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Winfried V Kern - One of the best experts on this subject based on the ideXlab platform.
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voriconazole versus <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> B.
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voriconazole versus <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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...
David W. Denning - One of the best experts on this subject based on the ideXlab platform.
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voriconazole versus <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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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voriconazole versus <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> B.
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dose range evaluation of liposomal nystatin and comparisons with <B>AmphotericinB> B and <B>AmphotericinB> B lipid complex in temporarily neutropenic mice infected with an isolate of aspergillus fumigatus with reduced susceptiBility to <B>AmphotericinB> B
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: David W. Denning, Peter WarnAbstract:Using an isolate of Aspergillus fumigatus that is less susceptiBle in vivo to <B>AmphotericinB> B than most other isolates, we compared different doses of liposomal nystatin (L-nystatin), liposomal <B>AmphotericinB> B (L-<B>AmphotericinB>), and <B>AmphotericinB> B lipid complex (ABLC) with <B>AmphotericinB> B deoxycholate. Four experiments with intravenously infected neutropenic mice were conducted. A dose of L-nystatin at 10 mg/kg of Body weight was toxic (the mice had fits or respiratory arrest). The optimal dosage of L-nystatin was 5 mg/kg daily on days 1, 2, 4, and 7 (90% survival). This was superior to L-<B>AmphotericinB> (5 mg/kg [P = 0.24] and 1 mg/kg [P < 0.0001]), ABLC (5 mg/kg [P = 0.014] and 1 mg/kg [P < 0.0001]), and <B>AmphotericinB> B deoxycholate (5 mg/kg [P = 0.008]). In terms of liver and kidney cultures, L-nystatin (5 mg/kg) was superior to all other regimens (P = 0.0032 and <0.0001, respectively). Higher doses of L-<B>AmphotericinB> (25 and 50 mg/kg) in one earlier experiment were more effective (100% survival) than 1 mg of L-<B>AmphotericinB> per kg and <B>AmphotericinB> deoxycholate (5 mg/kg) in terms of mortality and Both liver and kidney culture results and to L-<B>AmphotericinB> (5 mg/kg) in terms of liver and kidney culture results only. ABLC (25 mg/kg) given daily for 7 days was superior to ABLC (50 mg/kg [P = 0.03]) But not to ABLC at 5 mg/kg or <B>AmphotericinB> B deoxycholate in terms of mortality, although it was in terms of liver and kidney culture results. No dose-response for <B>AmphotericinB> B (5 and 1 mg/kg) was demonstraBle. In conclusion, in this stringent model, high doses of L-<B>AmphotericinB> and ABLC could overcome reduced susceptiBility to <B>AmphotericinB> B deoxycholate, But all were inferior to 5- to 10-fold lower doses of L-nystatin.
Thomas J. Walsh - One of the best experts on this subject based on the ideXlab platform.
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efficacy of <B>AmphotericinB> B in corneal preservation media after extended frozen storage
Cornea, 2020Co-Authors: Doowon Huh, Thomas J. Walsh, Khoa D Tran, Megan M W Straiko, Matthew W Mccarthy, Angela S Loo, Christopher S SalesAbstract:PURPOSE To investigate the antimycotic activity of <B>AmphotericinB> B deoxycholate that has Been previously frozen for 28 days Before supplementation of Optisol-GS. METHODS Triplicate Optisol-GS samples were inoculated with 10 colony-forming units (CFU) of Candida alBicans. Each set of triplicate cultures was supplemented with 2.5 μg/mL of <B>AmphotericinB> B that was either freshly resuspended and never frozen, frozen overnight at -20°C and thawed, or frozen at -20°C for 4 weeks and thawed. The cultures were stored at 4°C, with aliquots taken at 0, 6, 24, and 72 hours for quantification. The efficacy of each preparation of <B>AmphotericinB> B in reducing C. alBicans growth was assessed at these time points. RESULTS Six hours after antifungal supplementation, there was a 1.33 log10 CFU reduction with freshly resuspended <B>AmphotericinB> B, compared with a 1.31 log10 reduction with <B>AmphotericinB> B that was frozen overnight (P = 0.20) and a 1.18 log10 reduction with <B>AmphotericinB> B that was frozen for 4 weeks (P = 0.05). After 72 hours, there was a 2.72 log10 CFU reduction with freshly resuspended <B>AmphotericinB> B, a 2.64 log10 CFU reduction with <B>AmphotericinB> B that was frozen overnight (P = 0.45), and a 2.18 log10 CFU reduction with <B>AmphotericinB> B that was frozen for 4 weeks (P = 0.05). CONCLUSIONS Previously frozen <B>AmphotericinB> B remains highly effective against C. alBicans. Optisol-GS supplemented with 2.5 μg/mL <B>AmphotericinB> B that was frozen for 4 weeks at -20°C resulted in >90% CFU reduction By 6 hours and >99% reduction By 72 hours.
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Pharmacodynamics of <B>AmphotericinB> B Deoxycholate, <B>AmphotericinB> B Lipid Complex, and Liposomal <B>AmphotericinB> B against Aspergillus fumigatus
Antimicrobial agents and chemotherapy, 2015Co-Authors: Zaid Al-nakeeb, Joanne Goodwin, Thomas J. Walsh, Vidmantas Petraitis, Ruta Petraitiene, William W. HopeAbstract:<B>AmphotericinB> B is a first-line agent for the treatment of invasive aspergillosis. However, relatively little is known aBout the pharmacodynamics of <B>AmphotericinB> B for invasive pulmonary aspergillosis. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of <B>AmphotericinB> B deoxycholate (DAMB), <B>AmphotericinB> B lipid complex (ABLC), and liposomal <B>AmphotericinB> B (LAMB) By using a neutropenic-raBBit model of invasive pulmonary aspergillosis. The study endpoints were lung weight, infarct score, and levels of circulating galactomannan and (1 → 3)-β-D-glucan. Mathematical models were used to descriBe PK-PD relationships. The experimental findings were Bridged to humans By Monte Carlo simulation. Each <B>AmphotericinB> B formulation induced a dose-dependent decline in study endpoints. Near-maximal antifungal activity was evident with DAMB at 1 mg/kg/day and ABLC and LAMB at 5 mg/kg/day. The Bridging study suggested that the "average" patient receiving LAMB at 3 mg/kg/day was predicted to have complete suppression of galactomannan and (1 → 3)-β-D-glucan levels, But 20 to 30% of the patients still had a galactomannan index of >1 and (1 → 3)-β-D-glucan levels of >60 pg/ml. All formulations of <B>AmphotericinB> B induce a dose-dependent reduction in markers of lung injury and circulating fungus-related Biomarkers. A clinical dosage of liposomal <B>AmphotericinB> B of 3 mg/kg/day is predicted to cause complete suppression of galactomannan and (1 → 3)-β-D-glucan levels in the majority of patients.
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Pharmacokinetics and pharmacodynamics of <B>AmphotericinB> B deoxycholate, liposomal <B>AmphotericinB> B, and <B>AmphotericinB> B lipid complex in an in vitro model of invasive pulmonary aspergillosis
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Jodi M Lestner, Jayesh Majithiya, Gerard M. Jensen, Lea Gregson, Susan J Howard, Joanne Goodwin, Thomas J. Walsh, William W. HopeAbstract:The pharmacodynamic and pharmacokinetic (PK-PD) properties of <B>AmphotericinB> B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of <B>AmphotericinB> B deoxycholate (DAmB), liposomal <B>AmphotericinB> B (LAmB) and <B>AmphotericinB> B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined By measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal Biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-laBeled liposomes. The MICs for the pure compound and the three formulations were comparaBle (0.125 to 0.25 mg/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distriButed into the cellular Bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC50) in the endovascular compartment were 0.12, 1.03, and 4.41 mg/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC50 in the alveolar compartment were 0.17, 7.76, and 39.34 mg/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an in vitro lung model of IPA.
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deoxycholate <B>AmphotericinB> B and <B>AmphotericinB> B lipid complex exert additive antifungal activity in comBination with pulmonary alveolar macrophages against fusarium solani
Mycoses, 2006Co-Authors: Emmanuel Roilides, Ruta Petraitiene, Caron A Lyman, Derek T Armstrong, Theodouli Stergiopoulou, Thomas J. WalshAbstract:Summary Fusarium spp. have emerged as important causes of invasive fungal infections in immunocompromised patients. RaBBit pulmonary alveolar macrophages (PAMs) exhiBited fungicidal activity against conidia of Fusarium solani and achieved a time-dependent increase in killing. Neither deoxycholate <B>AmphotericinB> B (DAMB) nor <B>AmphotericinB> B lipid complex (ABLC) exerted a suppressive effect on PAMs By decreasing their conidiocidal activity against F. solani. On the contrary, at a concentration of 0.125 μg ml−1, ABLC and, to a lesser degree, DAMB additively augmented the fungicidal activity of pulmonary alveolar macrophages against conidia of Fusarium solani.
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liposomal <B>AmphotericinB> B for empirical therapy in patients with persistent fever and neutropenia
The New England Journal of Medicine, 1999Co-Authors: Thomas J. Walsh, Robert W Finberg, Carola A S Arndt, John W Hiemenz, Cindy L Schwartz, David C Bodensteiner, Peter G Pappas, Nita Seibel, Richard N Greenberg, Stephen DummerAbstract:Background In patients with persistent fever and neutropenia, <B>AmphotericinB> B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, Breakthrough fungal infections can develop despite treatment, and <B>AmphotericinB> B has suBstantial toxicity. Methods We conducted a randomized, douBle-Blind, multicenter trial comparing liposomal <B>AmphotericinB> B with conventional <B>AmphotericinB> B as empirical antifungal therapy. Results The mean duration of therapy was 10.8 days for liposomal <B>AmphotericinB> B (343 patients) and 10.3 days for conventional <B>AmphotericinB> B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal <B>AmphotericinB> B and 49 percent for conventional <B>AmphotericinB> B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal <B>AmphotericinB> B and conventional <B>AmphotericinB> B with respect to survival (93 percent and 90 percent, respective...
Raoul Herbrecht - One of the best experts on this subject based on the ideXlab platform.
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voriconazole versus <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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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voriconazole versus <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> 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 <B>AmphotericinB> B.
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treatment of 21 cases of invasive mucormycosis with <B>AmphotericinB> B colloidal dispersion
European Journal of Clinical Microbiology & Infectious Diseases, 2001Co-Authors: Raoul Herbrecht, Shimon Kusne, John R. Graybill, Raleigh A. Bowden, Gary A. Noskin, Elias Anaissie, Beryl A Oppenheim, Valerie Letscherbru, Emmanuel Andres, L PietrelliAbstract:The aim of this study was to review the characteristics and outcome of 21 patients with invasive mucormycosis treated with <B>AmphotericinB> B colloidal dispersion (ABCD) in five phase I and phase II studies. Mucormycosis is an increasing concern in immunocompromised patients, in whom mortality exceeds 60%. The standard treatment has Been <B>AmphotericinB> B comBined with surgical deBridement. Twenty-one patients with invasive mucormycosis treated with ABCD, a lipid complex of <B>AmphotericinB> B and cholesteryl sulfate, were identified. Patients were given ABCD on the Basis of pre-existing renal insufficiency, development of nephrotoxicity during <B>AmphotericinB> B therapy, or fungal infection that failed to respond to <B>AmphotericinB> B. Response could Be evaluated in 20 patients, all of whom had Bone marrow or organ transplantation, haematologic malignancies, or diaBetes. Infection was disseminated in six patients and localised to the sinuses, lower respiratory tract, or skin in the other patients. ABCD was given at a mean dose of 4.8 mg/kg per infusion for a mean duration of 37 days. Twelve of 20 patients responded to ABCD therapy. Response rates were similar when patients were treated with ABCD alone (4/7) and ABCD comBined with surgery (8/13), with more complete response oBtained in the latter group. No difference in response rate was oBserved in leukaemic patients (3/5) or transplant recipients (6/10) compared to diaBetics (3/5). No renal or hepatic toxicity was oBserved. These results compare favouraBly with the results of standard treatment and suggest that ABCD comBined with surgery may Be a useful therapy in patients with mucormycosis.
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liposomal <B>AmphotericinB> B compared with <B>AmphotericinB> B deoxycholate in the treatment of documented and suspected neutropenia associated invasive fungal infections
British Journal of Haematology, 1998Co-Authors: Acap Leenders, Simon Daenen, Rlh Jansen, Wcj Hop, Bob Löwenberg, Pierre W. Wijermans, Jan J. Cornelissen, Raoul Herbrecht, H Van Der Lelie, Henk C. HoogstedenAbstract:It has Been suggested that a Better outcome of neutropenia-associated invasive fungal infections can Be achieved when high doses of lipid formulations of <B>AmphotericinB> B are used. We now report a randomized multicentre study comparing liposomal <B>AmphotericinB> B (AmBisome, 5 mg/kg/d) to <B>AmphotericinB> B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possiBle patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favouraBle trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their Baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.
Karl V Clemons - One of the best experts on this subject based on the ideXlab platform.
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<B>AmphotericinB> B concentrations in healthy mallard ducks anas platyrhynchos following a single intratracheal dose of liposomal <B>AmphotericinB> B using an atomizer
Medical Mycology, 2018Co-Authors: Ashley Phillips, Christine V Fiorello, Rachel M Baden, Nathaniel C Burmas, Carlos Abraham Ruvalcaba, Roger Monroy, Frederick C Mohr, Ronette Gehring, Jean Pierre Delplanque, Karl V ClemonsAbstract:: Aspergillosis is a fungal infection that primarily affects the respiratory tract. <B>AmphotericinB> B has Broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other Birds in wildlife rehaBilitation. Pharmacokinetic parameters of neBulized <B>AmphotericinB> B in an avian model have Been reported, But those of direct intratracheal delivery have yet to Be estaBlished. The oBjective of this study was to evaluate if a single 3 mg/kg dose of liposomal <B>AmphotericinB> B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhiBitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos). Following intratracheal delivery, <B>AmphotericinB> B was present in lung parenchyma at concentrations aBove the targeted MIC of 1 μg/g for up to 9 days post-administration; however, distriBution of the drug was uneven, with the majority of the drug concentrated in one lung loBe. Concentrations in the contralateral lung loBe and the kidneys were aBove the targeted MIC 1 day after administration But declined exponentially with a half-life of approximately 2 days. Plasma concentrations were never aBove the targeted MIC. Histological examination of the trachea, Bronchi, lungs, heart, liver, and kidneys did not reveal any toxic changes. Using a commercial atomizer, intratracheal delivery of <B>AmphotericinB> B at 3 mg/kg resulted in lung parenchyma concentrations aBove 1 μg/ml with no discernaBle systemic effects. Further studies to estaBlish a system of drug delivery to Both sides of the pulmonary parenchyma need to Be performed, and the efficacy of this treatment for disease prevention remains to Be determined.
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comparative toxicities and pharmacokinetics of intrathecal lipid <B>AmphotericinB> B colloidal dispersion and conventional deoxycholate formulations of <B>AmphotericinB> B in raBBits
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: Karl V Clemons, Raymond A Sobel, Paul L Williams, David A StevensAbstract:The lipid formulation of <B>AmphotericinB> B, Amphotec (ABCD), has not Been used intrathecally. After a single intrathecal dose or after four doses, conventionally formulated deoxycholate <B>AmphotericinB> B (AMB) (Fungizone) resulted in higher levels of <B>AmphotericinB> B in the cereBrospinal fluid of raBBits than did ABCD. Clinically and histologically, ABCD was aBout threefold less toxic than AMB after a single dose and 3- to 30-fold less toxic after multiple dosing. These data are encouraging for the potential use of ABCD as an intrathecal treatment.
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comparative efficacy of <B>AmphotericinB> B colloidal dispersion and <B>AmphotericinB> B deoxycholate suspension in treatment of murine coccidioidomycosis
Antimicrobial Agents and Chemotherapy, 1991Co-Authors: Karl V Clemons, D A StevensAbstract:The efficacy of a novel sterol-complexed preparation of <B>AmphotericinB> B, <B>AmphotericinB> B colloidal dispersion, was compared with that of deoxycholate-complexed <B>AmphotericinB> B in an acute murine model of systemic coccidioidomycosis. Mice (CD-1, female) were infected intravenously with 180 or 200 arthroconidia of Coccidioides immitis, and intravenous therapy was Begun 3 days later. Six doses in various regimens of either preparation were given over 14 days, and deaths were tallied for an additional 35 days. All regimens that were not acutely lethal prolonged the survival of mice over that of controls (P less than 0.001). Quantitative determination of residual Burdens of C. immitis in the spleen, liver, and lungs of survivors revealed that the colloidal dispersion was not as effective as the deoxycholate suspension on a milligram-per-kilogram Basis. Deoxycholate suspension at 1.3 mg/kg cleared the organs in all mice, whereas colloidal dispersion at 5.0 mg/kg was the lowest dose that cleared organisms from all animals. Lower doses cleared organisms from fewer animals or cleared only selected organs. Deoxycholate suspension was more efficacious than colloidal dispersion in clearing C. immitis from the liver or lungs (P less than 0.05 to 0.01, dose and organ dependent) at identical doses. No overt toxicity was oBserved in mice treated with colloidal dispersion at 10 mg/kg. In contrast, deoxycholate suspension at 2.0 mg/kg was acutely toxic; 50% of the treated mice died after treatment. The two complexes were not equivalent on a milligram-per-kilogram Basis; the deoxycholate suspension was three to four times more efficacious and also greater than 5- to greater than or equal to 8-fold more toxic. Thus, the therapeutic index of the colloidal dispersion complex is greater than that of the deoxycholate complex. The amount of <B>AmphotericinB> B per dose could also Be increased when given as a colloidal dispersion to an optimally level. <B>AmphotericinB> B colloidal dispersion shows promise for the therapy of disseminated coccidioidomycosis and should Be tested in other animal models and in humans.