Teresa Cardoso

A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients.

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.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes

IntroductionInvasive 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.MethodsAn 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.ResultsA 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.ConclusionsIA 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.

Additional risk factors for infection by multidrug-resistant pathogens in healthcare- associated infection: a large cohort study

BackgroundThere is a lack of consensus regarding the definition of risk factors for healthcare-associated infection (HCAI). The purpose of this study was to identify additional risk factors for HCAI, which are not included in the current definition of HCAI, associated with infection by multidrug-resistant (MDR) pathogens, in all hospitalized infected patients from the community.MethodsThis 1-year prospective cohort study included all patients with infection admitted to a large, tertiary care, university hospital. Risk factors not included in the HCAI definition, and independently associated with MDR pathogen infection, namely MDR Gram-negative (MDR-GN) and ESKAPE microorganisms (vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species, carbapenem-hydrolyzing Klebsiella pneumonia and MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), were identified by logistic regression among patients admitted from the community (either with community-acquired or HCAI).ResultsThere were 1035 patients with infection, 718 from the community. Of these, 439 (61%) had microbiologic documentation; 123 were MDR (28%). Among MDR: 104 (85%) had MDR-GN and 41 (33%) had an ESKAPE infection. Independent risk factors associated with MDR and MDR-GN infection were: age (adjusted odds ratio (OR) = 1.7 and 1.5, p = 0.001 and p = 0.009, respectively), and hospitalization in the previous year (between 4 and 12 months previously) (adjusted OR = 2.0 and 1,7, p = 0.008 and p = 0.048, respectively). Infection by pathogens from the ESKAPE group was independently associated with previous antibiotic therapy (adjusted OR = 7.2, p < 0.001) and a Karnofsky index <70 (adjusted OR = 3.7, p = 0.003). Patients with infection by MDR, MDR-GN and pathogens from the ESKAPE group had significantly higher rates of inadequate antibiotic therapy than those without (46% vs 7%, 44% vs 10%, 61% vs 15%, respectively, p < 0.001).ConclusionsThis study suggests that the inclusion of additional risk factors in the current definition of HCAI for MDR pathogen infection, namely age >60 years, Karnofsky index <70, hospitalization in the previous year, and previous antibiotic therapy, may be clinically beneficial for early diagnosis, which may decrease the rate of inadequate antibiotic therapy among these patients.

The Impact of Healthcare-Associated Infection on Mortality: Failure in Clinical Recognition Is Related with Inadequate Antibiotic Therapy

Purpose To understand if clinicians can tell apart patients with healthcare-associated infections (HCAI) from those with community-acquired infections (CAI) and to determine the impact of HCAI in the adequacy of initial antibiotic therapy and hospital mortality. Methods One-year prospective cohort study including all consecutive infected patients admitted to a large university tertiary care hospital. Results A total of 1035 patients were included in this study. There were 718 patients admitted from the community: 225 (31%) with HCAI and 493 (69%) with CAI. Total microbiologic documentation rate of infection was 68% (n = 703): 56% in CAI, 73% in HCAI and 83% in hospital-acquired infections (HAI). Antibiotic therapy was inadequate in 27% of patients with HCAI vs. 14% of patients with CAI (p<0.001). Among patients with HCAI, 47% received antibiotic therapy in accordance with international recommendations for treatment of CAI. Antibiotic therapy was inadequate in 36% of patients with HCAI whose treatment followed international recommendations for CAI vs. 19% in the group of HCAI patients whose treatment did not follow these guidelines (p = 0.014). Variables independently associated with inadequate antibiotic therapy were: decreased functional capacity (adjusted OR = 2.24), HCAI (adjusted OR = 2.09) and HAI (adjusted OR = 2.24). Variables independently associated with higher hospital mortality were: age (adjusted OR = 1.05, per year), severe sepsis (adjusted OR = 1.92), septic shock (adjusted OR = 8.13) and inadequate antibiotic therapy (adjusted OR = 1.99). Conclusions HCAI was associated with an increased rate of inadequate antibiotic therapy but not with a significant increase in hospital mortality. Clinicians need to be aware of healthcare-associated infections among the group of infected patients arriving from the community since the existing guidelines regarding antibiotic therapy do not apply to this group and they will otherwise receive inadequate antibiotic therapy which will have a negative impact on hospital outcome.

Predisposition, Insult/Infection, Response and Organ Dysfunction (PIRO): A Pilot Clinical Staging System for Hospital Mortality in Patients with Infection

Purpose To develop a clinical staging system based on the PIRO concept (Predisposition, Infection, Response and Organ dysfunction) for hospitalized patients with infection. Methods One year prospective cohort study of all hospitalized patients with infection (n = 1035), admitted into a large tertiary care, university hospital. Variables associated with hospital mortality were selected using logistic regressions. Based on the regression coefficients, a score for each PIRO component was developed and a classification tree was used to stratify patients into four stages of increased risk of hospital mortality. The final clinical staging system was then validated using an independent cohort (n = 186). Results Factors significantly associated with hospital mortality were • for Predisposition: age, sex, previous antibiotic therapy, chronic hepatic disease, chronic hematologic disease, cancer, atherosclerosis and a Karnofsky index<70; • for Insult/Infection: type of infection • for Response: abnormal temperature, tachypnea, hyperglycemia and severity of infection and • for Organ dysfunction: hypotension and SOFA score≥1. The area under the ROC curve (CI95%) for the combined PIRO model as a predictor for mortality was 0.85 (0.82–0.88). Based on the scores for each of the PIRO components and on the cut-offs estimated from the classification tree, patients were stratified into four stages of increased mortality rates: stage I: ≤5%, stage II: 6–20%, stage III: 21–50% and stage IV: >50%. Finally, this new clinical staging system was studied in a validation cohort, which provided similar results (0%, 9%, 31% and 67%, in each stage, respectively). Conclusions Based on the PIRO concept, a new clinical staging system was developed for hospitalized patients with infection, allowing stratification into four stages of increased mortality, using the different scores obtained in Predisposition, Response, Infection and Organ dysfunction. The proposed system will likely help to define inclusion criteria in clinical trials as well as tailoring individual management plans for patients with infection.

Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patients with COPD

Invasive pulmonary aspergillosis (IPA) is a potentially lethal opportunistic infection, mainly affecting immunocompromised patients, particularly those with prolonged neutropenia [1]. Several reports have shown that Aspergillus spp. can also cause IPA in patients with a priori less severe immune dysfunction, such as those in intensive care units (ICUs) [2–5] or with chronic obstructive pulmonary disease (COPD) [5–8]. In these patients, diagnosis of IPA remains a challenge, because the reference diagnostic criteria (defined by the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG)) were developed for research in high-risk patients and not specifically for patients in the ICU or patients with COPD [9]. Two alternative algorithms have been proposed for this setting: the COPD algorithm for patients with COPD [6] and the Clinical algorithm for patients in the ICU [10]. In ICU COPD patients, the Clinical algorithm seems to be more useful to diagnose IPA than the COPD or EORTC/MSG ones http://ow.ly/N2TN30e6Zur

The Role of Noninvasive Ventilation in Patients with "Do Not Intubate" Order in the Emergency Setting.

Background Noninvasive ventilation (NIV) is being used increasingly in patients who have a “do not intubate” (DNI) order. However, the impact of NIV on the clinical and health-related quality of life (HRQOL) in the emergency setting is not known, nor is its effectiveness for relieving symptoms in end-of-life care. Objective The aim of this prospective study was to determine the outcome and HRQOL impact of regular use of NIV outcomes on patients with a DNI order who were admitted to the emergency room department (ED). Methods: Eligible for participation were DNI-status patients who receive NIV for acute or acute-on-chronic respiratory failure when admitted to the ED of a tertiary care, university-affiliated, 600-bed hospital between January 2014 and December 2014. Patients were divided into 2 groups: (1) those whose DNI order related to a decision to withhold therapy and (2) those for whom any treatment, including NIV, was provided for symptom relief only. HRQOL was evaluated only in group 1, using the 12-item Short Form Health Survey (SF-12). Long-term outcome was evaluated 90 days after hospital discharge by means of a telephone interview. Results During the study period 1727 patients were admitted to the ED, 243 were submitted to NIV and 70 (29%) were included in the study. Twenty-nine (41%) of the 70 enrollees received NIV for symptom relief only (group2). Active cancer [7% vs 35%, p = 0,004] and neuromuscular diseases [0% vs. 17%] were more prevalent in this group. NIV was stopped in 59% of the patients in group 2 due to lake of clinical benefit. The in-hospital mortality rate was 37% for group 1 and 86% for group 2 0,001). Among patients who were discharged from hospital, 23% of the group 1 and all patients in group 2 died within 90 days. Relative to baseline, no significant decline in HRQOL occurred in group 1 by 90 days postdischarge. Conclusion The survival rate was 49% among DNI-status patients for whom NIV was used as a treatment in ED, and these patients did not experience a decline in HRQOL throughout the study. NIV did not provide significant relief of symptoms in more than half the patients who receive it for that purpose.

Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort

Data regarding the epidemiology and diagnosis of invasive aspergillosis in the critically ill population are limited, with data regarding elderly patients (≥75 years old) even scarcer. We aimed to further compare the epidemiology, characteristics and outcome of elderly versus nonelderly critically ill patients with invasive aspergillosis (IA) Prospective, international, multicenter observational study (AspICU) including adult intensive care unit (ICU) patients, with a culture and/or direct examination and/or histopathological sample positive for Aspergillus spp. at any site. We compared clinical characteristics and outcome of IA in ICU patients using two different diagnostic algorithms. Elderly and nonelderly ICU patients with IA differed in a number of characteristics, including comorbidities, clinical features of the disease, mycology testing, and radiological findings. No difference regarding mortality was found. According to the clinical algorithm, elderly patients were more likely to be diagnosed with putative IA. Elderly patients had less diagnostic radiological findings and when these findings were present they were detected late in the disease course. The comparison between elderly survivors and nonsurvivors demonstrated differences in clinical characteristics of the disease, affected sites and supportive therapy needed. All patients who were diagnosed with proven IA died. Increased vigilance combined with active search for mycological laboratory evidence and radiological confirmation are necessary for the timely diagnosis of IA in the elderly patient subset. Although elderly state per se is not a particular risk factor for mortality, a high SOFA score and the decision not to administer antifungal therapy may have an impact on survival of elderly patients.

Risk factors for long-term mortality in patients admitted with severe infection

BackgroundSevere infection is a main cause of mortality. We aim to describe risk factors for long-term mortality among inpatients with severe infection.MethodsProspective cohort study in a 600-bed university hospital in Portugal including all patients with severe infection admitted into intensive care, medical, surgical, hematology and nephrology wards over one-year period. The outcome of interest was 5-year mortality following infection. Variables of patient background and infectious episode were studied in association with the main outcome through multiple logistic regression. There were 1013 patients included in the study. Hospital and 5-year mortality rates were 14 and 37%, respectively.ResultsTwo different models were developed (with and without acute-illness severity scores) and factors independently associated with 5-year mortality were [adjusted odds ratio (95% confidence interval)]: age = 1.03 per year (1.02-1.04), cancer = 4.36 (1.65–11.53), no comorbidities = 0.4 (0.26–0.62), Karnovsky Index < 70 = 2.25 (1.48–3.40), SAPS (Simplified Acute Physiology Score) II = 1.05 per point (1.03–1.07), positive blood cultures = 1.57 (1.01–2.44) and infection by an ESKAPE pathogen (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeroginosa and Enterobacter species) = 1.61 (1.00– 2.60); and in the second model [without SAPS II and SOFA (Sequential Organ Failure Assessment) scores]: age = 1.04 per year (1.03–1.05), cancer = 5.93 (2.26–15.51), chronic haematologic disease = 2.37 (1.14–4.93), no comorbidities = 0.45 (0.29–0.69), Karnovsky Index< 70 = 2.32 (1.54– 3.50), septic shock [reference is infection without SIRS (Systemic Inflammatory Response Syndrome)] = 3.77 (1.80–7.89) and infection by an ESKAPE pathogen = 1.61 (1.00–2.60). Both models presented a good discrimination power with an AU-ROC curve (95% CI) of 0.81 (0.77–0.84) for model 1 and 0.80 (0.76–0.83) for model 2. If only patients that survived hospital admission are included in the model, variables retained are: age = 1.03 per year (1.02–1.05), cancer = 4.69 (1.71–12.83), chronic respiratory disease = 2.27 (1.09–4.69), diabetes mellitus = 1.65 (1.06–2.56), Karnovsky Index < 70 = 2.50 (1.63–3.83) and positive blood cultures = 1.66 (1.04–2.64) with an AU-ROC curve of 0.77 (0.73–0.81).ConclusionsAge, previous comorbidities, and functional status and infection by an ESKAPE pathogen were consistently associated with long-term prognosis. This information may help in the discussion of individual prognosis and clinical decision-making.

Eosinophilic pneumonia presenting as life-threatening ARDS

We present a case of a 25-year-old woman with sudden onset of shortness of breath, cough and malaise, 24 h after discharge from a psychiatric hospital. She had been there for 2 weeks after a suicide attempt with lye, and started treatment with paroxetin, alprazolam and valproic acid. She also started smoking 20 cigarettes/day during that hospital admission. Brought to the emergency department, she evolved in the first 24 h with respiratory failure and shock needing intensive care unit (ICU) admission, with mechanical ventilation and vasopressor support. Empiric antibiotic therapy was started (piperacillin-tazobactam and azithromycin) suspecting healthcare-associated pneumonia. The patients chest radiography progressed with bilateral infiltrates. Peripheral blood eosinophilia was seen on the second day. A bronchoalveolar lavage was performed and had 50% of eosinophils. She was started on treatment with steroids and the next day no longer needed vasopressors; 4 days later she was extubated.