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Paul E Verweij - One of the best experts on this subject based on the ideXlab platform.
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Genotyping of Aspergillus fumigatus in Formalin-Fixed Paraffin-Embedded Tissues and Serum Samples From Patients With Invasive Aspergillosis
Frontiers Media S.A., 2018Co-Authors: T. De ,groot, Paul E Verweij, Ferry Hagen, Willem Vreuls, Anuradha Chowdhary, Jacques F. MeisAbstract:Invasive Aspergillosis (IA) is a deep tissue infection with a high mortality occurring mostly in immunocompromised patients. To investigate the pathology of patients with IA it may be important to determine the genotype of the Invasive isolate of Aspergillus, however available tissues for study are often formalin fixed paraffin embedded (FFPE). Although DNA has been successfully isolated from such tissues for species identification, genotyping of Aspergillus species on such tissues has not yet been performed. In this study we aimed to determine the genotype of Aspergillus fumigatus in FFPE tissue and serum samples from five patients with Invasive Aspergillosis using nine highly polymorphic short tandem repeat (STRAf) loci. FFPE lung and bronchial biopsies from all patients were successfully typed. By comparing the latter result with non-FFPE materials from non-sterile samples such as sputum, bronchoalveolar lavage and lung abscess, we found identical genotypes within three patients, while the two other patients had a dominant genotype shared among all sample types. Genotyping of serum samples was successful in two serum samples with galactomannan ratios of 4 and 5.6, but failed in serum samples with galactomannan levels <0.5. In addition, testing a subset of these materials with the AsperGenius multiplex qPCR assay, we did not find azole resistance mutations. With this STRAf assay, A. fumigatus from FFPE tissue and serum was successfully genotyped, allowing retrospective examination of A. fumigatus in culture negative patients with IA
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successful treatment of azole resistant Invasive Aspergillosis in a bottlenose dolphin with high dose posaconazole
Medical mycology case reports, 2017Co-Authors: Paulien E Bunskoek, Willem J. G. Melchers, Seyedmojtaba Seyedmousavi, Steven J M Gans, Peter B J Van Vierzen, Cornelis E Van Elk, Johan W Mouton, Paul E VerweijAbstract:Invasive Aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant Invasive Aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose posaconazole was initiated aimed at achieving trough levels exceeding 3 mg/l. Posaconazole serum levels of 3–9.5 mg/l were achieved without significant side-effects. Follow-up bronchoscopy and computed tomography showed complete resolution of the lesions.
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azole resistance in aspergillus fumigatus a new challenge in the management of Invasive Aspergillosis
Future Microbiology, 2011Co-Authors: Eveline Snelders, Willem J. G. Melchers, Paul E VerweijAbstract:Azole resistance is emerging in Aspergillus fumigatus isolates. The exact mechanism of evolution of azole resistance has not been fully elucidated yet but increasing evidence indicates a role for azole fungicide used in agriculture. Patients confronted with an Invasive fungal infection from an azole-resistant A. fumigatus isolate will fail azole treatment. Azole resistance in A. fumigatus isolates impacts the management of Invasive Aspergillosis (IA) since the azoles are the primary agents used for prophylaxis and treatment. Because A. fumigatus will always be present in our environment and also in the close vicinity of patients at risk for IA, there is an urgent need to understand the evolution of the increasing azole resistance in A. fumigatus. Thereby, induction of azole resistance or its spread can possibly be prevented to allow future treatment of A. fumigatus IA.
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[Improved diagnostics in Invasive Aspergillosis and systematic monitoring in patients at high risk of infection]
Nederlands Tijdschrift voor Geneeskunde, 2005Co-Authors: Paul E Verweij, C.e. Van Die, J. Peter Donnelly, Nicole M. A. Blijlevens, Bart Jan Kullberg, B.e. De PauwAbstract: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
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clinical evaluation and reproducibility of the pastorex aspergillus antigen latex agglutination test for diagnosing Invasive Aspergillosis
Journal of Clinical Pathology, 1995Co-Authors: Paul E Verweij, B.e. De Pauw, Antonius J. M. M. Rijs, Alphons M Horrevorts, J A A Hoogkampkorstanje, Jacques F.g.m. MeisAbstract:AIMS--The performance of the Pastorex Aspergillus antigen latex agglutination test for the detection of galactomannan in sera of patients at risk for Invasive Aspergillosis was evaluated, and the impact of storage on the reproducibility of the antigen titre was tested. METHODS--During a one year period, 392 serum samples were obtained from 46 patients at risk for Invasive Aspergillosis and tested for the presence of galactomannan using an Aspergillus latex agglutination test (Pastorex). Twenty three positive serum samples which had been stored at -20 degrees C for 2-16 months were retrospectively retested. Furthermore, two positive serum samples were stored at -20 degrees C and -70 degrees C and prospectively tested at three month intervals for a period of 15 months. RESULTS--The Pastorex Aspergillus test was positive in eight patients with microbiological, radiological, or histological evidence for Invasive Aspergillosis, but was negative in the initial serum sample from five of these patients. In two patients with histological evidence for Invasive Aspergillosis no positive reaction was found in six samples. Six of 13 (45%) serum samples which had been stored at -20 degrees C for longer than six months had lost reactivity, while one of 10 (10%) samples had lost reactivity when stored up to six months. Two serum samples which had been stored at -20 degrees C and -70 degrees C and prospectively retested at three month intervals for 15 months, maintained stable antigen titres. CONCLUSIONS--The Pastorex Aspergillus test is too insensitive to diagnose Invasive Aspergillosis in an early stage, but may contribute to the diagnosis when cultures remain negative and serial samples are obtained. To maintain a good reproducibility, serum samples should be stored at -70 degrees C when the period of storage exceeds six months.
Jean-paul Latgé - One of the best experts on this subject based on the ideXlab platform.
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aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase for development of Invasive Aspergillosis
Infection and Immunity, 2007Co-Authors: Felicitas Schobel, Jean-paul Latgé, Oumaima Ibrahimgranet, Patrick Ave, Axel A Brakhage, Matthias BrockAbstract:Aspergillus fumigatus is the most prevalent airborne filamentous fungus causing Invasive Aspergillosis in immunocompromised individuals. Only a limited number of determinants directly associated with virulence are known, and the metabolic requirements of the fungus to grow inside a host have not yet been investigated. Previous studies on pathogenic microorganisms, i.e., the bacterium Mycobacterium tuberculosis and the yeast Candida albicans, have revealed an essential role for isocitrate lyase in pathogenicity. In this study, we generated an isocitrate lyase deletion strain to test whether this strain shows attenuation in virulence. Results have revealed that isocitrate lyase from A. fumigatus is not required for the development of Invasive Aspergillosis. In a murine model of Invasive Aspergillosis, the wild-type strain, an isocitrate lyase deletion strain, and a complemented mutant strain were similarly effective in killing mice. Moreover, thin sections demonstrated Invasive growth of all strains. Additionally, thin sections of lung tissue from patients with Invasive Aspergillosis stained with anti-isocitrate lyase antibodies remained negative. From these results, we cannot exclude the use of lipids or fatty acids as a carbon source for A. fumigatus during Invasive growth. Nevertheless, test results do imply that the glyoxylate cycle from A. fumigatus is not required for the anaplerotic synthesis of oxaloacetate under infectious conditions. Therefore, an antifungal drug inhibiting fungal isocitrate lyases, postulated to act against Candida infections, is assumed to be ineffective against A. fumigatus.
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survival and prognostic factors of Invasive Aspergillosis after allogeneic bone marrow transplantation
Clinical Infectious Diseases, 1999Co-Authors: Patricia Ribaud, Jean-paul Latgé, Claude Chastang, Laurence Baffroylafitte, Nathalie Natquet, A Devergie, Helene Esperou, Fadhela Selimi, Vanderson Rocha, Francis DerouinAbstract:To determine prognostic factors for survival in bone marrow transplant recipients with Invasive Aspergillosis (IA), we retrospectively reviewed 27 IA cases observed in our bone marrow transplantation unit between January 1994 and October 1994. On 30 September 1997, six patients were alive and disease-free. The median survival after IA diagnosis was 36 days. Of eight variables found to be related to survival according to the univariate analysis, graft-versus-host disease (GVHD) status at IA diagnosis (P = .0008) and the cumulative prednisolone dose taken during the week preceding IA diagnosis (CPDlw) (P 7 mglkg and no GVHD (9 of 10 patients died; 60-day survival rate, 20%), and CPDlw of >7 mglkg and active acute grade 2 or more or extensive chronic GVHD (9 of 9 patients died; 30-day survival rate, 0) (P <.0001).
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prospective sandwich enzyme linked immunosorbent assay for serum galactomannan early predictive value and clinical use in Invasive Aspergillosis
Pediatric Infectious Disease Journal, 1996Co-Authors: Pierre Rohrlich, Jean-paul Latgé, J Sarfati, Patricia Mariani, Michel Duval, Agnes Carol, Catherine Saintmartin, E Bingen, Etienne VilmerAbstract:BackgroundThe delay between the onset of Invasive Aspergillosis and the start of antifungal therapy is crucial for the patient's recovery. Early diagnosis is difficult in cancer patients through lack of precocious specific signs. We have investigated the clinical usefulness of circulating Aspergillu
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A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with Invasive Aspergillosis
Journal of Clinical Microbiology, 1995Co-Authors: D Stynen, Annelies Goris, Jacqueline Sarfati, Jean-paul LatgéAbstract:A double-direct sandwich enzyme-linked immunosorbent assay that uses a rat anti-galactomannan monoclonal antibody as the acceptor and detector antibody was designed. This immunoassay, which detects less than 1 ng of galactomannan per ml, was assessed in a retrospective study with samples from patients with Invasive Aspergillosis. Serum is more appropriate than urine for use in the search for circulating galactomannan. Antigenemia does not have a transient character. Galactomannan can be detected at least 39 days before the death of the patients.
Thomas F. Patterson - One of the best experts on this subject based on the ideXlab platform.
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treatment of Invasive Aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy an externally controlled trial
Clinical Infectious Diseases, 2007Co-Authors: Thomas J Walsh, Thomas F. Patterson, Reginald Greene, Issam I Raad, Pranatharthi H Chandrasekar, Gerald R Donowitz, Richard J Graybill, Ray Y Hachem, Susan Hadley, Raoul HerbrechtAbstract:Background Invasive Aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. Methods We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with Invasive Aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. Results Cases of Aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. Conclusions Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with Invasive Aspergillosis who are refractory to or intolerant of previous antifungal therapy.
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strategy of following voriconazole versus amphotericin b therapy with other licensed antifungal therapy for primary treatment of Invasive Aspergillosis impact of other therapies on outcome
Clinical Infectious Diseases, 2005Co-Authors: Thomas F. Patterson, Raoul Herbrecht, David W Denning, Helen W. Boucher, Olivier Lortholary, Patricia Ribaud, Robert H. Rubin, John R. Wingard, Ben E. Depauw, Haran T. SchlammAbstract:Background. In a previous randomized trial of voriconazole versus amphotericin B deoxycholate for primary therapy of Invasive Aspergillosis, voriconazole demonstrated superior efficacy and better survival. In that trial, treatment with voriconazole or amphotericin B deoxycholate could be followed with other licensed antifungal therapies (OLAT). Here, we report the impact of OLAT on the outcome of patients with Invasive Aspergillosis. Methods. Data on dose, duration, and the reason for switching to the first OLAT were analyzed, and outcome at week 12 was assessed. Results. Fewer patients in the voriconazole group (52 [36%] of 144) switched to OLAT, compared with patients in the amphotericin B deoxycholate group (107 [80%] of 133). Lipid formulations of amphotericin B were the most common OLAT (38% of patients). Switches were made because of intolerance or insufficient response in 70% for patients in the amphotericin B deoxycholate group, compared with 24% of patients in the voriconazole group. Favorable responses to OLAT in the amphotericin B deoxycholate group occurred in only 19% of patients with initial insufficient response and 38% of patients with intolerance. Salvage therapy with a lipid formulation of amphotericin B after initial treatment with amphotericin B deoxycholate was successful for only 30% of patients (14 of 47). Treatment success among patients randomized to receive amphotericin B, including those whose treatment was switched to OLAT, was 32%, compared with 55% among patients who received voriconazole alone (P<.001). Conclusions. This study highlights the limited efficacy of salvage antifungal therapy, including therapy with lipid formulations of amphotericin B, and demonstrates the importance of effective initial therapy in Invasive Aspergillosis.
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voriconazole versus amphotericin b for primary therapy of Invasive Aspergillosis
The New England Journal of Medicine, 2002Co-Authors: Raoul Herbrecht, David W Denning, Thomas F. Patterson, John E Bennett, Reginald Greene, J W Oestmann, Winfried V KernAbstract:BACKGROUND: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of Invasive Aspergillosis. METHODS: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. RESULTS: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable Aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). CONCLUSIONS: In patients with Invasive Aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.
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voriconazole versus amphotericin b for primary therapy of Invasive Aspergillosis
The New England Journal of Medicine, 2002Co-Authors: Raoul Herbrecht, David W Denning, Thomas F. Patterson, John E Bennett, Reginald Greene, J W Oestmann, Winfried V KernAbstract:Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of Invasive Aspergillosis. Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable Aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematop...
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efficacy of voriconazole in a guinea pig model of disseminated Invasive Aspergillosis
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: William R. Kirkpatrick, Robert K Mcatee, Annette W Fothergill, Michael G Rinaldi, Thomas F. PattersonAbstract:Voriconazole (VRC) was evaluated in an immunosuppressed-guinea pig model of Invasive Aspergillosis. VRC was more effective than amphotericin B or similar doses of itraconazole in the clearance of Aspergillus from tissues. VRC treatment regimens improved survival and significantly reduced tissue colony counts compared with those of controls.
David W Denning - One of the best experts on this subject based on the ideXlab platform.
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strategy of following voriconazole versus amphotericin b therapy with other licensed antifungal therapy for primary treatment of Invasive Aspergillosis impact of other therapies on outcome
Clinical Infectious Diseases, 2005Co-Authors: Thomas F. Patterson, Raoul Herbrecht, David W Denning, Helen W. Boucher, Olivier Lortholary, Patricia Ribaud, Robert H. Rubin, John R. Wingard, Ben E. Depauw, Haran T. SchlammAbstract:Background. In a previous randomized trial of voriconazole versus amphotericin B deoxycholate for primary therapy of Invasive Aspergillosis, voriconazole demonstrated superior efficacy and better survival. In that trial, treatment with voriconazole or amphotericin B deoxycholate could be followed with other licensed antifungal therapies (OLAT). Here, we report the impact of OLAT on the outcome of patients with Invasive Aspergillosis. Methods. Data on dose, duration, and the reason for switching to the first OLAT were analyzed, and outcome at week 12 was assessed. Results. Fewer patients in the voriconazole group (52 [36%] of 144) switched to OLAT, compared with patients in the amphotericin B deoxycholate group (107 [80%] of 133). Lipid formulations of amphotericin B were the most common OLAT (38% of patients). Switches were made because of intolerance or insufficient response in 70% for patients in the amphotericin B deoxycholate group, compared with 24% of patients in the voriconazole group. Favorable responses to OLAT in the amphotericin B deoxycholate group occurred in only 19% of patients with initial insufficient response and 38% of patients with intolerance. Salvage therapy with a lipid formulation of amphotericin B after initial treatment with amphotericin B deoxycholate was successful for only 30% of patients (14 of 47). Treatment success among patients randomized to receive amphotericin B, including those whose treatment was switched to OLAT, was 32%, compared with 55% among patients who received voriconazole alone (P<.001). Conclusions. This study highlights the limited efficacy of salvage antifungal therapy, including therapy with lipid formulations of amphotericin B, and demonstrates the importance of effective initial therapy in Invasive Aspergillosis.
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laboratory diagnosis of Invasive Aspergillosis
Lancet Infectious Diseases, 2005Co-Authors: William W Hope, Thomas J Walsh, David W DenningAbstract:Invasive Aspergillosis occurs in a wide range of clinical scenarios, is protean in its manifestations, and is still associated with an unacceptably high mortality rate. Early diagnosis is critical to a favourable outcome, but is difficult to achieve with current methods. Deep tissue diagnostic specimens are often difficult to obtain from critically ill patients. Newer antifungal agents exhibit differential mould activity, thus increasing the importance of establishing a specific diagnosis of Invasive Aspergillosis. For these reasons, a range of alternate diagnostic strategies have been investigated. Most investigative efforts have focused on molecular and serological diagnostic techniques. The detection of metabolites produced by Aspergillus spp and a range of aspergillus-specific antibodies represent additional, but relatively underused, diagnostic avenues. The detection of galactomannan has been incorporated into diagnostic criteria for Invasive Aspergillosis, reflecting an increased understanding of the performance, utility, and limitations of this technique. Measurement of (1,3)-beta-D glucan in blood may be useful as a preliminary screening tool for Invasive Aspergillosis, despite the fact that this antigen can be detected in a number of other fungi. There have been extensive efforts directed toward the detection of Aspergillus spp DNA, but a lack of technical standardisation and relatively poor understanding of DNA release and kinetics continues to hamper the broad applicability of this technique. This review considers the application, utility, and limitations of the currently available and investigational diagnostic modalities for Invasive Aspergillosis.
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voriconazole versus amphotericin b for primary therapy of Invasive Aspergillosis
The New England Journal of Medicine, 2002Co-Authors: Raoul Herbrecht, David W Denning, Thomas F. Patterson, John E Bennett, Reginald Greene, J W Oestmann, Winfried V KernAbstract:BACKGROUND: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of Invasive Aspergillosis. METHODS: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. RESULTS: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable Aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). CONCLUSIONS: In patients with Invasive Aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.
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voriconazole versus amphotericin b for primary therapy of Invasive Aspergillosis
The New England Journal of Medicine, 2002Co-Authors: Raoul Herbrecht, David W Denning, Thomas F. Patterson, John E Bennett, Reginald Greene, J W Oestmann, Winfried V KernAbstract:Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of Invasive Aspergillosis. Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable Aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematop...
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therapeutic outcome in Invasive Aspergillosis
Clinical Infectious Diseases, 1996Co-Authors: David W DenningAbstract:A review of series of > or = 4 cases of Invasive Aspergillosis (total, 1,223 cases) was undertaken to establish the crude mortality and rate of response to therapy with amphotericin B in the major at-risk host groups. In association with pulmonary, sinus, and cerebral Aspergillosis in immunocompromised patients, the crude mortality rates were 86%, 66%, and 99%, respectively. No untreated patient survived. Among 84 patients treated for 1-13 days, only one survived. Among those with Invasive pulmonary Aspergillosis treated for > or = 14 days, the response rates to amphotericin B deoxycholate were 83% (in cases of heart and renal transplantation), 54% (leukemia), 33% (bone marrow transplantation) and 20% (liver transplantation). Patients with AIDS mostly received both amphotericin B and itraconazole, and 37% of those treated for > or = 14 days responded to therapy. Substantial variation in outcome from series to series was related to underlying disease status, site of disease, and management. Invasive Aspergillosis remains a devastating opportunistic infection despite current treatment.
D Stynen - One of the best experts on this subject based on the ideXlab platform.
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A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with Invasive Aspergillosis
Journal of Clinical Microbiology, 1995Co-Authors: D Stynen, Annelies Goris, Jacqueline Sarfati, Jean-paul LatgéAbstract:A double-direct sandwich enzyme-linked immunosorbent assay that uses a rat anti-galactomannan monoclonal antibody as the acceptor and detector antibody was designed. This immunoassay, which detects less than 1 ng of galactomannan per ml, was assessed in a retrospective study with samples from patients with Invasive Aspergillosis. Serum is more appropriate than urine for use in the search for circulating galactomannan. Antigenemia does not have a transient character. Galactomannan can be detected at least 39 days before the death of the patients.
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Sandwich enzyme-linked immunosorbent assay compared with pastorex latex agglutination test for diagnosing Invasive Aspergillosis in immunocompromised patients
Journal of Clinical Microbiology, 1995Co-Authors: Paul E Verweij, B.e. De Pauw, D Stynen, Antonius J. M. M. Rijs, Jacomina A. A. Hoogkamp-korstanje, Jacques F.g.m. MeisAbstract:The performance of a direct sandwich enzyme-linked immunosorbent assay (ELISA) for detecting Aspergillus galactomannan was compared with that of the Pastorex Aspergillus antigen latex agglutination (LA) test by using 532 serum samples from 61 patients at risk for Invasive Aspergillosis. The ELISA gave positive results earlier in the course of infection than did the LA test. A sensitivity of 70% and a specificity of 86% were obtained for the LA test and corresponding values of 90 and 84% were obtained for the ELISA when a series of serum samples was employed.
