Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial.

We performed a prospective, randomized, multicenter trial to evaluate the effectiveness of prophylactic inhalations with aerosolized amphotericin B (aeroAmB) to reduce the incidence of invasive aspergillus (IA) infections in patients after chemotherapy or autologous bone marrow transplantation and an expected duration of neutropenia of at least 10 days. From March 1993 until April 1996, 382 patients with leukemias, relapsed high-grade non-Hodgkin lymphomas, or solid tumors were randomized with a 13:10 ratio to receive either prophylactic aeroAmB inhalations at a dose of 10 mg twice daily or no inhalation prophylaxis in an unblinded fashion. The incidence of proven, probable, or possible IA infections was 10 of 227 (4%) in patients who received prophylactic aeroAmB. This did not differ significantly from the 11 of 155 (7%) incidence in patients who received no inhalation prophylaxis (P =.37). Moreover, no differences in the overall mortality (13% v 10%; P =.37) or in the infection-related mortality (8% v 7%; P =.79) were found. In contrast to other nonrandomized trials, we observed no benefit from prophylactic aeroAmB inhalations, but the overall incidence of IA infections was low.     

Low incidence of invasive aspergillosis in allogeneic stem cell transplant recipients receiving amphotericin B inhalation prophylaxis

A. Nihtinen, V.‐J. Anttila, T. Ruutu, E. Juvonen, L. Volin. Low incidence of invasive aspergillosis in allogeneic stem cell transplant recipients receiving amphotericin B inhalation prophylaxis.
Transpl Infect Dis 2011. All rights reserved Abstract: In this retrospective study we evaluated the impact of amphotericin B (AmB) deoxycholate inhalation prophylaxis on invasive aspergillosis (IA) in 611 allogeneic stem cell transplant (alloSCT) recipients and their tolerance of the inhalations. The inhalations were not used in 1996–2000 (Period I). In 2001–2005 (Period II) all patients with acute graft‐versus‐host disease treated with high‐dose methylprednisolone used the inhalation prophylaxis with a dose of 25 mg daily. No systemic antifungal prophylaxis was routinely used during the study period. IA was detected in 17 (13 proven, 4 probable) out of 257 (6.6%) patients transplanted in Period I and in 9 (6 proven, 3 probable) out of 354 (2.5%) patients transplanted in Period II (P=0.007). The median time to the diagnosis of IA was 95 days and 155 days post transplant in the 2 periods (P=0.225). The mortality of the patients with IA was 94.1% and 66.6% in Period I and Period II. The median duration of AmB inhalation prophylaxis was 84 days. Breakthrough IA was detected in 1 of the 111 (1%) patients during the prophylaxis. No discontinuation of prophylaxis due to side effects was recorded. Overall, with a median follow‐up of 3.5 and 4.6 years, 42.4% and 59% of the patients were alive in Period I and Period II, respectively (P=0.001). In conclusion, the incidence of IA fell during the AmB inhalation prophylaxis, and the inhalations were well tolerated. Mortality of patients with IA was high. The overall survival of patients was significantly higher in Period II, indicating the advances made in SCT therapy over the 10‐year period.     

Fungal colonization in neutropenic patients: a randomized study comparing itraconazole solution and amphotericin B solution

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.     

Multicentre,randomized, open‐label study of on‐demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects

Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on‐demand therapy. Male subjects aged 6–65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open‐label, four‐period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on‐demand therapy. In the intent‐to‐treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on‐demand period, the 50 IU kg^?1 twice‐weekly period, and the 100 IU kg^?1 once‐weekly period respectively. Differences in ABR between the first on‐demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg^?1 twice weekly or 100 IU kg^?1 once weekly reduced ABR by 89.4% relative to on‐demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.     

Effectiveness and safety of salmeterol in nonspecialist practice settings

STUDY OBJECTIVES: To evaluate the effectiveness and safety of inhaled salmeterol in patients managed in nonspecialist practice settings. DESIGN: A randomized, double-blind, 6-month, parallel-group study involving 253 centers. SETTING: Primarily nonspecialist practices (n = 232). PATIENTS: A total of 911 subjects (417 men; 494 women) who met American Thoracic Society asthma criteria were enrolled and randomized to treatment with either twice-daily salmeterol aerosol (50 microg; n = 455) or matching placebo twice daily (n = 456). Both groups were allowed to take salbutamol as needed. All subjects were previously treated with anti-inflammatory maintenance therapy that was continued throughout the study. MEASUREMENTS AND RESULTS: The primary outcome variable was the proportion of subjects with serious asthma exacerbations defined as an exacerbation requiring hospitalization, emergency department visit, or use of prednisone during the treatment period. A total of 712 subjects competed the study. There was no significant difference in the proportion of subjects experiencing serious exacerbations between the salmeterol and placebo groups (20.8% vs 20.9%, respectively; p = 0.935; power > 88%). Peak expiratory flow was significantly higher in the salmeterol group (398 L/min vs 386 L/min for placebo; p < 0.01). Median daily use of salbutamol was two inhalations for the salmeterol group and three inhalations for placebo (p < 0.001). The proportion of subjects sleeping through the night was significantly higher in the salmeterol group (74%) as compared to placebo (68%; p = 0.028). CONCLUSIONS: Salmeterol treatment is effective in subjects typically cared for in the primary-care setting and does not increase the frequency of severe exacerbations.     

Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group

Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.     

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

Background

Posaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia.

Design and Methods

The impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs.

Results

Proven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs.

Conclusions

Primary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a “real-life” scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous.     

Low-dose amphotericin for prevention of serious fungal infection following liver transplantation

AIMS: This study advances previously performed clinical studies of antifungal prophylaxis and prospectively evaluates the efficacy of low-dose amphotericin B preparations for the prevention of invasive fungal infection (IFI) in high-risk liver transplant (LT) recipients. METHODS: High-risk LT patients were recruited and randomised to openly receive intravenously either conventional amphotericin B (amB) at a dose of 15 mg daily, or liposomal amphotericin B (amBisome) 50 mg daily. Prophylaxis was continued until discharge from the intensive care unit (ICU), until patient death, or until time of conversion to high-dose amBisome for treatment of suspected or confirmed IFI. RESULTS: During the study period, 360 adult LTs were performed; 132 patients were eligible for 149 recruitment episodes into the trial, and 83 patients were recruited for 92 episodes. Of the 92, 48 patient episodes were randomised to receive amBisome prophylaxis, and 44 to receive amB. IFI was uncommon, diagnosed for 3 patients in the amBisome group, and for 2 in the amB group. Furthermore, Aspergillus was isolated on a single occasion during 92 episodes of prophylaxis. Fungal colonisation scores did not differ significantly between the 2 groups. There was a significant difference in the rates of survival to ICU discharge between the 2 groups (79.6% amBisome vs. 59.5% amB, P=0.038). Renal function measures including creatinine clearance at commencement and conclusion of prophylaxis, and at 12 months post transplant were not statistically different between the 2 groups. CONCLUSION: The use of amphotericin B, liposomal or non-liposomal preparations at low doses, for prophylaxis of IFI in high-risk LT patients, is associated with a low incidence of serious fungal infection. In this randomised study, low-dose amBisome prophylaxis was associated with an increased likelihood of successful discharge from the ICU.     

Addition of cyclosporin-A to chemotherapy in secondary (post-MDS) AML in the elderly. A multicenter randomized trial of the Leukemia Working Group of the Hellenic Society of Hematology

In elderly patients with secondary leukemia, poor therapeutic response and low overall survival have been attributed mainly to age and to the primary resistance of leukemic cells to chemotherapy. Modulation of resistance has been attempted in different studies, but the results have been contradictory. We conducted an open, randomized multicenter clinical trial involving patients more than 60 years old with secondary leukemia preceded by a myelodysplastic syndrome. The induction chemotherapy regimen included idarubicin, cytarabine, and etoposide (group A); randomization involved simultaneous administration of cyclosporin-A per os (group B). Fifty-five patients were evaluated, 26 in group A and 29 in group B. Overall complete remission was achieved in 40% of the patients, 27% vs 52% in groups A and B, respectively (p=0.01). Leukemia-free survival was more favorable in patients who received cyclosporin-A, 12 vs 7 months for groups B and A, respectively (p=0.03). In a follow up period of 30 months, 7 out of 55 patients (13%) were alive, 4 of whom were in complete remission. Five out of the 7 alive patients were randomized in group B and had received cyclosporin-A. Treatment failure was higher in group A [19 of 26 patients (73%)] than in group B with CsA [14 of 29 patients (48%)] (p<0.0001). Treatment-related toxicity/mortality was 13%. Modulation of drug resistance by CsA in elderly people suffering from secondary acute leukemia may improve the outcome of chemotherapy without increasing drug toxicity and treatment-related mortality.     

A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients.

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.     

两性霉素B治疗COPD合并侵袭性肺曲霉菌病的相关性研究

目的对比两性霉素B与伊曲康唑治疗C0PD合并侵袭性肺曲霉菌病(IPA)的临床疗效、不良反应及治疗费用。方法对比研究我院两性霉素B治疗COPD合并IPA的52例患者诊疗过程与伊曲康唑治疗COPD合并IPA的25例患者诊疗过程。结果两性霉素B治疗COPD合并IPA有效率70.2%,不良反应发生率53.1%,主要是低血钾(44.7%),寒战发热(31.9%),中位疗程29天,治疗经费1820元,7例中途放弃治疗(14.9%);伊曲康唑治疗COPD合并IPA有效率68.4%,不良反应发生率10.5%,均为轻度肝功能异常(5.3%),中位疗程26天,治疗经费28000元,6例中途放弃治疗(24%)。结论与伊曲康唑相比,两性霉素B治疗COPD合并IPA疗效肯定,不良反应发生率高,但无严重不良反应,且治疗经费低,患者能坚持治疗,是较为安全有效的一线抗真菌药物。     

Early Bronchodilatory Effects of Budesonide/Formoterol pMDI Compared with Fluticasone/Salmeterol DPI and Albuterol pMDI: 2 Randomized Controlled Trials in Adults with Persistent Asthma Previously Treated with Inhaled Corticosteroids

Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged ≥18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 μ g, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 μ g × 2 inhalations (160/9 μ g), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 μ g × 1 inhalation, albuterol pMDI 90 μ g × 2 inhalations (180 μ g), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV₁) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV₁ within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.     

Disseminated lymphoblastic lymphoma in children and adolescents: results of the COG A5971 trial: a report from the Children's Oncology Group

The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS‐negative Stage III and IV lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin‐Frankfurt‐Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non‐Hodgkin lymphoma/BFM‐95 therapy with high dose MTX in interim maintenance but no IT‐MTX in maintenance (Arm B1) . Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5‐year event‐free survival (EFS) for the four arms: Arm A1 , 80% [95% confidence interval (CI) 67–89%] and Arm A2 , 81% (95% CI 69–89%); Arm B1 , 80% (95% CI 68–88%) and Arm B2 , 84% (95% CI 72–91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly [5‐year EFS of 63% (95% CI 29–85%)]. For CNS‐negative patients, there was no difference in outcome based on CNS prophylaxis (IT‐MTX versus HD‐MTX) or with intensification.     

A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients

Fluconazole antifungal prophylaxis is standard care in allogeneic hematopoietic stem cell transplant (HSCT) recipients, but this drug lacks anti-Aspergillus activity, the primary cause of invasive fungal infection (IFI) in many transplantation centers. We performed a randomized trial to compare itraconazole vs fluconazole, for prevention of IFIs in patients with acute leukemia (AL) and HSCT recipients. One hundred and ninety-five patients were randomly assigned to either fluconazole or itraconazole antifungal prophylaxis, after stratification into high-risk and low-risk groups. Antifungal prophylaxis was started at the beginning of chemotherapy and continued until resolution of neutropenia, or until amphotericin B treatment was started. IFI occurred in 11 (11%) of itraconazole, and in 12 (12%) fluconazole recipients. Invasive candidiasis (IC) developed in two (2%) itraconazole and one (1%) fluconazole recipients, while invasive aspergillosis (IA) developed in nine (9%) itraconazole and 11(11%) fluconazole recipients. There was no difference in the incidence of total IFI, IC and IA between the two study arms. However, there was a nonsignificant trend towards reduced mortality among patients who developed IA while receiving itraconazole prophylaxis (3/9=33% vs 8/11=73%, P=0.095).     

Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia

Summary The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneicn=271, autologousn=27, syngeneicn=5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.     

Comparison of ciprofloxacin with polymyxin B for infection prophylaxis in neutropenic patients with acute non-lymphocytic leukemia

Twenty-four neutropenic patients receiving intensive chemotherapy for acute non-lymphocytic leukemia were studied in a randomized trial comparing ciprofloxacin with polymyxin B for prevention of infections. Both groups (12 patients each group) received amphotericin B for antifungal prophylaxis. 20 febrile episodes occurred in 22 courses of oral prophylactic ciprofloxacin and 22 occurred in 24 courses of oral prophylactic polymyxin B. Patients receiving ciprofloxacin had a mean time to the first infection-related febrile episode of 7.2 days, compared with 4.3 days for the polymyxin B group (p less than 0.01). Patients receiving ciprofloxacin also had fewer days of fever (average 6.5 days versus 9.8 days for the polymyxin B group, p less than 0.02). Duration of administration of parental antibiotics were also shorter in the ciprofloxacin group (p less than 0.001). Although modifications of the empiric antibiotic regimen were required more frequent in patients receiving polymyxin B, this did not reach statistical significance. These results suggest that ciprofloxacin is a more efficacious oral antimicrobial agent than polymyxin B for the prevention of infections in neutropenic patients with acute non-lymphocytic leukemia.     

A randomized study comparing fluconazole with amphotericin B/5-flucytosine for the treatment of systemicCandida infections in intensive care patients

Summary In this prospective, randomized study fluconazole and amphotericin B/5-flucytosine were compared in the treatment of systemic candidiasis. Seventy-two non-neutropenic intensive care patients with systemicCandida infections were enrolled. Thirty-six patients were randomly assigned to receive fluconazole (400 mg on the first day then 200 mg) and 36 were randomized to amphotericin B/5-flucytosine (1.0–1.5 mg/kg body weight every other day and 3×2.5 g flucytosine/day) for 14 days following the diagnosis. There was no statistically significant difference in clinical outcome in regard to the treatment of pneumonia and sepsis: 18/28 of the patients were treated successfully with fluconazole and 17/27 with amphotericin B/5-flucytosine. For the treatment of peritonitis, however, amphotericin B/5-flucytosine was more effective than fluconazole (55% vs. 25%). Furthermore, amphotericin B/5-flucytosine was found to be superior to fluconazole with regard to pathogen eradication (86% vs. 50%). Fluconazole was associated with less toxicity than amphotericin B/5-flucytosine.

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Studie zur Wirksamkeit von Fluconazol im Vergleich zu Amphotericin B/5-Flucytosin bei Intensivpatienten mit systemischen Mykosen

Zusammenfassung In dieser prospektiven, randomisierten Studie wurde die Wirksamkeit von Fluconazol (400 mg am ersten Tag der Therapie, dann 200 mg) gegenüber der Kombination von Amphotericin B/5-Flucytosin (1–1.5 mg/kg Körpergewicht Amphotericin B jeden zweiten Tag und 3×2.5 g 5-Flucytosin/die) verglichen. Es wurden 72 Patienten (36 in die Fluconazol-Gruppe und 36 in die Amphotericin-Gruppe) aufgenommen und mindestens 14 Tage lang nach der Diagnosestellung behandelt. Bei der Behandlung der Sepsis und Pneumonie ergaben sich in beiden Gruppen keine signifikanten Unterschiede in bezug auf die Heilungsrate (63% in der Fluconazol-Gruppe und 64% in der Amphotericin-Gruppe). Bei der Therapie der Peritonitis war Amphotericin B/5-Flucytosin überlegen (55% vs. 25%). Außerdem war unter der Kombinationstherapie die Keimelimination höher (86% vs. 50%). Während der Therapie mit Fluconazol traten weniger oft Nebenwirkungen auf.

     

Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation

Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.     

Topical prophylaxis of conjunctivitis induced by high-dose cytosine arabinoside

We investigated the efficacy of dexamethasone plus diclofenac eye drops as prophylaxis for conjunctivitis induced by high-dose (HD) cytarabine (Ara-C). Sixty patients were randomized to receive either dexamethasone (group A, n=29) or dexamethasone plus diclofenac (group B, n=31). Conjunctivitis was experienced by 13/29 (45%) patients in group A, and 4/31 (13%) patients in group B (p相似文献   

Cytokine profile in lung transplant recipients with Aspergillus spp colonization

We studied cytokine profiles in BAL of LTRs with Aspergillus spp colonization who did not progress to IPA in the absence of antifungal prophylaxis. This was a retrospective, single center case‐control study. BAL samples were analyzed for cytokines. Patients with Aspergillus spp in BAL who did not receive prophylaxis and did not develop IPA were compared to LTRs with Aspergillus spp that received prophylaxis, LTRs with IPA and controls. Twenty‐one patients with Aspergillus colonization who did not develop IPA, seven patients with suspected IPA who received prophylaxis, 4 IPA and 19 controls were included. IPA group had significantly higher levels (median [IQR]) of MIP‐1 beta compared to the Suspected IPA group (5 vs 5 P: 0.03). The Suspected IPA group had significantly higher levels of IL‐12 (11.38 vs 1 P: 0.0001), IL‐1 RA (86.11 vs 23.98 P: 0.0118), IP‐10 (22.47 vs 0.86 P: 0.0151), HGF (40.92 vs 16.82 P: 0.0055), and MIG (169.62 vs 5 P: 0.0005) than Colonization group. We have identified a unique cytokine signature in patients with Aspergillus colonization that do not develop IPA. Our study forms basis for a larger study to use these cytokines profile to identify patients at a lower risk of developing IPA.