Impact of Invasive Fungal Infections on Mortality, Length of Hospital Stay, and Costs in Allogeneic Hematopoietic Stem Cell Transplant Patients

Over the last decade, unrelated donors have become a vital resource for hematopoietic stem cell transplantation (HSCT) and the number of allogeneic HSCT (allo-HSCT) has increased significantly. While invasive fungal infections (IFIs) remain major concerns in these patients, data regarding impact of these infections on mortality, length of hospital stay, and hospital charge are limited in the United States at a national level. Additionally, with many updates in transplant practice, risk factors for IFIs in these patients may have changed

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

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 ar

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

<p>Abstract</p> <p>Background</p> <p><it>Candida albicans </it>is the most common cause of candidemia and other forms of invasive candidiasis. Systemic infections due to <it>C. albicans </it>exhibit good susceptibility to fluconazole and echinocandins. However, the echinocandin anidulafungin was recently demonstrated to be more effective than fluconazole for systemic <it>Candida </it>infections in a randomized, double-blind trial among 245 patients. In that trial, most infections were caused by <it>C. albicans</it>, 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.</p> <p>Methods</p> <p>Global responses at end of intravenous study treatment in patients with <it>C. albicans </it>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.</p> <p>Results</p> <p>In total, 135 patients with <it>C. albicans </it>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 <it>p </it>< 0.05) and significantly fewer persistent infections (2.7% vs 13.1%; <it>p </it>< 0.05). Survival through 6 weeks did not differ between treatment groups.</p> <p>Conclusions</p> <p>In patients with <it>C. albicans </it>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.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00058682">NCT00058682</a></p

Impact of Invasive Fungal Infections on Mortality, Length of Hospital Stay, and Costs in Allogeneic Hematopoietic Stem Cell Transplant Patients

Over the last decade, unrelated donors have become a vital resource for hematopoietic stem cell transplantation (HSCT) and the number of allogeneic HSCT (allo-HSCT) has increased significantly. While invasive fungal infections (IFIs) remain major concerns in these patients, data regarding impact of these infections on mortality, length of hospital stay, and hospital charge are limited in the United States at a national level. Additionally, with many updates in transplant practice, risk factors for IFIs in these patients may have changed

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

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.status: publishe