Pierre Bulpa

RATIONALE: The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. OBJECTIVES: We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. METHODS: We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n = 524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. MEASUREMENTS AND MAIN RESULTS: Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to have putative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). CONCLUSIONS: The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients.

Aspergillus spp. cultured in specimens from the airways of chronic obstructive pulmonary disease (COPD) patients are frequently considered as a contaminant. However, growing evidence suggests that severe COPD patients are at higher risk of developing invasive pulmonary aspergillosis (IPA), although IPA incidence in this population is poorly documented. Some data report that COPD is the underlying disease in 1% of patients with IPA. Definitive diagnosis of IPA in COPD patients is often difficult as tissue samples are rarely obtained before death. Diagnosis is therefore usually based on a combination of clinical features, radiological findings (mostly thoracic computed tomography scans), microbiological results and, sometimes, serological information. Of 56 patients with IPA reported in the literature, 43 (77%) were receiving corticosteroids on admission to hospital. Breathlessness was always a feature of disease and excess wheezing was present in 79% of patients. Fever (>38 degrees C) was present in only 38.5%. Chest pain and haemoptysis were uncommon. Six out of 33 (18%) patients had tracheobronchitis observed during bronchoscopy. The median delay between symptoms and diagnosis was 8.5 days. The mortality rate was high: 53 out of 56 (95%) patients died despite invasive ventilation and antifungal treatment in 43 (77%) of them. In chronic obstructive pulmonary disease patients, invasive pulmonary aspergillosis currently carries a very poor prognosis. Outcome could perhaps be improved by more rapid diagnosis and prompt therapy with voriconazole.

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting. METHODS: An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. RESULTS: A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis. CONCLUSIONS: IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.

OBJECTIVE: To evaluate the correlation between specific prognosis of hematologic malignancies on the one hand and intensive care unit and hospital mortality in critically ill patients with hematologic malignancies on the other hand. DESIGN: Observational study during a 10-yr period. SETTING: A 22-bed medical-surgical intensive care unit. PATIENTS: A total of 84 consecutive patients with nonterminal hematologic malignancies with medical complications requiring intensive care. INTERVENTIONS: None. MEASUREMENTS: Demographic factors, acute physiology and organ dysfunction scores, microbiology, therapeutic support, and hematologic factors data on admission and during the intensive care unit stay were collected, together with mortality follow-up. Based on specific-disease prognostic factors and related published survival curves, the prognosis of hematologic malignancies was assessed and defined as good, intermediate, or poor according to a 3-yr survival probability of >50%, 20-50%, or <20%, respectively. MAIN RESULTS: Prognosis of hematologic malignancies does not predict intensive care unit or hospital mortality and almost reaches significance for 6-mo mortality (53%, 71%, and 84% rate for patients with good, intermediate, and poor prognosis, respectively, p =.058), but it determines long-term survival (p =.008). Intensive care unit, hospital, and 6-mo overall mortality rates were 38%, 61%, and 75%, respectively. Using multivariate analysis, intensive care unit mortality was best predicted on admission by respiratory failure and fungal infection, whereas hospital mortality was predicted by the number of organ failures, the bone marrow transplant status, and the presence of fungal infection. The Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II had no prognostic value, whereas the difference of the Multiple Organ Dysfunction Score between at the time of admission and at day 5 allowed quick prediction of hospital mortality. Diseases with the poorest 6-mo prognosis were acute myeloid leukemia and non-Hodgkin lymphoma. CONCLUSION The severity of the underlying hematologic malignancies does not influence intensive care unit or hospital mortality. Short-term prognosis is exclusively predicted by acute organ dysfunctions and by a pathogen's aggressiveness. Therefore, reluctance to admit patients with nonterminal hematologic malignancies to the intensive care unit based only on the prognosis of their underlying hematologic malignancy does not seem justified.

Great differences in end-of-life practices in treating the critically ill around the world warrant agreement regarding the major ethical principles. This analysis determines the extent of worldwide consensus for end-of-life practices, delineates where there is and is not consensus, and analyzes reasons for lack of consensus. Critical care societies worldwide were invited to participate. Country coordinators were identified and draft statements were developed for major end-of-life issues and translated into six languages. Multidisciplinary responses using a web-based survey assessed agreement or disagreement with definitions and statements linked to anonymous demographic information. Consensus was prospectively defined as >80% agreement. Definitions and statements not obtaining consensus were revised based on comments of respondents, and then translated and redistributed. Of the initial 1,283 responses from 32 countries, consensus was found for 66 (81%) of the 81 definitions and statements; 26 (32%) had >90% agreement. With 83 additional responses to the original questionnaire (1,366 total) and 604 responses to the revised statements, consensus could be obtained for another 11 of the 15 statements. Consensus was obtained for informed consent, withholding and withdrawing life-sustaining treatment, legal requirements, intensive care unit therapies, cardiopulmonary resuscitation, shared decision making, medical and nursing consensus, brain death, and palliative care. Consensus was obtained for 77 of 81 (95%) statements. Worldwide consensus could be developed for the majority of definitions and statements about end-of-life practices. Statements achieving consensus provide standards of practice for end-of-life care; statements without consensus identify important areas for future research.