8 results on '"Schlamm, Haran T"'
Search Results
2. Fosmanogepix Therapy of Disseminated Fusarium Infection.
- Author
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Winston DJ, Young PA, Schlamm HT, and Schiller GJ
- Subjects
- Humans, Female, Antifungal Agents therapeutic use, Central Nervous System, Fusariosis drug therapy, Fusariosis microbiology, Leukemia, Myeloid, Acute drug therapy
- Abstract
Invasive Fusarium infections cause high mortality. Fosmanogepix, a first-in-class antifungal agent, has potent activity against Fusarium. A patient with acute leukemia with invasive fusariosis, probably involving the central nervous system and caused by Fusarium lactis resistant to currently available antifungal agents, was cured of her infection with fosmanogepix. Fosmanogepix was well tolerated., Competing Interests: Potential conflicts of interest. H. T. S. is a consultant to Pfizer, Inc. The fosmanogepix was provided by Amplyx Pharmaceuticals, California, which has been acquired by Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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3. Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.
- Author
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Herbrecht R, Patterson TF, Slavin MA, Marchetti O, Maertens J, Johnson EM, Schlamm HT, Donnelly JP, and Pappas PG
- Subjects
- Adolescent, Adult, Aged, Child, Female, Humans, Male, Middle Aged, Prospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Invasive Pulmonary Aspergillosis drug therapy, Voriconazole therapeutic use
- Abstract
Background: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions., Methods: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged., Results: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA., Conclusions: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
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4. Ocular manifestations of candidemia.
- Author
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Oude Lashof AM, Rothova A, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, Schlamm HT, Oborska IT, Rex JH, and Kullberg BJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Amphotericin B administration & dosage, Antifungal Agents administration & dosage, Candidemia drug therapy, Endophthalmitis epidemiology, Endophthalmitis microbiology, Eye Infections, Fungal drug therapy, Female, Fluconazole administration & dosage, Humans, Incidence, Male, Middle Aged, Prospective Studies, Pyrimidines administration & dosage, Risk Factors, Triazoles administration & dosage, Voriconazole, Young Adult, Candida isolation & purification, Candidemia complications, Eye Infections, Fungal epidemiology, Eye Infections, Fungal microbiology
- Abstract
Background: Ocular candidiasis is a major complication of candidemia. The incidence, risk factors, and outcome of eye involvement during candidemia are largely unknown. We prospectively studied the ocular manifestations of candidemia in a large, worldwide, randomized multicenter trial that compared voriconazole with amphotericin B followed by fluconazole for the treatment of candidemia., Methods: Nonneutropenic patients with blood cultures positive for Candida species were assigned treatment with voriconazole or with amphotericin B followed by fluconazole in a randomized 2:1 ratio. Dilated fundoscopy was performed in each patient at baseline, on day 7, at 2 and 6 weeks after the end of treatment (EOT), and, if clinically indicated, at 12 weeks after EOT., Results: Of 370 patients, 49 had findings consistent with the diagnosis of ocular candidiasis at baseline, and an additional 11 patients developed abnormalities during treatment, totaling 60 patients with eye involvement (16%). Of these patients, probable Candida eye infection was diagnosed in 40 patients (6 with endophthalmitis, 34 with chorioretinitis), and possible Candida eye infection in 20 (all with chorioretinitis). The duration of candidemia was significantly longer in patients with ocular candidiasis (median, 4 days; range, 1-18 days) compared with patients without ocular involvement (median, 3 days; range 1-26 days; log rank, P = .026). Therapy with either voriconazole (44 cases) or amphotericin B followed by fluconazole (16 cases) was successful in 65% of patients; outcome was not evaluable in 32% and was unfavorable in 3%., Conclusions: Ocular involvement occurred in 16% of patients with candidemia; however, endophthalmitis was uncommon (1.6%). Treatment with either voriconazole or amphotericin B followed by fluconazole was successful for ocular candidiasis in most cases with follow-up.
- Published
- 2011
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5. An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis.
- Author
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Queiroz-Telles F, Goldani LZ, Schlamm HT, Goodrich JM, Espinel-Ingroff A, and Shikanai-Yasuda MA
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- Administration, Oral, Adult, Aged, Aged, 80 and over, Antifungal Agents administration & dosage, Antifungal Agents therapeutic use, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Pilot Projects, Voriconazole, Itraconazole administration & dosage, Itraconazole therapeutic use, Paracoccidioidomycosis drug therapy, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Triazoles administration & dosage, Triazoles therapeutic use
- Abstract
Background: In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment., Methods: A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2 : 1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving >or=1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed >or=6 months of therapy (treatment-evaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment., Results: Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up., Conclusions: This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective as itraconazole for the long-term treatment of paracoccidioidomycosis.
- Published
- 2007
- Full Text
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6. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign.
- Author
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Greene RE, Schlamm HT, Oestmann JW, Stark P, Durand C, Lortholary O, Wingard JR, Herbrecht R, Ribaud P, Patterson TF, Troke PF, Denning DW, Bennett JE, de Pauw BE, and Rubin RH
- Subjects
- Adolescent, Adult, Aged, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Aspergillosis mortality, Child, Female, Humans, Immunocompromised Host, Lung pathology, Lung Diseases, Fungal drug therapy, Lung Diseases, Fungal mortality, Lung Diseases, Fungal pathology, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Survival Analysis, Aspergillosis diagnostic imaging, Lung diagnostic imaging, Lung Diseases, Fungal diagnostic imaging, Tomography, X-Ray Computed
- Abstract
Background: Computed tomography (CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which is an early sign of invasive pulmonary aspergillosis (IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life-threatening infection., Methods: Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings., Results: At presentation, most patients (94%) had > or =1 macronodules, and many (61%) also had halo signs. Other imaging findings at presentation, including consolidations (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent signs (10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment (52% vs. 29%; P<.001) and greater survival to 84 days (71% vs. 53%; P<.01) than did patients who presented with other imaging findings., Conclusions: Most patients presented with a halo sign and/or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival.
- Published
- 2007
- Full Text
- View/download PDF
7. 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.
- Author
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Patterson TF, Boucher HW, Herbrecht R, Denning DW, Lortholary O, Ribaud P, Rubin RH, Wingard JR, DePauw B, Schlamm HT, Troke P, and Bennett JE
- Subjects
- Drug Combinations, Humans, Itraconazole therapeutic use, Salvage Therapy, Treatment Outcome, Voriconazole, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Deoxycholic Acid therapeutic use, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
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.
- Published
- 2005
- Full Text
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8. Voriconazole treatment for less-common, emerging, or refractory fungal infections.
- Author
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Perfect JR, Marr KA, Walsh TJ, Greenberg RN, DuPont B, de la Torre-Cisneros J, Just-Nübling G, Schlamm HT, Lutsar I, Espinel-Ingroff A, and Johnson E
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- Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents adverse effects, Child, Humans, Middle Aged, Pyrimidines adverse effects, Treatment Outcome, Triazoles adverse effects, Voriconazole, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Candidiasis drug therapy, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections.
- Published
- 2003
- Full Text
- View/download PDF
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