23 results on '"Schlamm, Haran T"'
Search Results
2. Good Outcomes in Therapy of Fusariosis Depend on Both an Effective Drug and the Host.
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Winston, Drew J, Young, Patricia A, Schlamm, Haran T, and Schiller, Gary J
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ANTIFUNGAL agents ,SALVAGE therapy ,NEUTROPHILS ,INVESTIGATIONAL drugs ,TREATMENT effectiveness ,ORAL drug administration ,LEUKEMIA ,CONVALESCENCE ,DERMATOMYCOSES - Published
- 2024
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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 ...
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Herbrecht, Raoul, Patterson, Thomas F., Slavin, Monica A., Marchetti, Oscar, Maertens, Johan, Johnson, Elizabeth M., Schlamm, Haran T., Donnelly, J. Peter, and Pappas, Peter G.
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ASPERGILLOSIS treatment ,VORICONAZOLE ,AMPHOTERICIN B ,COMMUNICABLE disease treatment ,MYCOSES ,DRUG efficacy ,COMPARATIVE studies ,THERAPEUTICS - Abstract
Episodes of invasive aspergillosis (IA) recruited to the voriconazole trial were reclassified according to the revised EORTC/MSG definitions. The efficacy of voriconazole was confirmed for possible, probable, and proven IA and was still better than found for the comparator arm.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. [ABSTRACT FROM PUBLISHER]
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- 2015
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4. Combination antifungal therapy for invasive aspergillosis: a randomized trial.
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Marr, Kieren A, Schlamm, Haran T, Herbrecht, Raoul, Rottinghaus, Scott T, Bow, Eric J, Cornely, Oliver A, Heinz, Werner J, Jagannatha, Shyla, Koh, Liang Piu, Kontoyiannis, Dimitrios P, Lee, Dong-Gun, Nucci, Marcio, Pappas, Peter G, Slavin, Monica A, Queiroz-Telles, Flavio, Selleslag, Dominik, Walsh, Thomas J, Wingard, John R, and Maertens, Johan A
- Abstract
Background: Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy.Objective: To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA.Design: Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479).Setting: 93 international sites.Patients: 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed.Measurements: The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures.Results: Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2 percentage points [95% CI, -19.0 to 1.5]; P = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different.Limitations: Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability.Conclusion: Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority.Primary Funding Source: Pfizer. [ABSTRACT FROM AUTHOR]- Published
- 2015
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5. Combination Antifungal Therapy for Invasive Aspergillosis.
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Marr, Kieren A., Schlamm, Haran T., Herbrecht, Raoul, Rottinghaus, Scott T., Bow, Eric J., Cornely, Oliver A., Heinz, Werner J., Jagannatha, Shyla, Liang Piu Koh, Kontoyiannis, Dimitrios P., Dong-Gun Lee, Nucci, Marcio, Pappas, Peter G., Slavin, Monica A., Queiroz-Telles, Flavio, Selleslag, Dominik, Walsh, Thomas J., Wingard, John R., and Maertens, Johan A.
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ANTIFUNGAL agents ,ASPERGILLOSIS treatment ,HEMATOLOGIC malignancies ,VORICONAZOLE ,PLACEBOS ,GALACTOMANNANS ,RADIOGRAPHY ,THERAPEUTICS - Abstract
Background: Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. Objective: To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. Design: Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479) Setting: 93 international sites. Patients: 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed. Measurements: The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures. Results: Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, −8.2 percentage points [95% CI, −19.0 to 1.5]; P = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, −11.5 percentage points [CI, −22.7 to −0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different. Limitations: Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability. Conclusion: Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority. Primary Funding Source: Pfizer. [ABSTRACT FROM AUTHOR]
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- 2015
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6. Voriconazole or Amphotericin B as Primary Therapy Yields Distinct Early Serum Galactomannan Trends Related to Outcomes in Invasive Aspergillosis.
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Chai, Louis Yi Ann, Kullberg, Bart Jan, Earnest, Arul, Johnson, Elizabeth M., Teerenstra, Steven, Vonk, Alieke G., Schlamm, Haran T., Herbrecht, Raoul, Netea, Mihai G., and Troke, Peter F.
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GALACTOMANNANS ,BLOOD serum analysis ,AMPHOTERICIN B ,ASPERGILLOSIS ,INTRODUCED fungi ,ANTIFUNGAL agents ,CLINICAL trials ,THERAPEUTICS - Abstract
An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response. [ABSTRACT FROM AUTHOR]
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- 2014
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7. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America.
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Nucci, Marcio, Colombo, Arnaldo L., Petti, Marco, Magana, Martin, Abreu, Paula, Schlamm, Haran T., and Sanchez, Sonia P.
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CANDIDIASIS ,MORTALITY ,ABDOMINAL surgery - Abstract
Incidence and mortality of candidaemia/invasive candidiasis (C/ IC) is relatively high in Latin America versus North America and Europe. To assess efficacy and safety of intravenous ( IV) anidulafungin in Latin American adults with documented C/ IC. All patients in this open-label study received initial IV anidulafungin with optional step-down to oral voriconazole after 5 days; total treatment duration was 14-42 days. The primary endpoint was global response (clinical + microbiological response) at end of treatment ( EOT); missing/indeterminate responses were failures. The study enrolled 54 patients; 44 had confirmed C/ IC within 96 h before study entry and comprised the modified intent-to-treat population. Global response at EOT was 59.1% (95% CI: 44.6, 73.6), with 13 missing/indeterminate assessments. Thirty-day all-cause mortality was 43.1%. Fourteen patients (31.8%) were able to step-down to oral voriconazole; these patients had lower baseline acute physiological assessment and chronic health evaluation ( APACHE) II scores and were less likely to have solid tumours or previous abdominal surgery. Anidulafungin was generally well tolerated with few treatment-related adverse events. Anidulafungin was associated with relatively low response rates influenced by a high rate of missing/indeterminate assessments and mortality comparable to other recent candidaemia studies in Latin America. In a subset of patients with lower APACHE II scores, short-course anidulafungin followed by oral voriconazole was successful. [ABSTRACT FROM AUTHOR]
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- 2014
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8. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.
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Chai, Louis Y A, Netea, Mihai G, Tai, Bee Choo, Khin, Lay Wai, Vonk, Alieke G, Teo, Boon Wee, Schlamm, Haran T, Herbrecht, Raoul, Donnelly, J Peter, Troke, Peter F, and Kullberg, Bart-Jan
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- 2013
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9. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.
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Chai, Louis Y. A., Netea, Mihai G., Tai, Bee Choo, Khin, Lay Wai, Vonk, Alieke G., Teo, Boon Wee, Schlamm, Haran T., Herbrecht, Raoul, Donnelly, J. Peter, Troke, Peter F., and Kullberg, Bart-Jan
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CYTOKINES ,CELLULAR immunity ,AMPHOTERICIN B ,AMPHOTERICINS ,NEPHROTOXICOLOGY - Abstract
Objectives The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD). Patients and methods In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis. Results The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI. Conclusions In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury. [ABSTRACT FROM PUBLISHER]
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- 2013
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10. Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes.
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Baddley, John W., Stephens, Jennifer M., Xiang Ji, Xin Gao, Schlamm, Haran T., and Tarallo, Miriam
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INTENSIVE care patients ,ASPERGILLOSIS ,PATIENTS ,CANCER risk factors ,NEUTROPENIA ,HIV infection risk factors ,ECONOMIC history - Abstract
Background: Few data are available regarding the epidemiology of invasive aspergillosis (IA) in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs) among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection. Methods: Retrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005- 2008). Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6) who received initial antifungal therapy (AF) in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS) were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models. Results: From 6,424 aspergillosis patients in the database, 412 (6.4%) ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%), acute respiratory failure (76%) and acute renal failure (41%). In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once). Mean length of stay (LOS) was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p < 0.0001 for both). Conclusions: Invasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation.
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Marks, David I., Pagliuca, Antonio, Kibbler, Christopher C., Glasmacher, Axel, Heussel, Claus-Peter, Kantecki, Michal, Miller, Paul J.S., Ribaud, Patricia, Schlamm, Haran T., Solano, Carlos, and Cook, Gordon
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ANTIFUNGAL agents ,HEMATOMA ,DRUG efficacy ,STEM cell transplantation ,MOLDS (Fungi) ,YEAST fungi - Abstract
Summary Antifungal prophylaxis for allogeneic haematopoietic stem-cell transplant (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs) and be well tolerated. This prospective, randomized, open-label, multicentre study compared the efficacy and safety of voriconazole (234 patients) versus itraconazole (255 patients) in alloHCT recipients. The primary composite endpoint, success of prophylaxis, incorporated ability to tolerate study drug for ≥100 d (with ≤14 d interruption) with survival to day 180 without proven/probable IFI. Success of prophylaxis was significantly higher with voriconazole than itraconazole (48·7% vs. 33·2%, P < 0·01); more voriconazole patients tolerated prophylaxis for 100 d (53·6% vs. 39·0%, P < 0·01; median total duration 96 vs. 68 d). The most common (>10%) treatment-related adverse events were vomiting (16·6%), nausea (15·8%) and diarrhoea (10·4%) for itraconazole, and hepatotoxicity/liver function abnormality (12·9%) for voriconazole. More itraconazole patients received other systemic antifungals (41·9% vs. 29·9%, P < 0·01). There was no difference in incidence of proven/probable IFI (1·3% vs. 2·1%) or survival to day 180 (81·9% vs. 80·9%) for voriconazole and itraconazole respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis after alloHCT, based on differences in the primary composite endpoint. Voriconazole could be given for significantly longer durations, with less need for other systemic antifungals. [ABSTRACT FROM AUTHOR]
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- 2011
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12. Ocular Manifestations of Candidemia.
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Lashof, Astrid M. L. Oude, Rothova, Aniki, Sobel, Jack D., Ruhnke, Markus, Pappas, Peter G., Viscoli, Claudio, Schlamm, Haran T., Oborska, Iwona T., Rex, John H., and Kullberg, Bart Jan
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CANDIDIASIS treatment ,OCULAR manifestations of general diseases ,AMPHOTERICIN B ,OPHTHALMOSCOPY ,RANDOMIZED controlled trials - 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. [ABSTRACT FROM AUTHOR]
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- 2011
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13. Early Proinflammatory Cytokines and C-Reactive Protein Trends as Predictors of Outcome in Invasive Aspergillosis.
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Chai, Louis Y. A., Netea, Mihai G., Teerenstra, Steven, Earnest, Arul, Vonk, Alieke G., Schlamm, Haran T., Herbrecht, Raoul, Troke, Peter F., and Kullberg, Bart-Jan
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C-reactive protein ,CYTOKINES ,ASPERGILLOSIS ,IMMUNE response ,INTERLEUKINS ,ANTIFUNGAL agents - Abstract
Background. Monitoring treatment response in invasive aspergillosis is challenging, because an immunocompromised host may not exhibit reliable symptoms and clinical signs. Cytokines play a pivotal role in mediating host immune response to infection; therefore, the profiling of biomarkers may be an appropriate surrogate for disease status. Methods. We studied, in a cohort of 119 patients with invasive aspergillosis who were recruited in a multicenter clinical trial, serum interleukin (IL)-6, IL-8, IL-10, interferon-g, and C-reactive protein (CRP) trends over the first 4 weeks of therapy and correlated these trends to clinical outcome parameters. Results. Circulating IL-6 and CRP levels were high at initiation of therapy and generally showed a downward trend with antifungal treatment. However, subjects with adverse outcomes exhibited a distinct lack of decline in IL-6 and CRP levels at week 1, compared with responders (Pp.02, for both IL-6 and CRP). Nonresponders also had significantly elevated IL-8 levels (P=.001). Conclusions. High initial IL-8 and persistently elevated IL-6, IL-8, and CRP levels after initiation of treatment may be early predictors of adverse outcome in invasive aspergillosis. Cytokine and CRP profiles could be used for early identification of patients with a poor response to antifungal treatment who may benefit from more-aggressive antimicrobial regimens. [ABSTRACT FROM AUTHOR]
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- 2010
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14. Changes in Causes of Death Over Time After Treatment for Invasive Aspergillosis.
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Wingard, John R., Ribaud, Patricia, Schlamm, Haran T., and Herbrecht, Raoul
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DEATH ,ASPERGILLOSIS treatment ,PATIENTS ,AMPHOTERICIN B ,MYCOSES - Abstract
The article discusses the results of a clinical study that was conducted to investigate the causes of death among patients who undergone treatment for invasive aspergillosis (IA). Of the total 277 patients participated, 98 died during the 12-week course of the study. It mentions that voriconazole was assigned to 144 patients while amphotericin B was recieved by the remaining 133 patients.
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- 2008
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15. An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis.
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Queiroz-Telles, Flavio, Goldani, Luciano Z., Schlamm, Haran T., Goodrich, James M., Espinel-Ingroff, Ana, and Shikanai-Yasuda, Maria A.
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TRIAZOLES ,ANTIFUNGAL agents ,DRUG efficacy ,PARACOCCIDIOIDOMYCOSIS ,SYSTEMIC mycoses ,THERAPEUTICS ,LIVER function tests ,CLINICAL trials - 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 ⩾1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed ⩾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. [ABSTRACT FROM AUTHOR]
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- 2007
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16. Imaging Findings in Acute Invasive Pulmonary Aspergillosis: Clinical Significance of the Halo Sign.
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Greene, Reginald E., Schlamm, Haran T., Oestmann, Jörg-W., Stark, Paul, Durand, Christine, Lortholary, Olivier, Wingard, John R., Herbrecht, Raoul, Ribaud, Patricia, Patterson, Thomas F., Troke, Peter F., Denning, David W., Bennett, John E., de Pauw, Ben E., and Rubin, Robert H.
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MEDICAL imaging systems ,PULMONARY aspergillosis ,TOMOGRAPHY ,ANTIFUNGAL agents ,MEDICAL radiography ,ASPERGILLOSIS - 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 ⩾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. [ABSTRACT FROM AUTHOR]
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- 2007
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17. 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.
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Patterson, Thomas F., Boucher, Helen W., Herbrecht, Raoul, Denning, David W., Lortholary, Olivier, Ribaud, Patricia, Rubin, Robert H., Wingard, John R., DePauw, Ben, Schlamm, Haran T., Troke, Peter, and Bennett, John E.
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ASPERGILLOSIS ,THERAPEUTICS ,AMPHOTERICIN B ,CLINICAL trials ,MYCOSES ,LIPIDS - 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 [3 6%] 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. [ABSTRACT FROM AUTHOR]
- Published
- 2005
18. Voriconazole Treatment for Less-Common, Emerging, or Refractory Fungal Infections.
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Perfect, John R., Marr, Kieren A., Walsh, Thomas J., Greenberg, Richard N., DuPont, Bertrand, de la Torre-Cisneros, Juliàn, Just-Nübling, Gudrun, Schlamm, Haran T., Lutsar, Irja, Espinel-Ingroff, Ana, and Johnson, Elizabeth
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MYCOSES ,THERAPEUTICS ,CANDIDIASIS ,ASPERGILLOSIS - 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 504570360f the overall cohort; specifically, successful outcomes were observed in 4760303560f patients whose infections failed to respond to previous antifungal therapy and in 6860303210f 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 0.000000or aspergillosis, 57.5 0.000000or candidiasis, 38.9 0.000000or cryptococcosis, 45.5 0.000000or fusariosis, and 30 0.000000or scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for < 1060304100f patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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19. Nutritional and metabolic assessment of the hospitalized patient.
- Author
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Blackburn, George L, Bistrian, Bruce R., Maini, Baltej S., Schlamm, Haran T., Smith, Michael F., Blackburn, G L, Bistrian, B R, Maini, B S, Schlamm, H T, and Smith, M F
- Published
- 1977
- Full Text
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20. Clinical effectiveness of a pancreatic enzyme supplement.
- Author
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Valerio, David, Whyte, Eric H.A., Schlamm, Haran T., Ruggiero, John A., Blackburn, George L., Valerio, D, Whyte, E H, Schlamm, H T, Ruggiero, J A, and Blackburn, G L
- Published
- 1981
- Full Text
- View/download PDF
21. Authors' response: Echinocandins -- first line in invasive candidiasis: how strong is this 'strong' evidence?
- Author
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Kett, Daniel H., Reboli, Annette C., Shorr, Andrew F., and Schlamm, Haran T.
- Subjects
CANDIDIASIS ,LETTERS to the editor - Abstract
A response from the author of the article "Echinocandins: First Line in Invasive Candidiasis: How Strong is This 'Strong' Evidence?" in a previous 2012 issue is presented.
- Published
- 2011
22. Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes.
- Author
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Baddley, John W, Stephens, Jennifer M, Ji, Xiang, Gao, Xin, Schlamm, Haran T, and Tarallo, Miriam
- Abstract
Background: Few data are available regarding the epidemiology of invasive aspergillosis (IA) in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs) among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection.Methods: Retrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005-2008). Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6) who received initial antifungal therapy (AF) in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS) were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models.Results: From 6,424 aspergillosis patients in the database, 412 (6.4%) ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%), acute respiratory failure (76%) and acute renal failure (41%). In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once). Mean length of stay (LOS) was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p < 0.0001 for both).Conclusions: Invasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients. [ABSTRACT FROM AUTHOR]- Published
- 2013
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23. Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: support for the 2009 IDSA treatment guidelines for candidiasis.
- Author
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Kett DH, Shorr AF, Reboli AC, Reisman AL, Biswas P, Schlamm HT, Kett, Daniel H, Shorr, Andrew F, Reboli, Annette C, Reisman, Arlene L, Biswas, Pinaki, and Schlamm, Haran T
- Abstract
Introduction: During the past decade, the incidence of Candida infections in hospitalized patients has increased, with fluconazole being the most commonly prescribed systemic antifungal agent for these infections. However, the 2009 Infectious Diseases Society of America (IDSA) candidiasis guidelines recommend an echinocandin for the treatment of candidemia/invasive candidiasis in patients who are considered to be "moderately severe or severely" ill. To validate these guidelines, clinical trial data were reviewed.Methods: A secondary analysis of data from a previously published prospective, randomized, double-blind clinical trial was performed; it compared anidulafungin with fluconazole for the treatment of invasive candidiasis and candidemia. Patients with critical illness were identified at study entry by using the following criteria: Acute Physiology and Chronic Health Evaluation (APACHE) II score of ≥ 15, evidence of severe sepsis (sepsis and one or more end-organ dysfunctions) present, and/or patient was in intensive care. Global response rates were compared at the end of intravenous study treatment (the primary end point of the original study) and all-cause mortality at 14 and 28 days from study entry in this group.Results: The patients (163 (66.5%) of 245) fulfilled at least one criterion for critical illness (anidulafungin, n = 89; fluconazole, n = 74). No significant differences were found in baseline characteristics between the two treatment groups. The global response rate was 70.8% for anidulafungin and 54.1% for fluconazole (P = 0.03; 95% confidence interval (CI): 2.0 to 31.5); all-cause mortality was 10.1% versus 20.3% at 14 days (P = 0.08; 95% CI, -0.9 to 21.3) and was 20.2% versus 24.3% at 28 days (P = 0.57; 95% CI, -8.8 to 17.0) for anidulafungin and fluconazole, respectively.Conclusions: In this post hoc analysis, anidulafungin was more effective than fluconazole for treatment of severely ill patients with candidemia, thus supporting the 2009 IDSA guidelines.Trial Registration: Clinicaltrials.gov NCT00058682. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
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