We report on intensive care nosocomial pneumonia (NP) in Europe through a review of EU-VAP/CAP manuscripts: a prospective observational study, enrolling patients from 27 ICUs in nine European ...countries. From 2,436 eligible ICU patients, 827 cases presented NP, with 18.3 episodes of VAP per 1000 ventilator-days. Most common findings were worsening oxygenation, purulent respiratory secretions and temperature increase. At least three criteria from Clinical Pulmonary Infection score (CPIS) were present in 77.9 % of episodes, but only 0.2 % met six CPIS criteria. Diagnosis was confirmed mainly noninvasively (74.8 %), with half qualitative and quantitative cultures. The dominant isolate was
S. aureus
in Spain, France, Belgium and Ireland,
P. aeruginosa
in Italy and Portugal,
Acinetobacter
in Greece and Turkey, but
Escherichia coli
in Germany. NP resulted in 6 % higher mortality, longer ICU stay and duration of mechanical ventilation (12 and 10 days). COPD and age ≥45 years were not associated with higher VAP incidence but did correlate with increased mortality. Trauma had higher VAP incidence but lower mortality. Bacteremia (led by MRSA and
Acinetobacter baumannii)
was documented in 14.6 %, being associated with extra ICU stay and mortality. Vasopressors and ICUs with above 25 % prevalence of Potential Resistant Organisms (PRM) were independently associated with PRM, being documented in 50.7 % of patients with early-onset VAP without known risk factors. Most patients initially received combination therapy. Delay in appropriate antimicrobial choice significantly increased mortality, and LOS in survivors was six days longer (
p
< 0.05). In conclusion, NP management in Europe presents local differences and major shifts when compared to reports from North America, outcomes of randomized trials and general guidelines.
Cutaneous manifestations in COVID‐19: the experiences of Barcelona and Rome Tammaro, A.; Adebanjo, G.A.R.; Parisella, F.R. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
July 2020, 2020-Jul, 2020-07-00, 20200701, Letnik:
34, Številka:
7
Journal Article
The incidence of sepsis is increasing, and the condition is now the leading cause of death in general intensive care units. Our review failed to identify studies of the causes of cardiac arrest among ...infected patients, even though non-cardiac causes represent 15% of out-of-hospital cardiac arrests and though one-third of events have positive blood cultures. Sudden cardiac arrest is the result of local damage to the heart and of the impact of systemic and pulmonary conditions on cardiac performance, and its danger is underestimated. Necropsy findings in sudden death often identify myocarditis as an unexpected cause. The role of hypoxaemia, severe pulmonary thromboembolism with subsequent pulseless cardiac activity, alterations of electrolytes and hydrogen concentrations, distort fluid distribution with reduced pre-load, direct myocyte damage and adverse cardiac effects related to antibiotic use need to be defined. Many cardiac arrests might be preventable. Because cardiopulmonary resuscitation is challenging and usually unsuccessful in patients with sepsis, research is needed to help predict which patients are at risk. Only half of pneumonia patients with cardiac arrest in the ward receive prior ECG monitoring. Telemedicine and non-invasive monitoring in the ward, avoidance of antibiotics associated with prolonged QT syndrome, and adequate haemodynamic resuscitation might be important in preventing in-hospital arrests among patients with infections.
Candida
spp. are commonly found in humans, colonizing most healthy individuals. A high prevalence of invasive candidiasis has been reported in recent years. Here, we assess the relation between
...Candida
spp. as part of the human mycobiome, the host defense mechanisms, and the pathophysiology of invasive disease in critically ill patients. Many hypotheses have been proposed to explain the different immune responses to the process where
Candida
goes through healthy mycobiome to colonization to invasion; the involvement of other microbiota inhabitants, changes in temperature, low nitrogen levels, and the caspase system activation have been described. Patients admitted to an intensive care unit (ICU) are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and
Candida
colonization. The first approach should be using predictive scores as screening, followed by the determination of biomarkers (when available), and, in the near future, probably immune-genomics and analysis of the clinical background in order to initiate prompt and correct treatment. Regarding treatment, the initiation with an echinocandin is strongly recommended in critically ill patients. In conclusion, prompt treatment and adequate source control in the more severe patients remains the ultimate goal, as well as restoration of a healthy microbiota.
Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the ...heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored.
To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research.
A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed.
The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1).
A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways.
With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated ...adult patients. Although there is limited evidence describing their efficacy and safety, in an era when there is a need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher-quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to multidrug-resistant pathogens.
Purpose
Risk factors for β-lactam antibiotic underdosing in critically ill patients have not been described in large-scale studies. The objective of this study was to describe ...pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment envisioning empirical dosing in critically ill patients and considering a worst-case scenario as well as to identify patient characteristics that are associated with target non-attainment.
Methods
This analysis uses data from the DALI study, a prospective, multi-centre pharmacokinetic point-prevalence study. For this analysis, we assumed that these were the concentrations that would be reached during empirical dosing, and calculated target attainment using a hypothetical target minimum inhibitory concentration (MIC), namely the susceptibility breakpoint of the least susceptible organism for which that antibiotic is commonly used. PK/PD targets were free drug concentration maintained above the MIC of the suspected pathogen for at least 50 % and 100 % of the dosing interval respectively (50 % and 100 %
f
T
>MIC
). Multivariable analysis was performed to identify factors associated with inadequate antibiotic exposure.
Results
A total of 343 critically ill patients receiving eight different β-lactam antibiotics were included. The median (interquartile range) age was 60 (47–73) years, APACHE II score was 18 (13–24). In the hypothetical situation of empirical dosing, antibiotic concentrations remained below the MIC during 50 % and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %) patients respectively. The use of intermittent infusion was significantly associated with increased risk of non-attainment for both targets; creatinine clearance was independently associated with not reaching the 100 %
f
T
>MIC
target.
Conclusions
This study found that—in empirical dosing and considering a worst-case scenario—19 % and 41 % of the patients would not achieve antibiotic concentrations above the MIC during 50 % and 100 % of the dosing interval. The use of intermittent infusion (compared to extended and continuous infusion) was the main determinant of non-attainment for both targets; increasing creatinine clearance was also associated with not attaining concentrations above the MIC for the whole dosing interval. In the light of this study from 68 ICUs across ten countries, we believe current empiric dosing recommendations for ICU patients are inadequate to effectively cover a broad range of susceptible organisms and need to be reconsidered.
Nebulized antibiotics have an established role in patients with cystic fibrosis or bronchiectasis. Their potential benefit to treat respiratory infections in mechanically ventilated patients is ...receiving increasing interest. In this consensus statement of the European Society of Clinical Microbiology and Infectious Diseases, the body of evidence of the therapeutic utility of aerosolized antibiotics in mechanically ventilated patients was reviewed and resulted in the following recommendations: Vibrating-mesh nebulizers should be preferred to jet or ultrasonic nebulizers. To decrease turbulence and limit circuit and tracheobronchial deposition, we recommend: (a) the use of specifically designed respiratory circuits avoiding sharp angles and characterized by smooth inner surfaces, (b) the use of specific ventilator settings during nebulization including use of a volume controlled mode using constant inspiratory flow, tidal volume 8 mL/kg, respiratory frequency 12 to 15 bpm, inspiratory:expiratory ratio 50%, inspiratory pause 20% and positive end-expiratory pressure 5 to 10 cm H2O and (c) the administration of a short-acting sedative agent if coordination between the patient and the ventilator is not obtained, to avoid patient's flow triggering and episodes of peak decelerating inspiratory flow. A filter should be inserted on the expiratory limb to protect the ventilator flow device and changed between each nebulization to avoid expiratory flow obstruction. A heat and moisture exchanger and/or conventional heated humidifier should be stopped during the nebulization period to avoid a massive loss of aerosolized particles through trapping and condensation. If these technical requirements are not followed, there is a high risk of treatment failure and adverse events in mechanically ventilated patients receiving nebulized antibiotics for pneumonia.
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