Background. Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. Methods. Clinical data from patients with ...candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. Results. The incidence of candidemia caused by non–Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P=.002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. Conclusions. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.
Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this ...study was to evaluate factors associated with mortality in transplant patients with IA. Methods. Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. Results. Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 57.5% of 415) than in SOT patients (78 34.4% of 227; ). Independent poor P < .001 prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. Conclusions. There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.
Summary Objectives The study investigated the epidemiology and outcome of invasive aspergillosis (IA), an important cause of morbidity and mortality in immunocompromised patients. Methods Cases of ...proven/probable IA from the Prospective Antifungal Therapy Alliance (PATH Alliance® ) registry – a prospective surveillance network comprising 25 centers in the United States and Canada that collected data on invasive fungal infections from 2004 to 2008 – were analyzed with respect to clinical outcome. Results Nine hundred and sixty patients with IA were enrolled, the most frequent underlying disease being hematologic malignancy ( n = 464 48.3%). Two hundred and eighty patients (29.2%) received solid organ transplant; 268 patients (27.9%) underwent hematopoietic stem cell transplantation. Identified isolates included Aspergillus fumigatus (72.6%), Aspergillus flavus (9.9%), Aspergillus niger (8.7%) and Aspergillus terreus (4.3%). The lung was most frequently affected. Following diagnosis, 47% patients received monotherapy – voriconazole (70%), an amphotericin B formulation (13.8%), or an echinocandin (10.5%) – while 279 patients (29%) received combination therapy. Twelve-week overall survival was 64.4%. Conclusions In this series of patients with IA, the lung was the predominant focus of infection, A. fumigatus was the major species isolated, and overall survival appeared slightly improved compared with previous reports.
We sought the reservoir of Fusarium species in a hospital with cases of known fusarial infections. Cultures of samples from patients and the environment were performed and evaluated for relatedness ...by use of molecular methods. Fusarium species was recovered from 162 (57%) of 283 water system samples. Of 92 sink drains tested, 72 (88%) yielded Fusarium solani; 12 (16%) of 71 sink faucet aerators and 2 (8%) of 26 shower heads yielded Fusarium oxysporum. Fusarium solani was isolated from the hospital water tank. Aerosolization of Fusarium species was documented after running the showers. Molecular biotyping revealed multiple distinct genotypes among the isolates from the environment and patients. Eight of 20 patients with F. solani infections had isolates with a molecular match with either an environmental isolate (n = 2) or another patient isolate (n = 6). The time interval between the 2 matched patient-environment isolates pairs was 5 and 11 months, and 2, 4, and 5.5 years for the 3 patient-patient isolate pairs. The water distribution system of a hospital was identified as a reservoir of Fusarium species.
High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results ...in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity.
The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy.
A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m
by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients.
A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R
= 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R
= 0.99; p < 0.01).
The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.
Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of ...infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period.
To compare usual care with a home-based individualized exercise program (HBIEP) in patients receiving intensive treatment for multiple myeloma (MM)and epoetin alfa therapy.
Randomized trial with ...repeated measures of two groups (one experimental and one control) and an approximate 15-week experimental period.
Outpatient setting of the Myeloma Institute for Research and Therapy at the Rockfellow Cancer Center at the University of Arkansas for Medical Sciences.
187 patients with newly diagnosed MM enrolled in a separate study evaluating effectiveness of the Total Therapy regimen, with or without thalidomide.
Measurements included the Profile of Mood States fatigue scale, Functional Assessment of Cancer Therapy-Fatigue, ActiGraph® recordings, 6-Minute Walk Test, and hemoglobin levels at baseline and before and after stem cell collection. Descriptive statistics were used to compare demographics and treatment effects, and repeated measures analysis of variance was used to determine effects of HBIEP.
Fatigue, nighttime sleep, performance (aerobic capacity) as dependent or outcome measures, and HBIEP combining strength building and aerobic exercise as the independent variable.
Both groups were equivalent for age, gender, race, receipt of thalidomide, hemoglobin levels, and type of treatment regimen for MM. No statistically significant differences existed among the experimental and control groups for fatigue, sleep, or performance (aerobic capacity). Statistically significant differences (p < 0.05) were found in each of the study outcomes for all patients as treatment progressed and patients experienced more fatigue and poorer nighttime sleep and performance (aerobic capacity).
The effect of exercise seemed to be minimal on decreasing fatigue, improving sleep, and improving performance (aerobic capacity).
Exercise is safe and has physiologic benefits for patients undergoing MM treatment; exercise combined with epoetin alfa helped alleviate anemia.
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