Epidemiology,risk factors for and outcome of candidaemia among non‐neutropenic patients in a Greek intensive care unit

To determine the epidemiology, risk factors for and outcome of candidaemia in critically ill patients, a matched case–control study was performed in a 25‐bed intensive care unit (ICU) from August 2004 to January 2006. Candidaemia occurred in 33 patients; each patient was matched to four controls according to admission illness severity, diagnostic category and length of ICU stay. Candida non‐albicans species predominated (67.7%). The presence of acute respiratory distress syndrome (ARDS) was the only independent risk factor for candidaemia development (OR, 2.93; 95% CI 1.09–7.81, P = 0.032). Mortality was 60.6% among patients with candidaemia and 22% among controls (P < 0.001). The presence of candidaemia (OR, 9.37; 95% CI 3.48–25.26, P < 0.001) and the illness severity on admission (acute physiologic and chronic health evaluation II score, OR, 1.17; 95% CI 1.12–1.24, P < 0.001) were independently associated with mortality. Among candidaemic patients, risk factors for mortality were the severity of organ dysfunction (sequential organ failure assessment score, OR, 1.57; 95% CI 1.00–2.46, P = 0.05) and a low serum albumin level (OR, 0.74; 95% CI 0.59–0.94, P = 0.012) both of them occurred on candidaemia onset. We conclude that in critically ill patients matched for illness severity and length of ICU stay, the only independent risk factor for candidaemia was the presence of ARDS. Mortality was independently associated with acquisition of candidaemia and with the illness severity at candidaemia onset.     

A scoring model of factors associated with Candida glabrata candidemia among critically ill patients

Candida species, including Candida glabrata (CG), are common causes of bloodstream infections among intensive care unit (ICU) patients. Many CG isolates have decreased susceptibility to fluconazole. Constructing a scoring model of factors associated with CG candidemia in ICU patients that can be used if fluconazole susceptibility testing is not readily available. We identified patients with candidemia that were admitted to the ICU of the Mayo Clinic in Rochester, Minnesota from 1998 to 2006. Using patient demographical and clinical data abstracted via chart review, a multivariable logistic regression model was developed to distinguish those with CG candidemia. We identified 246 patients with candidemia including 68 CG cases. Multivariable analysis identified four independent factors associated with CG candidemia: absence of renal failure, less than 7 days in the hospital, abdominal surgery and fluconazole use. The predictive ability of the model, based on the c-statistic, was 0.727. In a large ICU cohort, a scoring model that included four risk factors, which are readily ascertainable at the bedside, was created to distinguish candidemia due to CG from other causes of candidemia. The identification of risk factors associated with CG candidemia could aid physicians in the selection of the optimal initial antifungal therapy.     

Invasive aspergillosis in critically ill patients: An autopsy study

Autopsy studies show that IA is among the most commonly missed diagnoses in critically ill patients. And, because of lack of unequivocal diagnostic criteria, a timely diagnosis remains challenging. We investigate the epidemiology of and the clinical risk factors for IA in critically ill patients. We conducted a retrospective, observational study of all consecutive ICU patients with evidence of IA in the postmortem examination. During the period of the study (25 years), 893 postmortem examinations were performed in the ICU. Twenty‐five patients (2.8%) were diagnosed with IA in autopsy. Only ten (40%) were classified as IA ante‐mortem, based on the initiation of antifungal treatment. The most common comorbid conditions were corticosteroid treatment (n = 14, 56%), chronic obstructive pulmonary disease (COPD) (n = 11, 44%), immunosuppression (n = 6, 24%) and haematological malignancy (n = 5, 20%). Twenty‐three patients (92%) had three or more risk factors for IA. Critically ill patients with pulmonary infiltrates, treated with high doses intravenous corticosteroids (even for a short period of time), particularly COPD patients who developed worsening respiratory insufficiency despite appropriate treatment were at the highest risk of IA.     

Endomyocardial and pericardial aspergillosis in critically ill patients

Invasive aspergillosis(IA) is a potentially lethal complication of Aspergillus infection affecting mainly immunocompromised hosts; however, during the last two decades its incidence was increasingly observed in critically ill immunocompetent patients. The objective of this study is to describe the clinical characteristics of histologically proven endomyocardial and pericardial invasion, in the context of IA, in critically ill patients. Eight critically ill patients with histopathological confirmation of endomyocardial/pericardial aspergillosis were evaluated. Risk factors, clinical and laboratory characteristics, treatment, histopathological characteristics and mortality were recorded. Signs and symptoms of cardiac dysfunction were not observed in any of the patients. Therapy was administered to six of them shortly after the first positive culture. The observed histopathological lesions included haemorrhagic lesions, small vessels with central thrombosis and surrounding consolidated tissue with necrosis. Voriconazole, caspofungin, lipid amphotericin B and itraconazole were the used antifungals. The mortality rate was high (87.5%). Endomyocardial and pericardial aspergillosis are devastating complications of invasive aspergillosis. Clinical suspicion is low making the diagnosis difficult, therefore histopathological examination of tissues are required. The mortality is high.     

Observational study on candidaemia at a university hospital in southern Italy from 1998 to 2004

In an observational study on candidaemia in hospitalised patients, conducted in a southern Italy hospital during 1998-2004, 155 cases were noted. Candida albicans (CA) was isolated in 71 (45.8%) cases involving mainly patients recovered in ICU, General Surgery and Neonatology. Candida non-albicans (CnA) species were isolated by 84 (54.2%) candidaemic patients, and in particular, Candida parapsilosis was the most frequent species isolated in Pediatric Oncology. 91.6% of the patients had a central venous catheter and only 46.4% were receiving antifungal prophylaxis. Among these patients, 87.5% (63) developed CnA infections; in particular, 41 patients had a C. parapsilosis bloodstream infection. During our study, we observed a variable drift from 1998 to 2003; we registered an evident increment of CnA candidaemia (76.9%) and a decrease of CA cases (23%) only in 2004. The mortality was 26.7%, and we observed that CA was associated with the highest rate of mortality (53.6%). Although Candida infections are correlated primarily with risk factors, their resolution depends on timely diagnosis and early therapy.     

Creation and assessment of a clinical predictive model for candidaemia in patients with candiduria

Candidaemia is the most common clinical presentation of invasive candidiasis and is a major cause of morbidity and mortality. Candiduria is a predictor for candidaemia; however, patient characteristics that are associated with concurrent candidaemia in the setting of candiduria are unclear. Identifying these characteristics could aid in the early detection of systemic disease. We performed a retrospective cohort analysis of hospitalised patients with candiduria at our institution over a 13‐year period. Our evaluation of patient characteristics included demographics, comorbidities, medications, procedures, devices, vital signs and laboratory values. We developed a multivariable logistic model to identify factors associated with candidaemia in patients with candiduria. We identified 4240 patients with candiduria, 263 (6.2%) of whom had candidaemia. Predictors for increased risk of candidaemia with candiduria included hospitalisations > 12 days, central venous catheter, parenteral nutrition, haematological and gynaecological malignancy, and receipt of β‐lactam/β‐lactamase inhibitors. Vital signs and laboratory values associated with candidaemia included elevated heart rate, temperature and creatinine, along with neutropenia and neutrophilia. Factors that demonstrated a decreased risk of candidaemia included diabetes mellitus, gastrostomy and urinary catheter with antibiotic use. The c‐statistic was 0.741 (95% CI, 0.710‐0.772). We identified a set of clinical characteristics that can predict the presence of candidaemia with candiduria.     

Risk factors,clinical presentation and prognosis of mixed candidaemia: a population‐based surveillance in Spain

The low incidence of mixed candidaemia (MC) may have precluded a better knowledge of its clinical presentation. The aim of the study was to analyse the risk factors, clinical presentation and prognosis of MC episodes. A comparison between MC and monomicrobial candidaemia within a prospective programme on candidaemia was performed in 29 hospitals between April 2010 and May 2011. In fifteen episodes of candidaemia corresponding to 15 patients, out of 752, two species of Candida (1.9%) were isolated. MC was more frequent in patients with HIV infection (12%, P = 0.038) and those admitted due to extensive burns (23%, P = 0.012). The Candida species most frequently identified in MC were C. albicans 12 patients (40%), C. glabrata seven patients (23.3%) and C. parapsilosis six patients (20%). Early mortality was higher (nine patients, 60%) in patients with MC than in patients with MMC (223 patients, 30.3%, P = 0.046). In conclusion, MC was was independently associated with increased mortality even after considering other prognostic factors. MC is an infrequent event that is more common in HIV infection and in patients suffering from burns, and is associated with increased mortality.     

Role of probiotics in prevention of Candida infection in critically ill children

Candidiasis accounts for 10–20% of bloodstream infections in paediatric intensive care units (PICUs) and a significant increase in morbidity, mortality, and length of hospital stay. Enteric colonisation by Candida species is one of the most important risk factor for invasive candidiasis. The local defence mechanisms may be altered in critically ill patients, thus facilitating Candida overgrowth and candidiasis. Systemic antifungals have been proven to be effective in reducing fungal colonisation and invasive fungal infections, but their use is not without harms. Early restoration or maintenance of intestinal microbial flora using probiotics could be one of the important tools for reducing Candida infection. A few studies have demonstrated that probiotics are able to prevent Candida growth and colonisation in neonates, whereas their role in preventing invasive candidiasis in such patients is still unclear. Moreover, there are no published data on role of probiotics supplementation in the prevention of candidiasis in critically ill children beyond neonatal period. There are gap in our knowledge regarding efficacy, cost effectiveness, risk‐benefit potential, optimum dose, frequency and duration of treatment of probiotics in prevention of fungal infections in critically ill children. Studies exploring and evaluating the role of probiotics in prevention of Candida infection in critically ill children are needed.     

Epidemiology of candidaemia in a tertiary care university hospital: 10‐year experience with 381 candidaemia episodes between 2001 and 2010

Defining the epidemiology of and risk factors for candidaemia is necessary to guide empirical treatment. The objectives of this study were to determine the ranking of Candida among positive blood cultures, to define the epidemiology of candidaemia and to investigate patient characteristics and their relationship with C. albicans vs. non‐albicans Candida (NAC) candidaemia. Candidaemia episodes between January 2001 and December 2010 were evaluated retrospectively. Patient characteristics were compared across Candida species. Candida ranked as the fifth most frequently isolated pathogen. Among 381 candidaemia episodes, 58.3% were due to C. albicans, followed by C. parapsilosis (15.2%), C. tropicalis (13.4%) and C. glabrata (6.8%). No statistically significant difference was observed in the distribution of C. albicans vs. NAC (P = 0.432). Patients with NAC had significantly higher rates of haematological disorders (P < 0.001) and neutropenia (P = 0.003), and were older (P = 0.024) than patients with C. albicans, whereas patients with urinary catheters had higher rates of C. albicans (P = 0.007). On species basis, C. tropicalis was more frequently isolated from patients with haematological disorders (P < 0.001) and neutropenia (P = 0.008). Patients with urinary catheters were less likely to have C. parapsilosis (P = 0.043). C. glabrata was most prevalent among patients with solid organ tumours (P = 0.038), but not evident in patients with haematological disorders. Local epidemiological features and risk factors may have important implications for the management of candidaemia.     

重症患者肠内喂养障碍的现状及其影响因素

目的 从护士角度探讨重症监护室患者肠内营养喂养障碍现状,分析其影响因素.方法 本研究为横断面调查.采用便利抽样法,选取青海省第五人民医院、西宁市第二人民医院、青海省人民医院、西宁市第一人民医院、青海省中医院2018年6月至2019年6月180例重症加强护理病房(ICU)护士为研究对象.采用问卷调查收集ICU患者肠内喂养...     

To treat or not to treat – critically ill patients with candiduria

The prevalence of candiduria has increased in patients admitted to intensive care units (ICUs) and it has emerged as a common nosocomial infection among critically ill patients. Generally, urinary candidiasis should be regarded as a risk factor for invasive candidiasis, but not as a disease that needs to be treated on its own. However, decision-making in critically ill patients with candiduria may become a balancing act, because candiduria may be the only indication for invasive candidaemia with significant morbidity and mortality. Of further concern, there is a worldwide increase in the incidence of non- albicans spp. isolated from urine with highly variable susceptibility to fluconazole, which has been the first-line therapy for Candida infections during the last decades. This article discusses everyday problems with urinary candidiasis in interdisciplinary ICUs.     

Risk factors for thyroid cancer: a prospective cohort study

Given the higher incidence rate of thyroid cancer among women compared to men and evidence that smoking and alcohol consumption may be inversely related to thyroid cancer risk, we examined thyroid cancer risk in association with menstrual, reproductive and hormonal factors, and cigarette and alcohol consumption, in a prospective cohort study of 89,835 Canadian women aged 40-59 at recruitment who were enrolled in the National Breast Screening Study (NBSS). Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models (using age as the time scale) were used to estimate hazard ratios and 95% confidence intervals for the association between each of the potential risk factors and risk of thyroid cancer overall and by the main histologic subtypes. During a mean of 15.9 years of follow-up, we observed 169 incident thyroid cancer cases. There was no evidence of altered overall thyroid cancer risk with any of the menstrual, reproductive, or hormonal factors. There was evidence of a decreased risk of papillary thyroid cancer among women with 5 or more live births (vs. nulliparous). Age at which smoking commenced, duration of smoking, number of cigarettes smoked per day, pack-years of smoking and alcohol consumption were not associated with altered thyroid cancer risk. The present study provides little support for associations with hormonal factors, smoking, or alcohol consumption, but there is a need for additional prospective data.     

Aspergillus tracheobronchitis in critically ill patients with chronic obstructive pulmonary diseases

Aspergillus tracheobronchitis (ATB) is considered as an unusual form of invasive aspergillosis and has a fatal outcome. There is little current information on several aspects of chronic obstructive pulmonary diseases (COPD) complicated by ATB, the frequency of which is expected to increase in the coming years. In a prospective study of invasive bronchial‐pulmonary aspergillosis (IBPA) in a critically ill COPD population, three proven cases of ATB were identified. The three new cases, combined with eight previously reported cases of COPD with ATB over a 30‐year period (1983–2013), were analysed. Among 153 critically ill COPD patients admitted to the ICU, eight cases were complicated by ATB [23.5% of IBPA (8 of 34); and 5.2% of COPD (8 of 153)], and three cases were finally diagnosed as proven ATB by histopathological findings. Among the three new cases reported and the eight published cases, the overall mortality rate was 72.7% (8 of 11 cases), with a median of 11.5 days (range, 7–27 days) between admission to death. The mortality rate was significantly higher in patients with invasive pulmonary aspergillosis (IPA) [100% (8 of 8 patients)] than in patients without parenchyma invasion [0% (0 of 3 patient), P = 0.006]. Seven patients (77.8%) received systemic corticosteroid therapy and three patients (33.3%) inhaled corticosteroids before diagnosis with ATB. Dyspnoea resistant to corticosteroids (77.8%) was the most frequent symptom. The radiological manifestations progressed rapidly in three patients (75%) who had normal chest X‐rays (CXRs) at admission. Pseudomembranous lesions were the most frequent form (54.5%) observed by bronchoscopy. Aspergillus fumigatus was the most frequently isolated pathogen (40%). ATB is an uncommon cause of exacerbation in approximately 5% of critically ill COPD patients admitted to the ICU, and may progress rapidly to IPA with a high mortality rate. Dyspnoea resistant to corticosteroids and appropriate antibiotics with a negative CXR should raise the suspicion of ATB. Early diagnosis of ATB is based on bronchoscopic examination and proven diagnosis maybe safely established with a bronchial mucous biopsy.     

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units

Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12‐months (2014‐2015) hospital‐ and laboratory‐based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross‐resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30‐day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.     

Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study

Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour‐related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997‐2012, except those identified as high‐risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow‐up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person‐years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30–5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80–6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.     

Improvement of a clinical prediction rule for clinical trials on prophylaxis for invasive candidiasis in the intensive care unit

We created a clinical prediction rule to identify patients at risk of invasive candidiasis (IC) in the intensive care unit (ICU) (Eur J Clin Microbiol Infect Dis 2007; 26 :271). The rule applies to <10% of patients in ICUs. We sought to create a more inclusive rule for clinical trials. Retrospective review of patients admitted to ICU ≥ 4 days, collecting risk factors and outcomes. Variations of the rule based on introduction of mechanical ventilation and risk factors were assessed. We reviewed 597 patients with a mean APACHE II score of 14.4, mean ICU stay of 12.5 days and mean ventilation time of 10.7 days. A variation of the rule requiring mechanical ventilation AND central venous catheter AND broad spectrum antibiotics on days 1–3 AND an additional risk factor applied to 18% of patients, maintaining the incidence of IC at 10%. Modification of our original rule resulted in a more inclusive rule for studies.     

危重恶性肿瘤患者术后早期肠内应用谷氨酰胺的作用

目的探讨危重恶性肿瘤患者术后早期应用谷氨酰胺的临床效果。方法选取2011年1月至2012年12月间110例危重恶性肿瘤患者为研究对象,按照随机数字法分为对照组和观察组,对照组55例患者给予常规标准营养支持治疗,观察组55例患者给予谷氨酰胺支持治疗,观察两组的应用效果。结果治疗前观察组和对照组的白蛋白(ALB)、前白蛋白(PAB)和转铁蛋白(TRF)比较,差异无统计学意义(P>0.05);治疗后,对照组和观察组的PAB和TRF比较,差异有统计学意义(P<0.05)。治疗前,对照组和观察组的免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋M(IgM)比较,差异无统计学意义(P>0.05);治疗后,对照组和观察组IgG比较,差异有统计学意义(P<0.05)。治疗前,对照组和观察组的BW、APACHEⅡ评分、C反应蛋白(CRP)比较,差异无统计学意义(P>0.05);治疗后,对照组和观察组的APACHEⅡ评分、CRP比较,差异有统计学意义(P<0.05)。观察组患者的ICU住院时间和术后感染发生率均明显低于对照组,差异有统计学意义(P<0.05)。结论对于危重恶性肿瘤患者术后早期给予谷氨酰胺,能够有效地改善患者术后的营养状况,增强患者的机体免疫力,提高临床治疗效果。     

Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006-2008)

Critically ill patients admitted to intensive care units (ICU) are highly susceptible to healthcare-associated infections caused by fungi. A prospective sequential survey of invasive fungal infections was conducted from May 2006 to April 2008 in 38 ICUs of 27 Italian hospitals. A total of 384 fungal infections (318 invasive Candida infections, three cryptococcosis and 63 mould infections) were notified. The median rate of candidaemia was 10.08 per 1000 admissions. In 15% of cases, the infection was already present at the time of admission to ICU. Seventy-seven percent of Candida infections were diagnosed in surgical patients. Candida albicans was isolated in 60% of cases, Candida glabrata and Candida parapsilosis in 13%, each. Candida glabrata had the highest crude mortality rate (60%). Aspergillus infection was diagnosed in 32 medical and 25 surgical patients. The median rate was 6.31 per 1000 admissions. Corticosteroid treatment was the major host factor. Aspergillosis was demonstrated to be more severe than candidiasis as the crude mortality rate was significantly higher (63% vs. 46%), given an equal index of severity, Simplified Acute Physiology Score (SAPS-II). The present large nationwide survey points out the considerable morbidity and mortality of invasive fungal infections in surgical as well as medical patients in ICU.