Cytokine response as a biomarker for early diagnosis and outcome prediction of stem cell transplant recipients and acute leukemia patients with invasive aspergillosis.

We aimed to determine the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome prediction in hematologic patients. In this multicenter study, serum cytokines (IL6, IL10, INF-gamma, IL12, IL4, TNF-alpha, IL17, and IL23) were prospectively recruited from all consecutive patients with hematologic malignances at IA diagnosis and compared to control patients matched by center, age, baseline disease, and therapeutic regimen. We included 36 patients with IA and 36 controls. Serum levels of IL6 and IL10 cytokines on day 0 were significantly increased in patients with IA when compared to controls (P = 0.001 and P = 0.025, respectively), even in those who were neutropenic. No differences were observed for the other cytokines. IL6 and IL10 predicted IA with an area under the ROC curve of 0.74 (95% CI 0.62-0.86) and 0.64 (95% CI 0.51-0.77), respectively. The best cutoff point in predicting IA was 20.85 pg/ml for IL6 (sensitivity 72.2%; specificity 77.8%; PPV 76.5% and NPV 73.7%), and 0.045 pg/ml for IL10 (sensitivity 62.9%; specificity 63.9%; PPV 62.9% and NPV 63.9%). IL6 levels were associated with increased mortality, with the best cutoff value being 65.59 pg/ml in mortality prediction. In conclusion, in addition to current tests in place, IL6 and IL10 levels-as measured in plasma-may help clinicians diagnose IA. High levels of IL6 at IA diagnosis are related with worse outcomes. LAY SUMMARY: We evaluated the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome. Serum levels of IL6 and IL10 are increased in patients with IA compared to controls, and IL6 levels are associated with mortality.

Usefulness of guideline recommendations for prognosis in patients with candidemia.

We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.

[Epidemiology and prevention of nosocomial invasive infections by filamentous fungi and yeasts]. / Epidemiología y prevención de las infecciones nosocomiales causadas por especies de hongos filamentosos y levaduras.

Knowledge of the epidemiology of invasive fungal diseases in health care settings helps to establish the action levels necessary for its prevention. A first step is to identify groups of patients at high risk of invasive fungal diseases, establish accurate risk factors, observing the periods of greatest risk, and analyze the epidemiological profile in genera and species, as well as the patterns of antifungal resistance. Secondly, mechanisms to avoid persistent exposure to potential fungal pathogens must be established, protecting areas and recommending measures, such as the control of the quality of the air and water inside and outside the hospital, and determining and promoting appropriate architectural designs of health institutions. Finally, apart from the correct implementation of these measures, the use of antifungal prophylaxis should be considered in selected patients at very high risk, following the guidelines published.

Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study.

Pneumonia is a common cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) but updated and prospective information is partial. The aim of this nationwide prospective study is to determine the current epidemiology, etiology, and outcome of pneumonia in allo-HSCT recipients. From September-2003 to November-2005, 112 episodes in 427 consecutive allo-HSCT recipients were included (incidence 52.2 per 100 allo-HSCT/yr), and 72 of them (64.3%) were microbiologically defined pneumonia. Bacterial pneumonia (44.4%) was more frequent than fungal (29.2%) and viral pneumonia (19.4%). The most frequent microorganisms in each group were: Escherichia coli (n = 7, 8.9%), Streptococcus pneumoniae (n = 4, 5.0%), cytomegalovirus (n = 12, 15.4%), and Aspergillus spp. (n = 12, 15.4%). The development of pneumonia and chronic graft-versus-host disease (GVHD) was associated with increased mortality after allo-HSCT, and the probability of survival was significantly lower in patients that had at least one pneumonia episode (p < 0.01). Pneumonia development in the first 100 d after transplantation, fungal etiology, GVHD, acute respiratory failure, and septic shock were associated with increased mortality after pneumonia. Our results show that pneumonia remains a frequent infectious complication after allo-HSCT, contributing to significant mortality, and provide a large current experience with the incidence, etiology and outcome of pneumonia in these patients.

Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis.

Six of 284 patients treated with infliximab developed active tuberculosis. Four (67%) of these patients had a paradoxical response to antituberculous therapy. Physicians should be aware of the increased risk of a paradoxical response in this population and should consider the use of corticosteroids when a paradoxical reaction is suspected.