Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review

Mechanically ventilated critically ill patients frequently develop ventilator-associated pneumonia (VAP), a life-threatening complication. Proposed preventive measures against VAP include, but are not restricted to, selective decontamination of the digestive tract (SDD), selective oropharyngeal decontamination (SOD) and the use of probiotics. Probiotics are live bacteria that could have beneficial effects on the host by altering gastrointestinal flora. Similar to SDD and SOD, a prescription of probiotics aims at the prevention of secondary colonization of the upper and/or lower digestive tract. We performed a literature review to describe the differences and similarities between SDD/SOD and probiotic preventive strategies, focusing on (a) efficacy, (b) risks, and (c) the routing of these strategies. Reductions in the incidence of VAP have been achieved with SDD and SOD. Two large randomized controlled trials even showed reduced mortality with these preventive strategies. Randomized controlled trials of probiotic strategies also showed a reduction of the incidence of VAP, but trials were too small to draw firm conclusions. Preventive strategies with antibiotics and probiotics may be limited due to the risk of emerging resistance to the locally applied antibiotics and the risk of probiotic-related infections, respectively. The majority of trials of SDD and SOD did not exhaustively address the issue of emerging resistance. Likewise, trials of probiotic strategies did not adequately address the risk of colonization with probiotics and probiotic-related infection. In studies of SDD and SOD the preventive strategy aimed at decontamination of the oral cavity, throat, stomach and intestines, and the oral cavity and throat, respectively. In the vast majority of studies of probiotic therapy the preventive strategy aimed at decontamination of the stomach and intestines. Prophylactic use of antibiotics in critically ill patients is effective in reducing the incidence of VAP. Probiotic strategies deserve consideration in future well-powered trials. Future studies are needed to determine if preventive antibiotic and probiotic strategies are safe with regard to development of antibiotic resistance and probiotic infections. It should be determined whether the efficacy of probiotics improves when these agents are provided to the mouth and the intestines simultaneousl

Selective Decontamination of the Digestive Tract Reduces Pneumonia and Mortality

Selective decontamination of the digestive tract (SDD) has been subject of numerous randomized controlled trials in critically ill patients. Almost all clinical trials showed SDD to prevent pneumonia. Nevertheless, SDD has remained a controversial strategy. One reason for why clinicians remained reluctant to implement SDD into daily practice could be that mortality was reduced in only 2 trials. Another reason could be the heterogeneity of trials of SDD. Indeed, many different prophylactic antimicrobial regimes were tested, and dissimilar diagnostic criteria for pneumonia were applied amongst the trials. This heterogeneity impeded interpretation and comparison of trial results. Two other hampering factors for implementation of SDD have been concerns over the risk of antimicrobial resistance and fear for escalation of costs associated with the use of prophylactic antimicrobials. This paper describes the concept of SDD, summarizes the results of published trials of SDD in mixed medical-surgical intensive care units, and rationalizes the risk of antimicrobial resistance and rise of costs associated with this potentially life-saving preventive strategy

Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19

Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Intensive care medicine in an ageing population

The Dutch population is ageing, and this has an impact on our healthcare. Although currently less than 5% of our population is aged 80 years and older, they are responsible for more than 10% of the hospital admissions and 15% of the ICU admissions. This thesis illustrates that, despite significantly decreased mortality rates for both younger and very old patients over time, the mortality risks of the patients aged 80 years and older are still twice as high as that of younger patients. In addition, their remaining life expectancy is lower, ICU treatment often is burdensome and expensive and many patients who do survive, will suffer from functional and/or cognitive decline. The balance between potential benefits and burden of ICU treatment may therefore be more negative than in younger patients. This stresses the need to weigh the proportionality of ICU treatment carefully. Although older patients often have less to gain from an ICU admission than younger patients, ICU treatment certainly can be beneficial, even for patients over 90 years. Nearly 3 out of 4 ICU patients aged 90 years and older survived until hospital discharge and half of the patients were still alive one year after ICU-admission. Of the very old patients admitted with sepsis, about half died during hospitalization and more than two-thirds had died after one year. However, not sepsis, but frailty, age and disease severity (SOFA) were identified as predictors for mortality. The simple qSOFA showed to be a poorly sensitive predictive score for mortality. Under normal circumstances, age is, together with other risk factors, weighed as a risk factor for poor outcome. This may lead to the shared decision to forego ICU treatment, but it cannot be justified to withhold ICU admission for all patients above a certain age. However, in times of scarcity, not only the proportionality of treatment and autonomy of the patient but also the shortage of resources may play a role in ICU admission decisions. Therefore, it could be justified to prioritize the younger patients in circumstances of a pandemic, according to the utilitarian approach, which aims to maximize the benefits for the largest number of people and prioritize care based on the (estimated) greatest advantage of ICU treatment, the so-called incremental probability of survival. The use of age as a selection criterion in case of scarcity can also be justified by pointing at the "fair innings" that a patient has had, meaning that older patients have already had their opportunity to reach a certain "mature" age, which has given them a fair equality of opportunity. This strategy does not amount to age discrimination as all people are treated alike: everyone will become older, and thereby their claim on life-sustaining treatment decreases. In conclusion, decision-making in very old patients requiring ICU treatment remains complex. Physicians should carefully address the prognosis and risk factors and explore the preferences, treatment goals, expectations and personal values of the very old patients

Intensive care medicine in an ageing population

The Dutch population is ageing, and this has an impact on our healthcare. Although currently less than 5% of our population is aged 80 years and older, they are responsible for more than 10% of the hospital admissions and 15% of the ICU admissions. This thesis illustrates that, despite significantly decreased mortality rates for both younger and very old patients over time, the mortality risks of the patients aged 80 years and older are still twice as high as that of younger patients. In addition, their remaining life expectancy is lower, ICU treatment often is burdensome and expensive and many patients who do survive, will suffer from functional and/or cognitive decline. The balance between potential benefits and burden of ICU treatment may therefore be more negative than in younger patients. This stresses the need to weigh the proportionality of ICU treatment carefully. Although older patients often have less to gain from an ICU admission than younger patients, ICU treatment certainly can be beneficial, even for patients over 90 years. Nearly 3 out of 4 ICU patients aged 90 years and older survived until hospital discharge and half of the patients were still alive one year after ICU-admission. Of the very old patients admitted with sepsis, about half died during hospitalization and more than two-thirds had died after one year. However, not sepsis, but frailty, age and disease severity (SOFA) were identified as predictors for mortality. The simple qSOFA showed to be a poorly sensitive predictive score for mortality. Under normal circumstances, age is, together with other risk factors, weighed as a risk factor for poor outcome. This may lead to the shared decision to forego ICU treatment, but it cannot be justified to withhold ICU admission for all patients above a certain age. However, in times of scarcity, not only the proportionality of treatment and autonomy of the patient but also the shortage of resources may play a role in ICU admission decisions. Therefore, it could be justified to prioritize the younger patients in circumstances of a pandemic, according to the utilitarian approach, which aims to maximize the benefits for the largest number of people and prioritize care based on the (estimated) greatest advantage of ICU treatment, the so-called incremental probability of survival. The use of age as a selection criterion in case of scarcity can also be justified by pointing at the "fair innings" that a patient has had, meaning that older patients have already had their opportunity to reach a certain "mature" age, which has given them a fair equality of opportunity. This strategy does not amount to age discrimination as all people are treated alike: everyone will become older, and thereby their claim on life-sustaining treatment decreases. In conclusion, decision-making in very old patients requiring ICU treatment remains complex. Physicians should carefully address the prognosis and risk factors and explore the preferences, treatment goals, expectations and personal values of the very old patients

Selective Decontamination of the Digestive Tract Reduces Pneumonia and Mortality

Selective decontamination of the digestive tract (SDD) has been subject of numerous randomized controlled trials in critically ill patients. Almost all clinical trials showed SDD to prevent pneumonia. Nevertheless, SDD has remained a controversial strategy. One reason for why clinicians remained reluctant to implement SDD into daily practice could be that mortality was reduced in only 2 trials. Another reason could be the heterogeneity of trials of SDD. Indeed, many different prophylactic antimicrobial regimes were tested, and dissimilar diagnostic criteria for pneumonia were applied amongst the trials. This heterogeneity impeded interpretation and comparison of trial results. Two other hampering factors for implementation of SDD have been concerns over the risk of antimicrobial resistance and fear for escalation of costs associated with the use of prophylactic antimicrobials. This paper describes the concept of SDD, summarizes the results of published trials of SDD in mixed medical-surgical intensive care units, and rationalizes the risk of antimicrobial resistance and rise of costs associated with this potentially life-saving preventive strategy