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Background: Assessing the outcome of patients with invasive pulmonary aspergillosis by using conventional criteria is difficult, particularly when clinical and radiologic worsening coincides with neutrophil recovery. Usually, it is assumed that this deterioration is related to progressive aspergillosis, prompting changes in patient management. However, its temporal relation with neutrophil recovery suggests that it may be caused by an immune reconstitution syndrome (IRIS). Galactomannan is an Aspergillus-specific polysaccharide that is released during aspergillosis and is detected by the serum galactomannan test, which has been approved by the United States Food and Drug Administration for the diagnosis of invasive aspergillosis. In this study, the authors used sequential galactomannan testing to distinguish IRIS responses from progressive aspergillosis., Methods: From April 2001 to December 2006, patients with hematologic malignancies underwent galactomannan screening during periods when they were at risk. The clinical and laboratory findings from patients who had >or=2 consecutive positive galactomannan assays (optical density, >or=0.5) were reviewed., Results: Nineteen neutropenic patients with aspergillosis developed clinical and radiologic pulmonary deterioration during neutrophil recovery. Deterioration coincided with microbiologic response, as documented by rapid normalization of serum galactomannan, and, in 16 patients, was followed by complete clinical response and survival at 3 months, although there were no changes in antifungal therapy. The 3 patients who died during the first month had no evidence of aspergillosis at autopsy examination., Conclusions: The authors propose that IRIS was responsible for the current findings and provide a definition for the syndrome. They also recommend serial galactomannan testing to guide aspergillosis management. Declining galactomannan values imply IRIS with an aspergillus response and obviate the need for invasive procedures and alternative antifungal therapies, whereas persistent galactomannan elevation indicates progressive aspergillosis and requires prompt treatment modification., (Copyright (c) 2007 American Cancer Society.)

The pharmacokinetics of posaconazole oral suspension in neutropenic patients undergoing high-dose chemotherapy and stem cell transplantation were evaluated, and the association of plasma posaconazole exposure with the presence and severity of oral mucositis was explored in this nonrandomized, open-label, parallel-group, multiple-dose pharmacokinetic study. Thirty patients were enrolled and received one of three regimens (group I, 200 mg once daily; group II, 400 mg once daily; group III, 200 mg four times daily) for the duration of neutropenia. The mean total exposure for day 1, as shown by the area under the concentration-time curve from 0 to 24 h (AUC(0-24)), was 1.96 mg . h/liter in group I and was 51% higher in group II and in group III. Increases in AUC(0-24) and maximum plasma concentration (C(max)) in groups II and III were dose related. The AUC(0-24) and C(max) values on day 1 were similar between groups II and III. There was interpatient variability of up to 68% in the pharmacokinetic values for our study population. Steady state was attained by days 5 to 6. Average steady-state plasma posaconazole trough values were 192, 219, and 414 ng/ml in groups I, II, and III, respectively. The AUC(0-24) and apparent oral clearance increased by increasing dose and dosing frequency. Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC and C(max)) at steady state (P = 0.1483). Moreover, this reduction could be overcome by increasing the total dose and dosing frequency. Posaconazole was safe and well tolerated.

Background. The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. Methods. The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. Results. We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versushost disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelvemonth cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matchedrelated allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. Conclusions. In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design. [ABSTRACT FROM AUTHOR]