pros and cons of available antifungal agents are discussed, and evolving treatment strategies and recent prophylaxis guidelines from various professional organizations are reviewed. Finally, recommendations are offered for antifungal prophylaxis according to risk group.

Current Approaches in Antifungal Prophylaxis in High Risk Hematologic Malignancy and Hematopoietic Stem Cell Transplant Patients

Invasive fungal infections (IFIs) pose the most serious infectious risk to patients with hematologic malignancies and in those undergoing hematopoietic stem cell transplantation (HSCT). Invasive candidiasis has an incidence of 8-18% and a mortality of 30-40% in various reports. Invasive aspergillosis has an incidence of 4-15% and an even higher mortality of 60-85% cited in the published literature. IFIs have remained difficult to diagnose in a timely way in neutropenic and immunocompromised patients. A timely diagnosis is essential in promptly initiating antifungal therapy in order to optimize clinical outcomes. Thus, antifungal prophylaxis has an enormous appeal to minimize the threat from IFIs. In this article, the epidemiology and risk factors for IFIs as well as evidence from antifungal prophylaxis clinical trials in certain patient groups with hematologic malignancies are reviewed. Antifungal prophylaxis has been shown to be effective in certain settings. However, concerns about shifts in fungal epidemiology, emergence of resistance, drug toxicities, and drug interactions must be considered in deciding how and in whom to use antifungal prophylaxis.

Candida colonization and invasive fungal infection in hospitalized patients with hematological malignancies

To investigate thee status of Candida colonization and the risk factors of invasive fungal infection (IFI) in hospitalized patients with hematological malignancies. 114 patients with hematological malignancies admitted to the hematology wards from May 2004 to April 2005 underwent fungal culture of their samples of urine, feces, and saliva once a week until the end of the sixth week of hospitalization or they were discharged. Culture of blood, sputum, or sterile body fluids were carried out when the patients were suspected to have IFI. 165 strains of Candida spp. were isolated from 46 of the 114 patients, C. albicans accounting for 78.8% and non-albicans Candida for 21.2% respectively. Candida was found in 38 patients (33.3%) were found to have colonization of Candida, chiefly C. albicans (76.3%). The risk factors of Candida colonization included long duration of leucopenia (WBC < 0.5 x 10(9)/L for more than 10 days) and broad-spectrum antibiotic administration. Univariate analysis showed that the risk factors of IFI included Candida colonization, long duration of leucopenia, and administration of carbapenem antibiotics, and multivariate analysis showed that long duration of leucopenia (WBC < 0.5 x 10(9)/L for more than 10 days) was the only risk factor of IFI (P = 0.015). C. albicans is still the major organism isolated from the patients with hematological malignancies. Patients with hematological malignancies have a high incidence of Candida colonization. Long duration of leucopenia is the only risk factor for IFI.

The Clinical Feature of Invasive Fungal Infection in Pediatric Patients With Hematologic and Malignant Diseases

Invasive fungal infections (IFI) are an important complication in hematologic malignancies and stem-cell transplantation (SCT). However, there are limited data characterizing IFI in children. The clinical feature of IFI after chemotherapy and SCT were analyzed in 334 pediatric patients treated at Hokkaido University Hospital from 1997 to 2006. The cumulative incidence of IFI was 6.9%; this comprised cases of proven, probable and possible IFI at rates of 1.2%, 3.0%, and 2.7%, respectively. The infected lesions were lung in 14 patients, liver in 5 patients, brain in 3 patients, fungemia in 2 patients, kidney in 1 patient, and endophthalmitis in 1 patient. The mortality of IFI was 48.2%, excluding patients who died due to relapse and interstitial pneumonitis; in particular, 71.4% patients with a lung lesion (10/14) died due to IFI. Fifty-nine pediatric patients died in our institution over the 10-year period of the study and IFI was the direct cause of death in 18.6% (11/59) of the patients. Risk factors for IFI with chemotherapy and SCT were also analyzed. Univariate analysis showed that age at diagnosis older than 10 years, relapse of original disease, long-term administration of broad-spectrum antibiotics, and acute myelogenous leukemia (AML) were the risk factors for IFI. All patients with IFI received long-term antibiotic therapy. AML was most strongly associated using a multivariate analysis. The prognosis of IFI has been expected poor; therefore, prevention of this condition, especially for older patients with AML, would be important.

Prophylaxis, pre-emptive or empirical antifungal therapy: which is best in non-lung transplant recipients?

Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following solid organ transplantation (SOT) are relatively common owing to the transplant recipient's overall immunosuppressed status. The incidence of invasive mycoses following SOT ranges from 5% to 42% depending on the organ transplanted. Moreover, invasive fungal infections (IFIs) account for significant morbidity and mortality in SOT, ranging between 25% and 95% depending on the type of fungus and its organ localisation. The frequency, incidence and clinicoepidemiological characteristics of IFIs in patients who are recipients of non-pulmonary solid organ transplantation (NP-SOT) are very different from those that occur in patients with lung transplantation and haematopoietic stem cell transplantation. Candida and Aspergillus spp. are the cause of most infections. These fungal infections are associated with high overall mortality rates. Different strategies (prophylaxis, pre-emptive treatment, empirical therapy, antifungal combinations, routes of administration) have been tested to improve the prognosis of these invasive mycoses in SOT. To achieve this objective it is essential to have new antifungal drugs with a higher spectrum of activity against the fungal pathogens, both classical and emerging, and showing improvements in pharmacokinetic and pharmacodynamic characteristics, ease of administration and acceptability, and lower rates of adverse effects. This article will review the risk factors for IFIs in NP-SOT recipients and the available antifungal strategies for management. In addition, it will evaluate the role of prophylactic therapy in this group of patients.

Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients

IntroductionFungal infection is increasingly common in critical illness with severe sepsis, but the influence of invasive fungal infection (IFI) on severe sepsis is not well understood. The aim of this study was to investigate the impact that IFI has on the outcomes of critically ill surgical patients with severe sepsis in China by means of matched cohort analysis; we also evaluated the epidemiologic characteristics of IFI in this population.MethodsRecords for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis.ResultsA total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both Gram-positive and Gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P < 0.001), high hospital costs (P = 0.038), and prolonged stay in the ICU (P < 0.001) and hospital (P = 0.020).ConclusionIFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources.

Fungal and Bacterial Infections in Acute Myeloid Leukemia Patients Treated with Induction Regimens Including Fludarabine: A Retrospective Analysis of 224 Cases.

Infections are the major cause of morbidity and mortality of acute myeloid leukemia (AML). Invasive Fungal Infections (IFIs) occur in at least 10 to 20% of the patients submitted to induction and consolidation treatments, are responsible for death during induction in up to the 5% of the cases and may cause a delay in consolidation and intensification therapy. Among the risk factors for IFIs it has been included the use of Fludarabine (Fluda), which can induce severe and prolonged immunosuppression. In this study we retrospectively analyzed the infections occurred in 224 newly diagnosed AML patients, aged at least 65 years, consecutively treated with an induction regimen including Fluda, Ara-C and idarubicine with or without etoposide (FLAI/FLAIE). During induction phase, 181/224 (81%) patients experienced a fever of undetermined origin (FUO), the incidence of Gram negative and positive sepsis was 16% (37/224) and 29% (65/224) respectively and 7/224 (3%) patients developed a possible/probable IFI. In 6/224 patients (3%) a proven IFI was found (4 aspergillosis and 2 candidiasis). We then collected the data of the incidence of infections during the first consolidation course (FLAI: n=70; high-dose Ara-C [HD-AC]: n=65; idarubicine and HD-AC: n=89). The overall incidence of FUO was 34% (76/224), the number of Gram negative and positive sepsis was 52/224 (23%) and 49/224 (22%), respectively and 2/224 (1%) patients developed a proven IFI (3 aspergillosis and 1 candidiasis). We subsequently evaluated the incidence of infections in the three different consolidation groups. No significant differences were observed in terms of FUO, Gram positive and negative bacteraemia/sepsis and possible, probable and proven IFIs, during consolidation with Fluda-based regimen and with HD-AC-based regimens. Interestingly, the overall incidence of IFIs during consolidation with FLAI was significantly lower than during consolidation with HD-AC-based treatment program (0% vs 9%; p=0.02). These data, even though retrospectively collected, suggest that Fluda-based chemotherapy is not followed by increased incidence of infections, in particular IFIs, in comparison with conventional non-Fluda based regimens commonly used for AML induction. In our series, Fluda-based consolidation chemotherapy caused a significantly lower incidence of IFIs compared to HD-AC-based consolidation. This may be related to the lower duration of neutropoenia in patients treated with FLAI with respect to those treated with HD-AC/HD-AC + idarubicine.

Evaluation of Risk Factors for Invasive Fungal Infection After Allogeneic Stem Cell Transplantation in Pediatric Patients

Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality after stem cell transplantation (SCT). The incidence, outcome, and risk factors for IFI after allogeneic SCT were analyzed in 149 pediatric patients treated at Hokkaido University hospital from 1988 to 2006. The cumulative incidence of IFI after allogeneic SCT was 8.1%; this comprised cases of proven, probable, and possible IFI at rates of 0.7%, 4.0%, and 3.4%, respectively. Only 1 patient complicated with IFI in the 100 days after SCT, excluding cases with rejection. Antifungal drugs were effective in 3 of the 12 patients with IFI, but the other 9 patients died because of IFI and relapse of original diseases. Nonrelapse mortality was markedly higher for patients with IFI than for those without IFI (60.0% vs. 20.0%, P=0.0204). Univariate analysis showed that age at transplant, chronic graft-versus-host disease (GVHD), and a corticosteroid dose >2 mg/kg or 60 mg/d for 10 days or longer were possible risk factors for IFI. Of these factors, chronic GVHD was the only factor associated with IFI in a multivariate analysis. Treatment of IFI is very difficult and, therefore, prevention of this condition is important, especially upon occurrence of chronic GVHD.

Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies

Patients with hematologic malignancies are at substantial risk of developing invasive fungal infections (IFI) that are associated with substantial morbidity and mortality. This article reviews the epidemiology, risk factors, and efficacy of antifungal prophylaxis in patients with hematologic malignancies. A PubMed search was conducted to identify relevant studies with special emphasis on meta-analyses and direct comparisons between antifungal agents. The epidemiology of IFI has changed substantially in recent years with Candida albicans becoming less common owing to the widespread prophylactic use of azole antifungals. Invasive aspergillosis, fusariosis, and zygomycosis have increased in frequency. This change is at least partly related to the use of broad-spectrum antifungal agents, either as prophylaxis or as empirical treatment. Other risk factors for IFI include prior fungal exposure, immunosuppression, underlying disease, graft-vs.-host disease, and organ dysfunction. Inconsistent results have been reported in studies evaluating the efficacy of antifungal prophylaxis in patients at risk of IFI. Meta-analyses found that antifungals, such as fluconazole and itraconazole, are effective in decreasing IFI and IFI-related mortality, primarily owing to yeast infections in patients with more severe immunosuppression (i.e. patients undergoing bone marrow transplantation), but do not decrease the overall mortality. The European Conference on Infections in Leukemia (ECIL) guidelines currently recommend fluconazole (AI, ie. strongly recommended, based on at least 1 well-executed, randomized trial) and itraconazole (BI, ie. generally recommended, based on at least 1 well-executed, randomized trial) in allogeneic transplant recipients. Posaconazole, a triazole antifungal, has been recently shown to decrease IFI incidence and overall mortality in some high-risk patients compared with standard azoles. Based on preliminary data, a provisional AI ECIL recommendation has been given. Because of the substantial morbidity and mortality associated with IFI, there is a need to accurately define patient groups at greatest risk of IFI and, when appropriate, to initiate effective antifungal prophylaxis.

Generation and Functional Characterization of T Cells Against Candida albicans as Potential Immunotherapy after Allogeneic Stem Cell Transplantation.

Invasive fungal infections (IFI), in particular infections due to Aspergillus spp and Candida spp, still pose considerable problems in patients undergoing allogeneic stem cell transplantation (SCT). Despite the availability of new antifungal agents, morbidity and mortality of IFI are still unacceptable high. Although neutropenia is known as the single most important risk factor for IFI, there is a growing body of evidence that T cells play a major role in the defense against fungi. Therefore, adoptive immunotherapy with T cells against Candida spp. might be an interesting therapeutic option in patients undergoing allogeneic SCT. After overnight incubation of 1×108 peripheral blood mononuclear cells from 4 healthy individuals with cellular extracts of C.albicans, activated T cells were selected using the IFN-γ secretion-assay (Miltenyi Biotec, Bergisch Gladbach, Germany). After 14 days of culture, T cell clones were generated by limiting dilution and incubated for another 14 days. The median number of cells obtained was 2.6×107 (range, 0.85–5.75×107). Flow cytometry revealed a highly homogenous population of CD3+CD4+ cells (97.2% ± 2.6; n=6), of which an average of 8.6% (range, 4.8–58.2%) produced IFN-gamma on re-stimulation with C.albicans antigens, as assessed by intracellular cytokine staining assay. 20.5% (range, 5.8–72.4%) of the generated cells produced TNF-alpha, whereas no significant number of cells produced TH2 cytokines such as IL-4 and IL-10, indicating that the generated T cell clones were TH1 cells. The percentage of IFN-gamma producing T cells was significant upon stimulation with C.albicans and C.tropicalis, whereas less than 1% of cells produced IFN-gamma upon stimulation with antigens of other yeasts such as C.glabrata, Debaryomyces hansenii and Kluyveromyces lactis and molds such as A.fumigatus, Penicillium chrysogenum and Alternaria alternata. Compared to CD4+ T cells of the original fraction, the isolated and expanded anti-Candida T cells showed reduced alloreactivity, as assessed by means of CSFE. In addition, a strong proliferation of the generated anti-Candida T cells was seen after re-stimulation with C.albicans antigens. The potency of the generated T-cells to damage C.albicans was evaluated using the XTT assay. Compared to polymorphonucelar cells (PMNs), APCs and T-cells alone or to the combination of PMNs with T cells or APCs, respectively, the combination of PMNs, APCs and T-cells showed highest fungal damage (n=4).In conclusion, our data suggest that the isolation and expansion of anti-Candida T cells is possible and feasible. The generated T cells show low alloreactivity in vitro and increase the antimycotic potential of phagocytes. Thus, antimycotic T cells might become an important tool in the prophylaxis and therapy of IFI in patients after allogeneic SCT.

Delayed ABLC prophylaxis after allogeneic stem‐cell transplantation

Invasive fungal infections (IFI) are frequent causes of mortality after allogeneic stem-cell transplantation (SCT). A very important risk factor for IFI is the use of steroids. We used a risk-based chemoprevention in an open-labelled pilot study. All patients received oral fluconazole or itraconazole (200-400 mg day(-1)) during their neutropenic episode. Starting on day +30, patients receiving prednisone > or =30 mg day(-1) were switched to twice weekly Amphotericin-B-lipid-complex (ABLC) in a dose of 4 mg kg(-1). Patients receiving lower steroid doses continued on the fluconazole/itraconazole prophylaxis. Between 1999 and 2002, 100 patients were enrolled and followed for IFI for 1 year. Seven patients were started on therapeutic daily ABLC treatment before day +30 because of documented or suspected IFI; four had definite or probable aspergillosis, and two had candidaemia. Thirty patients did not need prophylactic ABLC; only one developed candidaemia. Sixty-three patients received ABLC prophylaxis for a median of 52 days (range: 1-289). Seven of these patients developed IFI; one definite and two probable cases of aspergillosis, one case of probable Trichosporon beigelii infection, and three cases of candidaemia. The twice weekly ABLC was well tolerated. This risk-based chemoprevention appears to be effective and might diminish the role of steroids as risk factor for IFI after allogeneic SCT. The relatively high incidence of early IFI suggests that additional prophylaxis for IFI may be indicated for poor-risk patients prior to day +30.

Fungal infections in bone marrow transplant recipients

Invasive fungal infections (IFIs) can cause significant morbidity and mortality in patients after haematopoietic stem cell transplantation. The two most notorious pathogenic fungal species in this group of patients are Candida and Aspergillus. Risk factors for IFIs include: prolonged neutropaenia; fungal overgrowth and conditioning regiment-related mucositis; graft versus host disease; and steroid therapy. Clinical manifestations can be protean, and radiological changes are frequently nonspecific. Diagnostic methods include culture- and nonculture-based techniques. Some experts recommend IFI prophylaxis in the high-risk groups, such as patients with severe graft versus host disease who require prolonged immunosuppressive therapy or patients with a previous history of aspergillosis. Treatment options include therapy with azoles, including the newer agent voriconazole, amphotericin and caspofungin.

Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation

Invasive fungal infections (IFI) are the leading cause of infectious mortality in adult patients undergoing hematopoietic cell transplantation (HCT) after myeloablative conditioning, but the extent of this problem in the pediatric population is unclear. We retrospectively examined risk factors for IFI among 120 consecutive pediatric patients undergoing allogeneic HCT at a single center. The incidence of proven or probable IFI in pediatric patients during the first year after allogeneic HCT was 13%, comparable to the rate reported in adult patients; however, unlike IFI in adult patients, the majority of IFI in children occurred within the first month after transplantation. The primary risk factors for IFI were duration of neutropenia, age greater than 10 years, transplant for severe aplastic anemia or Fanconi anemia, and high-dose corticosteroid administration for 10 days or longer. IFI were more likely to be successfully treated (42%, 5/12 patients) in pediatric HCT recipients when compared to previous reports of adult recipients. Nonrelapse mortality was estimated at 17% (20/120 patients) after allogeneic HCT, of which 35% (seven patients) were directly attributed to IFI. Thus, IFI is a significant cause of nonrelapse mortality in children undergoing allogeneic HCT and more effective strategies are needed to prevent and treat IFI.

Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients.

Invasive fungal infections (IFI) are associated with high mortality in liver transplant recipients. Prevention remains an elusive goal, especially for IFI caused by moulds. From January 1998, patients who fulfilled four or more variables identified as risk factors for IFI received a cumulative dose of 1-1.5 g of lipid formulations of amphotericin B (L-AmpB; AmBisome or Abelcet). The development of IFI in these patients was compared with historical patients. Two hundred and eighty liver transplant recipients were analysed over a period of 8 years. In the historical group, IFI were observed in 22 of 131 patients (17%) and invasive aspergillosis in 13 of them (10%). After January 1998, IFI were observed in nine of 149 (6%) (P < 0.01) and invasive aspergillosis in six patients (4%) (P = 0.08). In patients with four or more risk factors (high risk) for IFI, the administration of L-AmpB reduced the risk from 36% to 14% (P = 0.07), and the risk of aspergillosis from 23% to 5% (P = 0.08). Notably, prophylaxis reduced the risk of aspergillosis from 32% to 0% in dialysed patients (P = 0.03). Variables independently associated with IFI in high-risk patients were dialysis [odds ratio (OR) 3.9; 95% confidence interval (CI) 1-16.7] and surgical reintervention (OR 5.4; 95% CI 1.2-24.6), while L-AmpB was a protective factor in this multivariate analysis (OR 0.1; 95% CI 0.02-0.8). The analysis in these high-risk patients was not able to demonstrate an association between the administration of L-AmpB and higher survival. Selected risk factors are good predictors of IFI in liver transplant recipients. The administration of L-AmpB in high-risk patients is independently associated with a reduction of IFI.

Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients.

In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 were retrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. Better prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk of IFI after allogeneic BMT.

The effects of antifungal chemoprophylaxis and empiric therapy on invasive fungal infection in neutropenic children with malignant neoplasms.

Since January 1987, chemoprophylaxis and empiric therapy with antifungal drugs have been used routinely in neutropenic children with neoplasms. The incidence of terminal invasive fungal infection (IFI) diagnosed by autopsy findings is compared in two groups: group A, consisting of 25 patients autopsied between January 1982 and December 1986, and group B, consisting of 14 patients autopsied between January 1987 and December 1991. There was no difference in the incidence of IFI between the two groups, but the characteristics of IFI appeared to differ. With the recent intensification of chemotherapy, the patients in group B had more risk factors for IFI. It might therefore have been anticipated that group B patients may have shown an increase in IFI. No such increase was observed, suggesting that the prophylaxis was effective. Autopsy findings also showed that the target organs of IFI were localized and that systemic candidiasis was decreased in group B. It is thus concluded that the present antifungal countermeasures are effective, although some problems still remain.