24 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
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- 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.)
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- 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.
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Herbrecht R, Patterson TF, Slavin MA, Marchetti O, Maertens J, Johnson EM, Schlamm HT, Donnelly JP, and Pappas PG
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- 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
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4. Combination antifungal therapy for invasive aspergillosis: a randomized trial.
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Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, Heinz WJ, Jagannatha S, Koh LP, Kontoyiannis DP, Lee DG, Nucci M, Pappas PG, Slavin MA, Queiroz-Telles F, Selleslag D, Walsh TJ, Wingard JR, and Maertens JA
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- Adolescent, Adult, Aged, Aged, 80 and over, Anidulafungin, Antifungal Agents adverse effects, Aspergillosis complications, Aspergillosis diagnosis, Aspergillosis mortality, Double-Blind Method, Drug Therapy, Combination, Echinocandins adverse effects, Female, Galactose analogs & derivatives, Hematologic Neoplasms therapy, Humans, Karnofsky Performance Status, Male, Mannans blood, Middle Aged, Platelet Count, Treatment Outcome, Voriconazole adverse effects, Young Adult, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Echinocandins therapeutic use, Hematologic Neoplasms complications, Hematopoietic Stem Cell Transplantation, Voriconazole therapeutic use
- 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.
- Published
- 2015
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5. Voriconazole or amphotericin B as primary therapy yields distinct early serum galactomannan trends related to outcomes in invasive aspergillosis.
- Author
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Chai LY, Kullberg BJ, Earnest A, Johnson EM, Teerenstra S, Vonk AG, Schlamm HT, Herbrecht R, Netea MG, and Troke PF
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- Aspergillosis diagnosis, Aspergillosis microbiology, Aspergillosis mortality, Biomarkers blood, Female, Galactose analogs & derivatives, Hematologic Neoplasms diagnosis, Hematologic Neoplasms drug therapy, Hematologic Neoplasms microbiology, Hematologic Neoplasms mortality, Humans, Male, Survival Analysis, Treatment Outcome, Voriconazole, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Fungal Polysaccharides blood, Mannans blood, Pyrimidines therapeutic use, Triazoles therapeutic use
- 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.
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- 2014
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6. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America.
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Nucci M, Colombo AL, Petti M, Magana M, Abreu P, Schlamm HT, and Sanchez SP
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- Adolescent, Adult, Aged, Aged, 80 and over, Anidulafungin, Female, Humans, Latin America, Male, Middle Aged, Treatment Outcome, Voriconazole, Young Adult, Antifungal Agents administration & dosage, Candidiasis, Invasive drug therapy, Echinocandins administration & dosage, Pyrimidines administration & dosage, Triazoles administration & dosage
- 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., (© 2013 Blackwell Verlag GmbH.)
- Published
- 2014
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7. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.
- Author
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Chai LY, Netea MG, Tai BC, Khin LW, Vonk AG, Teo BW, Schlamm HT, Herbrecht R, Donnelly JP, Troke PF, and Kullberg BJ
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- Adult, Aged, Amphotericin B administration & dosage, Antifungal Agents administration & dosage, Female, Humans, Male, Middle Aged, Serum chemistry, Acute Kidney Injury chemically induced, Acute Kidney Injury immunology, Amphotericin B adverse effects, Antifungal Agents adverse effects, Interleukin-10 blood, Interleukin-6 blood, Interleukin-8 blood
- 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.
- Published
- 2013
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8. Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes.
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Baddley JW, Stephens JM, Ji X, Gao X, Schlamm HT, and Tarallo M
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- Aged, Antifungal Agents economics, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Aspergillosis etiology, Female, Hospital Costs, Hospital Mortality, Humans, Length of Stay economics, Male, Middle Aged, Retrospective Studies, Aspergillosis economics, Aspergillosis epidemiology, Intensive Care Units economics
- 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.
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- 2013
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9. Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis.
- Author
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Chai LY, Kullberg BJ, Johnson EM, Teerenstra S, Khin LW, Vonk AG, Maertens J, Lortholary O, Donnelly PJ, Schlamm HT, Troke PF, Netea MG, and Herbrecht R
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- Female, Galactose analogs & derivatives, Humans, Invasive Pulmonary Aspergillosis drug therapy, Invasive Pulmonary Aspergillosis mortality, Male, Prognosis, ROC Curve, Survival Analysis, Time Factors, Treatment Outcome, Biomarkers blood, Drug Monitoring methods, Invasive Pulmonary Aspergillosis diagnosis, Mannans blood, Serum chemistry
- Abstract
The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥ 0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively; P = 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (n = 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (P = 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
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- 2012
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10. Tissue distribution of anidulafungin in neonatal rats.
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Ripp SL, Aram JA, Bowman CJ, Chmielewski G, Conte U, Cross DM, Gao H, Lewis EM, Lin J, Liu P, and Schlamm HT
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- Aging, Anidulafungin, Animals, Animals, Newborn, Dose-Response Relationship, Drug, Echinocandins administration & dosage, Echinocandins blood, Echinocandins pharmacology, Female, Male, Rats, Rats, Inbred F344, Time Factors, Tissue Distribution drug effects, Echinocandins pharmacokinetics
- Abstract
Anidulafungin, an echinocandin, is currently approved for treatment of fungal infections in adults. There is a high unmet medical need for treatment of fungal infections in neonatal patients, who may be at higher risk of infections involving bone, brain, and heart tissues. This in vivo preclinical study investigated anidulafungin distribution in plasma, bone, brain, and heart tissues in neonatal rats. Postnatal day (PND) 4 and PND 8 Fischer (F344/DuCrl) rats were dosed subcutaneously once with anidulafungin (10 mg/kg) or once daily for 5 days (PND 4-8). Plasma and tissue samples were collected and anidulafungin levels were measured by liquid chromatography-tandem mass spectrometry. The mean plasma Cmax and AUC0-24 values were consistent with single-dose plasma pharmacokinetics (dose normalized) reported previously for adult rats. Observed bone concentrations were similar to plasma concentrations regardless of dosing duration, with bone-to-plasma concentration ratios of approximately 1.0. Heart concentrations were higher than plasma, with heart to plasma concentration ratios of 1.3- to 1.8-fold. Brain concentrations were low after single dose, with brain-to-plasma concentration ratio of approximately 0.23, but increased to approximately 0.71 after 5 days of dosing. Tissue concentrations were nearly identical after single-dose administration in both PND 4 and PND 8 animals, indicating that anidulafungin does not appear to differentially distribute in this period in neonatal rats. In conclusion, anidulafungin distributes to bone, brain, and heart tissues of neonatal rats; such results are supportive of further investigation of efficacy against infections involving bone, brain, and heart tissues., (© 2012 Wiley Periodicals, Inc.)
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- 2012
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11. Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation.
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Marks DI, Pagliuca A, Kibbler CC, Glasmacher A, Heussel CP, Kantecki M, Miller PJ, Ribaud P, Schlamm HT, Solano C, and Cook G
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- Adolescent, Adult, Aged, Child, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Male, Middle Aged, Mycoses etiology, Prospective Studies, Transplantation, Homologous, Voriconazole, Young Adult, Antifungal Agents therapeutic use, Hematopoietic Stem Cell Transplantation methods, Itraconazole therapeutic use, Mycoses prevention & control, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
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., (2011 Blackwell Publishing Ltd.)
- Published
- 2011
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12. Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome.
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Reboli AC, Shorr AF, Rotstein C, Pappas PG, Kett DH, Schlamm HT, Reisman AL, Biswas P, and Walsh TJ
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- Anidulafungin, Candida albicans drug effects, Candidiasis, Invasive microbiology, Candidiasis, Invasive mortality, Candidiasis, Invasive pathology, Humans, Multivariate Analysis, Survival Analysis, Treatment Outcome, Antifungal Agents administration & dosage, Candida albicans isolation & purification, Candidiasis, Invasive drug therapy, Echinocandins administration & dosage, Fluconazole administration & dosage
- Abstract
Background: Candida albicans is the most common cause of candidemia and other forms of invasive candidiasis. Systemic infections due to C. albicans exhibit good susceptibility to fluconazole and echinocandins. However, the echinocandin anidulafungin was recently demonstrated to be more effective than fluconazole for systemic Candida infections in a randomized, double-blind trial among 245 patients. In that trial, most infections were caused by C. albicans, and all respective isolates were susceptible to randomized study drug. We sought to better understand the factors associated with the enhanced efficacy of anidulafungin and hypothesized that intrinsic properties of the antifungal agents contributed to the treatment differences., Methods: Global responses at end of intravenous study treatment in patients with C. albicans infection were compared post-hoc. Multivariate logistic regression analyses were performed to predict response and to adjust for differences in independent baseline characteristics. Analyses focused on time to negative blood cultures, persistent infection at end of intravenous study treatment, and 6-week survival., Results: In total, 135 patients with C. albicans infections were identified. Among these, baseline APACHE II scores were similar between treatment arms. In these patients, global response was significantly better for anidulafungin than fluconazole (81.1% vs 62.3%; 95% confidence interval [CI] for difference, 3.7-33.9). After adjusting for baseline characteristics, the odds ratio for global response was 2.36 (95% CI, 1.06-5.25). Study treatment and APACHE II score were significant predictors of outcome. The most predictive logistic regression model found that the odds ratio for study treatment was 2.60 (95% CI, 1.14-5.91) in favor of anidulafungin, and the odds ratio for APACHE II score was 0.935 (95% CI, 0.885-0.987), with poorer responses associated with higher baseline APACHE II scores. Anidulafungin was associated with significantly faster clearance of blood cultures (log-rank p < 0.05) and significantly fewer persistent infections (2.7% vs 13.1%; p < 0.05). Survival through 6 weeks did not differ between treatment groups., Conclusions: In patients with C. albicans infection, anidulafungin was more effective than fluconazole, with more rapid clearance of positive blood cultures. This suggests that the fungicidal activity of echinocandins may have important clinical implications., Trial Registration: ClinicalTrials.gov: NCT00058682., (© 2011 Reboli et al; licensee BioMed Central Ltd.)
- Published
- 2011
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13. Ocular manifestations of candidemia.
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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
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- 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.
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- 2011
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14. 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.
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Kett DH, Shorr AF, Reboli AC, Reisman AL, Biswas P, and Schlamm HT
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- Aged, Anidulafungin, Candidemia drug therapy, Candidemia mortality, Candidiasis, Invasive mortality, Double-Blind Method, Female, Humans, Male, Middle Aged, Practice Guidelines as Topic, Prospective Studies, Societies, Medical, Treatment Outcome, United States, Antifungal Agents therapeutic use, Candidiasis, Invasive drug therapy, Echinocandins therapeutic use, Fluconazole therapeutic use, Severity of Illness Index
- 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.
- Published
- 2011
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15. Early proinflammatory cytokines and C‐reactive protein trends as predictors of outcome in invasive Aspergillosis.
- Author
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Chai L, Netea MG, Teerenstra S, Earnest A, Vonk AG, Schlamm HT, Herbrecht R, Troke PF, and Kullberg BJ
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- Adult, Aged, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Aspergillosis pathology, Cohort Studies, Female, Humans, Male, Middle Aged, Prognosis, Treatment Outcome, Aspergillosis diagnosis, Aspergillosis immunology, C-Reactive Protein analysis, Cytokines blood
- 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‐γ, 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 (P = .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.
- Published
- 2010
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16. Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD).
- Author
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Luke DR, Tomaszewski K, Damle B, and Schlamm HT
- Subjects
- Animals, Antifungal Agents administration & dosage, Antifungal Agents chemistry, Antifungal Agents therapeutic use, Dogs, Excipients adverse effects, Excipients pharmacokinetics, Excipients toxicity, Humans, Pyrimidines administration & dosage, Pyrimidines chemistry, Pyrimidines therapeutic use, Rats, Triazoles administration & dosage, Triazoles chemistry, Triazoles therapeutic use, Voriconazole, beta-Cyclodextrins adverse effects, beta-Cyclodextrins pharmacokinetics, beta-Cyclodextrins toxicity, Excipients chemistry, beta-Cyclodextrins chemistry
- Abstract
Despite its use in commercially available drugs such as intravenous voriconazole, there is little known in the medical literature about the clinical pharmacology of the solubilizing agent, sulfobutylether-beta-cyclodextrin (SBECD). This paper summarizes all known data on SBECD pharmacokinetics and safety. In animals, volume of distribution approximates extracellular water volume and clearance is determined by the glomerular filtration rate. SBECD does not have any apparent effects on cardiovascular or respiratory systems, nor on autonomic and somatic functions in animals. In 1- and 6-month studies in rats and dogs, the most noteworthy findings were renal tubular vacuolation and foamy macrophages in the liver and lungs. Mild toxicity in the kidney and liver as a consequence of vacuolation occurred in rats at the maximum dose of 3000 mg/kg, which is approximately 50-fold greater than the SBECD dose typically administered in man. Doses up to 1500 mg/kg produced no histopathological evidence of toxicity in dog kidneys. SBECD has also been studied in healthy volunteers and subjects with renal dysfunction. Whereas plasma SBECD levels accumulate in those with renal compromise, there were no deleterious effects on renal function. Nonetheless, serum creatinine levels should be monitored in subjects with renal compromise receiving multiple doses of SBECD., ((c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2010
- Full Text
- View/download PDF
17. Changes in causes of death over time after treatment for invasive aspergillosis.
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Wingard JR, Ribaud P, Schlamm HT, and Herbrecht R
- Subjects
- Cause of Death, Humans, Survival Rate, Time Factors, Voriconazole, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Aspergillosis mortality, Graft vs Host Disease complications, Neoplasms complications, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
Background: Assessment of response to invasive aspergillosis (IA) therapy has been challenging in treatment trials., Methods: The causes of death over 12 weeks were categorized prospectively by a blinded data review committee using a priori defined criteria in participants in a randomized comparative trial of voriconazole versus amphotericin B as first-line therapy of proven or probable IA., Results: Death occurred in 98 of 277 patients during the 12-week course of study. Seventy-three of the 98 deaths (74%) occurred in the first 6 weeks; 25 deaths occurred during the second 6 weeks. Of the 73 deaths during the first 6 weeks, 50 (68%) were judged to be attributable to IA. Of the 25 deaths during the second 6 weeks, only 6 (24%) were judged to be attributable to IA. Fifty of the 56 deaths (89%) attributable to IA occurred during the first 6 weeks., Conclusions: These data suggest that most deaths due to IA occur during the first 6 weeks after the start of therapy and 6 weeks may be a better interval to judge the effectiveness of antifungal therapy because most deaths after 6 weeks are due to causes related to the underlying disease and its treatment rather than due to IA. Attributable mortality when assessed using a priori definitions and conducted in a blinded manner by a central data review committee can be useful in the assessment of IA therapy., ((c) 2008 American Cancer Society.)
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- 2008
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18. Comparative cost-effectiveness of voriconazole and amphotericin B in treatment of invasive pulmonary aspergillosis.
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Greene RE, Mauskopf J, Roberts CS, Zyczynski T, and Schlamm HT
- Subjects
- Amphotericin B therapeutic use, Aspergillosis drug therapy, Aspergillosis mortality, Cost-Benefit Analysis, Decision Trees, Humans, Lung Diseases, Fungal drug therapy, Lung Diseases, Fungal mortality, Pyrimidines therapeutic use, Survival Rate trends, Triazoles therapeutic use, Voriconazole, Amphotericin B economics, Aspergillosis economics, Lung Diseases, Fungal economics, Models, Economic, Pyrimidines economics, Triazoles economics
- Abstract
Purpose: The comparative cost-effectiveness of voriconazole and amphotericin B in the treatment of invasive pulmonary aspergillosis (IPA) was examined., Methods: A decision-tree model was constructed comparing 12-week treatment outcomes in a subset of patients enrolled in a clinical trial comparing initial treatment of IPA with amphotericin B versus voriconazole. Patients included those with IPA who underwent a thoracic computed tomographic (CT) scan at baseline. Cost and survival were estimated for those with and without a halo sign at baseline. Incremental cost-effectiveness ratios comparing voriconazole with amphotericin B were calculated for both patient subgroups., Results: Patients with a halo sign had similar costs and better survival rates than those without the sign. Within the subgroup of patients with the sign, total costs were lower and survival rates higher for those treated with voriconazole than for those treated with amphotericin B. For patients without a halo sign, total costs and survival rates were higher for those treated with voriconazole versus amphotericin B., Conclusion: Among patients treated for IPA, those with a baseline CT halo sign, an early indicator of the condition, appeared to have better survival rates and lower health care costs compared with patients without the sign. In patients with the halo sign, survival rates were higher and costs were lower when voriconazole rather than amphotericin B was used as first-line treatment; survival was better with voriconazole than with amphotericin B when the halo sign was not present. Voriconazole was cost-effective compared with amphotericin B when the halo sign was present, but voriconazole's cost-effectiveness when the sign was not present depended on the cost per life saved.
- Published
- 2007
- Full Text
- View/download PDF
19. An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis.
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Queiroz-Telles F, Goldani LZ, Schlamm HT, Goodrich JM, Espinel-Ingroff A, and Shikanai-Yasuda MA
- Subjects
- 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
- View/download PDF
20. Voriconazole as therapy for systemic Penicillium marneffei infections in AIDS patients.
- Author
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Supparatpinyo K and Schlamm HT
- Subjects
- AIDS-Related Opportunistic Infections microbiology, Acquired Immunodeficiency Syndrome microbiology, Adult, Female, Humans, Male, Mycoses microbiology, Mycoses virology, Voriconazole, AIDS-Related Opportunistic Infections drug therapy, Acquired Immunodeficiency Syndrome complications, Antifungal Agents therapeutic use, Mycoses complications, Mycoses drug therapy, Penicillium growth & development, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
The objective of this study was to evaluate the triazole anti-fungal agent, voriconazole, as therapy for systemic Penicillium marneffei infections in patients with advanced HIV infection. Patients with systemic P. marneffei infection were enrolled into a study of voriconazole for the treatment of less common, emerging, or refractory fungal infections. Patients were eligible for inclusion in the study on the basis that no anti-fungal agents have received regulatory approval specifically for P. marneffei infections. Patients were treated in the hospital setting with intravenous voriconazole (6 mg/kg every 12 hours on Day 1 and then 4 mg/kg every 12 hours for at least 3 days, after which patients could switch to oral therapy at 200 mg twice a day) or as outpatients with oral voriconazole (400 mg twice a day on Day 1 and then 200 mg twice a day) for a maximum of 12 weeks. Eleven patients received treatment with voriconazole. Two received short courses of intravenous therapy followed by the oral formulation; nine were treated with oral voriconazole only. At the end of therapy, eight of the nine evaluable patients had favorable response to therapy, based on mycological and clinical findings. There were no relapses of P. marneffei infection in the six patients who were seen at follow-up within 4 weeks of the end of therapy. Treatment with voriconazole was well tolerated, with no discontinuations caused by drug-related adverse events. The results of this study suggest that voriconazole is an effective, well-tolerated, and convenient option for the treatment of systemic infections with P. marneffei.
- Published
- 2007
21. 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
22. 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
- View/download PDF
23. 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
- Subjects
- 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
24. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.
- Author
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Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, and de Pauw B
- Subjects
- Adolescent, Adult, Aged, Amphotericin B adverse effects, Antifungal Agents adverse effects, Aspergillosis microbiology, Aspergillosis mortality, Female, Hematologic Diseases complications, Humans, Infusions, Intravenous, Male, Middle Aged, Pyrimidines adverse effects, Survival Rate, Triazoles adverse effects, Voriconazole, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
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., (Copyright 2002 Massachusetts Medical Society)
- Published
- 2002
- Full Text
- View/download PDF
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