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B E de Pauw

Publications and source records attributed to B E de Pauw.

At least 19 recordsLinked to original sources
PubMed2006

Impact of alternate definitions of fever resolution on the composite endpoint in clinical trials of empirical antifungal therapy for neutropenic patients with persistent fever: analysis of results from the Caspofungin Empirical Therapy Study.

BACKGROUND: Sensitivity analyses were incorporated in a Phase III study of caspofungin vs. liposomal amphotericin B as empirical antifungal therapy for febrile neutropenic patients to determine the impact of varying definitions of fever resolution on response rates. METHODS: The primary analysis used a 5-part composite endpoint: resolution of any baseline invasive fungal infection, no breakthrough invasive fungal infection, survival, no premature discontinuation of study drug, and fever resolution for 48 h during the period of neutropenia. Pre-specified analyses used 3 other definitions for fever resolution: afebrile for 24 h during the period of neutropenia, afebrile at 7 days post therapy, and eliminating fever resolution altogether from the composite endpoint. Patients were stratified on entry by use of antifungal prophylaxis and risk of infection. Allogeneic hematopoietic stem cell transplants or relapsed acute leukemia defined high-risk patients. RESULTS: In the primary analysis, 41% of patients in each treatment group met the fever-resolution criteria. Low-risk patients had shorter durations of neutropenia but failed fever-resolution criteria more often than high-risk patients. In each exploratory analysis, response rates increased in both treatment groups compared to the primary analysis, particularly in low-risk patients. CONCLUSIONS: Response rates for the primary composite endpoint for both treatment groups in this study were driven by low rates of fever resolution. Requiring fever resolution during neutropenia in a composite endpoint can mask more clinically relevant outcomes.

Adolescent↗
PubMed2005

[Improved diagnostics in invasive aspergillosis and systematic monitoring in patients at high risk of infection].

Invasive aspergillosis remains an important cause of morbidity and mortality in patients with prolonged and severe immune suppression such as following haematopoietic stem-cell transplantation. Consensus definitions, which allow categorisation of patients based on diagnostic criteria, are an important improvement in uniform registration of invasive mycoses in clinical trials. Prospective monitoring of high-risk patients for the circulating aspergillus cell-wall component galactomannan, results in earlier diagnosis in two-thirds of patients when compared with conventional diagnostic methods. High-resolution CT (HRCT) enables the lesions characteristic of invasive mycoses to be detected earlier and better than by chest radiograph. In addition, invasive mycoses cause characteristic lesions on the HRCT scan including the halo-sign and the air-crescent sign. The pre-emptive management strategy which combines monitoring of patients for surrogate markers with a HRCT scan appears to be a promising approach to the early identification and treatment of patients with invasive aspergillosis.

Aspergillosis↗
PubMed2005

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant.

We determined gut mucosal barrier injury (MBI) among 129 recipients of an allogeneic or autologous haematopoietic stem cell transplant (HSCT) who had been given different myeloablative regimens by measuring integrity using the lactulose/rhamnose (RHA) ratio and absorption using the ratios of rhamnose/3-O-methylglucose and xylose/3-O-methylglucose. Regimens that did not contain idarubicin induced oral mucositis and disturbed gut integrity and absorption earlier than did those containing the anthracycline. By contrast, regimens containing idarubicin induced more severe and prolonged oral and gut MBI. Gut integrity and absorption of most patients were still abnormal at discharge from hospital. These results confirm that the integrity and absorptive capacity of the gut is affected adversely by myeloablative regimens in general, although only two patterns of mucosal injury emerged depending on whether or not idarubicin was used.

Adult↗
PubMed2004

Measuring mucosal damage induced by cytotoxic therapy.

We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnosed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Gut integrity was already disturbed in the AML/MDS group as measured by the lactulose/rhamnose ratio (L/R ratio=0.09) before therapy and was severely perturbed (L/R ratio >0.13) for a month after HSCT. Oral mucositis and to a lesser extent gut toxicity was only significantly correlated with disturbed permeability in the transplant group. The data suggest that sugar permeability, oral mucositis and gut toxicity measure different features of mucosal damage after intensive cytotoxic therapy.

3-O-Methylglucose↗
PubMed2004

An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis.

Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.

Adolescent↗
PubMed2003

Feasibility of a new in vitro approach to evaluate cellular damage following co-infusion of red blood cell concentrates and intravenous drug solutions.

INTRODUCTION: Transfusion guidelines may result in unwanted delay in infusion schemes, as simultaneous infusion of blood components and drug solutions is universally prohibited. The aim of this study was to measure possible damage to red cells by drug solutions, as manifested by haemolysis, using a dynamic model that resembles the clinical setting. METHODS: Stored filtered and irradiated RBC concentrates and drug solutions were co-infused in an in vitro dynamic model. Also, incubation in a static model was performed. The haemolytic potency of the drug solutions was measured by determining free haemoglobin (fHb) levels. RESULTS AND DISCUSSION: Neither in the dynamic tests nor in the static tests did fHb levels exceed the maximally acceptable standard for filtered RBC concentrates according to Dutch specification guidelines. In the static test model, fHb levels were slightly elevated compared with those of control samples, as well as those in the dynamic test model. CONCLUSION: A novel in vitro dynamic infusion system appears to represent a useful technique to calculate possible damage to RBCs resulting from co-infused drug solutions. Co-infusion of the drug solutions tested with filtered and irradiated RBC concentrates did not produce fHb levels above the levels accepted by the Dutch national guidelines. Apart from haemolysis, other parameters reflecting RBC damage should be investigated in future studies.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2002

Achievements and goals of the EORTC Invasive Fungal Infections Group. European Organisation for Research and Treatment of Cancer.

Invasive fungal infections are an increasing complication for patients with cancer. These infections still are difficult to diagnose and to treat and thus still have a high fatality rate. New strategies should include evaluation of new diagnosis tools and large-scale assessment of these new methods will need multidisciplinary collaboration. High-quality clinical trials dedicated to establish 'state-of-the-art' prevention and treatment are also directly needed. Created in 1991, the EORTC Invasive Fungal Infection Group has faced several of these challenges and significantly improved the knowledge and management of these infections in Europe.

Antifungal Agents↗
PubMed2001

Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

Antifungal Agents↗
PubMed2001

Empirical therapy of febrile neutropenic patients with mucositis: challenge of risk-based therapy.

Nowadays Gram-positive cocci, especially oral viridans streptococci (OVS) and coagulase-negative staphylococci (CoNS), are the most common bloodstream isolates in febrile neutropenic patients. Although in general these cocci are quite indolent, Streptococcus mitis is associated with serious complications such as sepsis and/or adult respiratory distress syndrome. Neutropenia is the most significant predisposing factor but the impact of mucositis, i.e. damage to the mucosal barrier of mouth and intestines (mucosal barrier injury, MBI), is very much greatly underestimated. Oral mucositis is a strong predictor of OVS bacteremia and simultaneously CoNS bacteremia is clearly associated with mucositis. Treatment with especially high dose cytarabine, cyclophosphamide and idarubicin, when given to allogeneic hematopoietic stem cell transplant recipients, predictably results in mucositis. Hence, the occurrence of mucositis should have implications for complementing empirical therapy with specific drugs such as glycopeptides, because risk patients can be selected based upon the chemotherapeutic therapy administered. An algorithm is presented for dealing with patients at high risk of mucositis and bacteremia due to Gram-positive cocci.

Anti-Bacterial Agents↗
PubMed2001

Reliability of clinical research on invasive fungal infections: a systematic review of the literature.

The aim of this study was to assess the comparability and reliability of clinical research on invasive fungal infections (IFIs) which is accumulating in the medical literature. A Medline search strategy was developed covering the years 1985-1997. The 7,086 articles identified this way were further limited to 173 by reading the abstracts to studies involving immunocompromised patients and deep tissue infections. Diagnostic criteria used for definitions of IFIs were evaluated according to the level of confidence in diagnosis. For analysing the reliability, we used the sample of 397 patients from the European Organization for Research and Treatment of Cancer (EORTC) database. Each patient in the database was evaluated according to the definitions employed in each article. The level of overall agreement among the articles was very low (Kappa = 0.253). The results of this analysis show the discrepancy in the medical literature in diagnosing IFIs and the necessity for the standardization of definitions.

Antifungal Agents↗
PubMed2000

Prophylaxis and treatment of fungal infections associated with haematological malignancies.

Patients with haematological malignancies form one of the most susceptible host groups for microbial infection, especially during neutropenia. The incidence of invasive fungal infections has increased in recent years, highlighting the need for better diagnosis and more effective antifungal therapies. Amphotericin B is the drug of choice for many fungal infections, although toxicity and the need for intravenous infusion restrict its use. When possible, oral administration of antifungal agents is preferable but intravenous administration is often needed and current oral agents have their limitations: fluconazole because of a narrow spectrum of activity; itraconazole capsules because of erratic absorption. In this review, prophylactic and treatment options for systemic fungal infections are discussed. The specific needs of patients with different types of leukaemia and the benefits of new amphotericin B and itraconazole formulations are examined.

Amphotericin B↗
PubMed1999

Therapy of invasive fungal infections.

During the past decades, the incidence and severity of invasive fungal infections has been increasing. These events have lead to the development of new antifungal agents, and amphotericin B no longer is the standard therapy for a variety of invasive mycoses. Fluconazole has become the drug of choice for treatment of C. albicans infections in non-neutropenic as well as neutropenic patients. For treatment of cryptococcal meningitis, amphotericin B with flucytosine, followed by fluconazole consolidation therapy is used. For therapy of invasive aspergillosis, the lipid formulations of amphotericin B may be associated with reduced toxicity and allow for larger doses, although the efficacy of each of the formulations still has to be established in randomized trials. Finally, treatment modalities aimed at improving host defense mechanisms, including adjunctive therapy with rG-CSF for disseminated candidiasis and rG-CSF-elicited granulocyte transfusions, are under way.

Amphotericin B↗
PubMed1999

Invasive aspergillosis caused by Aspergillus ustus: case report and review.

A case of invasive pulmonary aspergillosis in an allogeneic bone marrow transplant recipient caused by Aspergillus ustus is presented. A. ustus was also recovered from the hospital environment, which may indicate that the infection was nosocomially acquired. A literature review revealed seven cases of invasive infections caused by A. ustus, and three of these were primarily cutaneous infections. In vitro susceptibility testing of 12 A. ustus isolates showed that amphotericin B and terbinafine had fungicidal activity and that itraconazole and voriconazole had fungistatic activity.

Adult↗
PubMed1999

The challenge of invasive fungal infection.

Systemic fungal infections cause almost 25% of the infection-related deaths in leukaemic patients. Particularly those with prolonged neutropenia are at risk but mycoses also feature in critically ill intensive care patients and in individuals who are treated for solid tumours and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of haemorrhages and bacterial infections in leukaemic and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

AIDS-Related Opportunistic Infections↗