Invasive candidiasis in critical care: challenges and future directions.

Invasive candidiasis is the most common critical care-associated fungal infection with a crude mortality of ~ 40-55%. Important factors contributing to risk of invasive candidiasis in ICU include use of broad-spectrum antimicrobials, immunosuppressive drugs, and total parenteral nutrition alongside iatrogenic interventions which breach natural barriers to infection [vascular catheters, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), surgery]. This review discusses three key challenges in this field. The first is the shift in Candida epidemiology across the globe to more resistant non-albicans species, in particular, the emergence of multi-resistant Candida glabrata and Candida auris, which pose significant treatment and infection control challenges in critical care. The second challenge lies in the timely and appropriate initiation and discontinuation of antifungal therapy. Early antifungal strategies (prophylaxis, empirical and pre-emptive) using tools such as the Candida colonisation index, clinical prediction rules and fungal non-culture-based tests have been developed: we review the evidence on implementation of these tools in critical care to aid clinical decision-making around the prescribing and cessation of antifungal therapy. The third challenge is selection of the most appropriate antifungal to use in critical care patients. While guidelines exist to aid choice, this heterogenous and complex patient group require a more tailored approach, particularly in cases of acute kidney injury, liver impairment and for patients supported by extracorporeal membrane oxygenation. We highlight key research priorities to overcome these challenges in the future

Influenza and associated co-infections in critically ill immunosuppressed patients

BackgroundIt is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure.MethodsPreplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality.ResultsInfluenza infection status was categorized into four groups: patients with influenza alone (n=95, 5.8%), patients with influenza plus pulmonary co-infection (n=58, 3.6%), patients with non-influenza pulmonary infection (n=820, 50.9%), and patients without pulmonary infection (n=638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (PPeer reviewe

Procalcitonin levels in candidemia versus bacteremia: A systematic review

Background: Procalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in the in the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia. Methods: PubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia. Results: We included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-D-glucan) but more data is needed. Conclusions: PCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence

Procalcitonin levels in candidemia versus bacteremia: A systematic review

open7BackgroundProcalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in thein the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia.MethodsPubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia.ResultsWe included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-d-glucan) but more data is needed.ConclusionsPCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence.openCortegiani A.; Misseri G.; Ippolito M.; Bassetti M.; Giarratano A.; Martin-Loeches I.; Einav S.Cortegiani, A.; Misseri, G.; Ippolito, M.; Bassetti, M.; Giarratano, A.; Martin-Loeches, I.; Einav, S

Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality

PURPOSE: To provide a practical overview of the management of the potential organ donor in the intensive care unit. METHODS: Seven areas of donor management were considered for this review: hemodynamic management; fluids and electrolytes; respiratory management; endocrine management; temperature management; anaemia and coagulation; infection management. For each subchapter, a narrative review was conducted. RESULTS AND CONCLUSIONS: Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations, or extrapolations from general ICU management strategies, and not on evidence from randomized controlled trials. The cardiorespiratory management of brain-dead donors is very similar to the management of critically ill patients, and the same applies to the management of anaemia and coagulation. Central diabetes insipidus is of particular concern, and should be diagnosed based on clinical criteria. Depending on the degree of vasopressor dependency, it can be treated with intermittent desmopressin or continuous vasopressin, intravenously. Temperature management of the donor is an area of uncertainty, but it appears reasonable to strive for a core temperature of > 35 °C. The indications and controversies regarding endocrine therapies, in particular thyroid hormone replacement therapy, and corticosteroid therapy, are discussed. The potential donor should be assessed clinically for infections, and screening tests for specific infections are an essential part of donor management. Although the rate of infection transmission from donor to receptor is low, certain infections are still a formal contraindication to organ donation. However, new antiviral drugs and strategies now allow organ donation from certain infected donors to be done safely

The Dynamics of the Pulmonary Microbiome During Mechanical Ventilation in the Intensive Care Unit and the Association with Occurrence of Pneumonia

RATIONALE: Ventilator-associated pneumonia (VAP) is the most common nosocomial infections in patients admitted to the ICU. The adapted island model predicts several changes in the respiratory microbiome during intubation and mechanical ventilation. OBJECTIVES: We hypothesised that mechanical ventilation and antibiotic administration decrease the diversity of the respiratory microbiome and that these changes are more profound in patients who develop VAP. METHODS: Intubated and mechanically ventilated ICU-patients were included. Tracheal aspirates were obtained three times a week. 16S rRNA gene sequencing with the Roche 454 platform was used to measure the composition of the respiratory microbiome. Associations were tested with linear mixed model analysis and principal coordinate analysis. MEASUREMENTS AND MAIN RESULTS: 111 tracheal aspirates were obtained from 35 patients; 11 had VAP, 18 did not have VAP. Six additional patients developed pneumonia within the first 48 hours after intubation. Duration of mechanical ventilation was associated with a decrease in α diversity (Shannon index; fixed-effect regression coefficient (β): -0.03 (95% CI -0.05 to -0.005)), but the administration of antibiotic therapy was not (fixed-effect β: 0.06; 95% CI -0.17 to 0.30). There was a significant difference in change of β diversity between patients who developed VAP and control patients for Bray-Curtis distances (p=0.03) and for Manhattan distances (p=0.04). Burkholderia, Bacillales and, to a lesser extent, Pseudomonadales positively correlated with the change in β diversity. CONCLUSION: Mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome. Dysbiosis of microbial communities in the respiratory tract was most profound in patients who developed VAP.info:eu-repo/semantics/publishedVersio

Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit

Global epidemiological data regarding outcomes for patients in intensive care units (ICUs) are scarce, but are important in understanding the worldwide burden of critical illness. We, therefore, did an international audit of ICU patients worldwide and assessed variations between hospitals and countries in terms of ICU mortality

Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community-acquired pneumonia

N.J.S. is partially funded by the Department of Veterans Affairs, Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative Grant (HX002263-01A1).Background and objective : Enterobacteriaceae (EB) spp. family is known to include potentially multidrug-resistant (MDR) microorganisms, and remains as an important cause of community-acquired pneumonia (CAP) associated with high mortality. The aim of this study was to determine the prevalence and specific risk factors associated with EB and MDR-EB in a cohort of hospitalized adults with CAP. Methods : We performed a multinational, point-prevalence study of adult patients hospitalized with CAP. MDR-EB was defined when ≥3 antimicrobial classes were identified as non-susceptible. Risk factors assessment was also performed for patients with EB and MDR-EB infection. Results : Of the 3193 patients enrolled with CAP, 197 (6%) had a positive culture with EB. Fifty-one percent (n = 100) of EB were resistant to at least one antibiotic and 19% (n = 38) had MDR-EB. The most commonly EB identified were Klebsiella pneumoniae (n = 111, 56%) and Escherichia coli (n = 56, 28%). The risk factors that were independently associated with EB CAP were male gender, severe CAP, underweight (body mass index (BMI) < 18.5) and prior extended-spectrum beta-lactamase (ESBL) infection. Additionally, prior ESBL infection, being underweight, cardiovascular diseases and hospitalization in the last 12 months were independently associated with MDR-EB CAP. Conclusion : This study of adults hospitalized with CAP found a prevalence of EB of 6% and MDR-EB of 1.2%, respectively. The presence of specific risk factors, such as prior ESBL infection and being underweight, should raise the clinical suspicion for EB and MDR-EB in patients hospitalized with CAP.PostprintPeer reviewe

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome

To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P =.796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS

How the Emotional Content of Discourse Affects Language Comprehension

Emotion effects on cognition have often been reported. However, only few studies investigated emotional effects on subsequent language processing, and in most cases these effects were induced by non-linguistic stimuli such as films, faces, or pictures. Here, we investigated how a paragraph of positive, negative, or neutral emotional valence affects the processing of a subsequent emotionally neutral sentence, which contained either semantic, syntactic, or no violation, respectively, by means of event-related brain potentials (ERPs). Behavioral data revealed strong effects of emotion; error rates and reaction times increased significantly in sentences preceded by a positive paragraph relative to negative and neutral ones. In ERPs, the N400 to semantic violations was not affected by emotion. In the syntactic experiment, however, clear emotion effects were observed on ERPs. The left anterior negativity (LAN) to syntactic violations, which was not visible in the neutral condition, was present in the negative and positive conditions. This is interpreted as reflecting modulatory effects of prior emotions on syntactic processing, which is discussed in the light of three alternative or complementary explanations based on emotion-induced cognitive styles, working memory, and arousal models. The present effects of emotion on the LAN are especially remarkable considering that syntactic processing has often been regarded as encapsulated and autonomous