11,253 research outputs found
Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial
No full textOBJECTIVES: To determine the susceptibility profiles and the resistome of Pseudomonas aeruginosa isolates from European ICUs during a prospective cohort study (ASPIRE-ICU). METHODS: 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs of 12 antibiotics were determined by broth microdilution. Horizontally acquired β-lactamases were analysed through phenotypic and genetic assays. The first respiratory isolates from 105 patients providing such samples were analysed through WGS, including the analysis of the resistome and a previously defined genotypic resistance score. Spontaneous mutant frequencies and the genetic basis of hypermutation were assessed. RESULTS: All agents except colistin showed resistance rates above 20%, including ceftolozane/tazobactam and ceftazidime/avibactam. 24.9% of the isolates were XDR, with a wide intercountry variation (0%-62.5%). 13.2% of the isolates were classified as DTR (difficult-to-treat resistance). 21.4% of the isolates produced ESBLs (mostly PER-1) or carbapenemases (mostly NDM-1, VIM-1/2 and GES-5). WGS showed that these determinants were linked to high-risk clones (particularly ST235 and ST654). WGS revealed a wide repertoire of mutation-driven resistance mechanisms, with multiple lineage-specific mutations. The most frequently mutated genes were gyrA, parC, oprD, mexZ, nalD and parS, but only two of the isolates were hypermutable. Finally, a good accuracy of the genotypic score to predict susceptibility (91%-100%) and resistance (94%-100%) was documented. CONCLUSIONS: An overall high prevalence of resistance is documented European ICUs, but with a wide intercountry variability determined by the dissemination of XDR high-risk clones, arguing for the need to reinforce infection control measures
Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial
No full textAbstract: Objectives To determine the susceptibility profiles and the resistome of Pseudomonas aeruginosa isolates from European ICUs during a prospective cohort study (ASPIRE-ICU). Methods 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs of 12 antibiotics were determined by broth microdilution. Horizontally acquired beta-lactamases were analysed through phenotypic and genetic assays. The first respiratory isolates from 105 patients providing such samples were analysed through WGS, including the analysis of the resistome and a previously defined genotypic resistance score. Spontaneous mutant frequencies and the genetic basis of hypermutation were assessed. Results All agents except colistin showed resistance rates above 20%, including ceftolozane/tazobactam and ceftazidime/avibactam. 24.9% of the isolates were XDR, with a wide intercountry variation (0%-62.5%). 13.2% of the isolates were classified as DTR (difficult-to-treat resistance). 21.4% of the isolates produced ESBLs (mostly PER-1) or carbapenemases (mostly NDM-1, VIM-1/2 and GES-5). WGS showed that these determinants were linked to high-risk clones (particularly ST235 and ST654). WGS revealed a wide repertoire of mutation-driven resistance mechanisms, with multiple lineage-specific mutations. The most frequently mutated genes were gyrA, parC, oprD, mexZ, nalD and parS, but only two of the isolates were hypermutable. Finally, a good accuracy of the genotypic score to predict susceptibility (91%-100%) and resistance (94%-100%) was documented. Conclusions An overall high prevalence of resistance is documented European ICUs, but with a wide intercountry variability determined by the dissemination of XDR high-risk clones, arguing for the need to reinforce infection control measures
Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial
No full textObjective: To determine the susceptibility profiles and the resistome of P. aeruginosa isolates from European ICUs during a prospective cohort (ASPIRE-ICU).
Methods: 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs for 12 antibiotics were determined by broth microdilution. Horizontally-acquired β27 lactamases were analyzed through phenotypic and genetic assays. The first respiratory isolate from 105 patients providing such samples were analyzed through WGS, including the analysis of the resistome and a previously defined genotypic resistance score. Spontaneous mutant frequencies and genetic basis of hypermutation were assessed.
Results: All agents except colistin showed resistance rates above 20%, including ceftolozane/tazobactam and ceftazidime/avibactam. 24.9% of the isolates were XDR, with a wide intercountry variation (0- 62.5%). 13.2% of the isolates were classified as DTR (Difficult to Treat Resistance). 21.4% of the isolates produced ESBLs (mostly PER-1) or carbapenemases (mostly NDM-1, VIM-1/2 and GES-5). WGS showed that these determinants were linked to high-risk clones (particularly ST235 and ST654). WGS revealed a wide repertoire of mutation-driven resistance mechanisms, with multiple lineage-specific mutations. The most frequently mutated genes were gyrA, parC, oprD, mexZ, nalD and ParS, but only 2 of the isolates were hypermutable. Finally, a good accuracy of the genotypic score to predict susceptibility (91-100%) and resistance (94-100%) was documented.
Conclusions: An overall high prevalence of resistance is documented European ICUs, but with a wide intercountry variability determined by the dissemination of XDR high-risk clones, arguing for the need of reinforcement of infection control measures
Association of Staphylococcus aureus Colonization and Pneumonia in the Intensive Care Unit
No full textImportance: Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective: To quantify associations of patient-related and contextual factors, including S aureus colonization status, with the occurrence of SAIP. Design, Setting, and Participants: This cohort study was conducted in ICUs of 30 hospitals in 11 European countries, geographically spread across 4 regions. Among patients with an anticipated length of stay 48 hours or longer who were undergoing mechanical ventilation at ICU admission, S aureus colonization was ascertained in the nose and lower respiratory tract. From this group, S aureus-colonized and noncolonized patients were enrolled into the study cohort in a 1:1 ratio. Data analysis was performed from May to November 2019. Main Outcomes and Measures: SAIP was defined as any pneumonia during the ICU stay developing 48 hours or more after ICU admission with S aureus isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account. Weighted risk factor analysis was performed using Cox multivariable regression. Results: The study cohort consisted of 1933 patients (mean [SD] age, 62.0 [16.0] years); 1252 patients (64.8%) were men, and 950 patients (49.1%) were S aureus carriers at ICU admission. In all, 304 patients (15.7%) developed ICU-acquired pneumonia, of whom 131 patients (6.8%) had SAIP. Weighted SAIP incidences were 11.7 events per 1000 patient-days in the ICU for S aureus-colonized patients and 2.9 events per 1000 patient-days in the ICU for noncolonized patients (overall incidence, 4.9 events per 1000 patient-days in the ICU). The only factor independently associated with SAIP was S aureus colonization status at ICU admission (cause-specific hazard ratio, 3.6; 95% CI, 2.2-6.0; P < .001). There were marked regional differences in SAIP incidence and cause-specific hazard ratios for colonization status. Conclusions and Relevance: SAIP incidence was 4.9 events per 1000 ICU patient-days for patients undergoing mechanical ventilation at ICU admission (or shortly thereafter). The daily risk of SAIP was 3.6 times higher in patients colonized with S aureus at ICU admission compared with noncolonized patients
Impact of Pseudomonas aeruginosa carriage on intensive care unit- acquired pneumonia : a European multicentre prospective cohort study
No full textAbstract: Objectives: Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites. Methods: Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonization in the perianal area and in the lower respiratory tract was assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonization as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP. Results: A total of 1971 subjects were enrolled. The colonization prevalence with PA in the first 72 hours of ICU admission was 10.4% (179 perianal and 51 respiratory), whereas the acquisition incidence during the ICU stay was 7.0% (158 perianal and 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonized on admission and 9 (20.9%) acquired colonization before PAIP onset. Both perianal (adjusted subdistribution hazard ratio, 4.4; 95% CI, 1.7-11.6) and respiratory colonization (adjusted subdistribution hazard ratio: 4.6, 95% CI, 1.9-11.1) were independently associated with PAIP development. Discussion: PAIP incidence was higher in PA colonized vs. non-colonized patients. Colonization of both the rectum and of the respiratory tract was associated with development of PAIP. The increased risk of PA colonization for subsequent infection provides an opportunity for targeted preventive interventions. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/)
Association of staphylococcus aureus colonization and pneumonia in the intensive care unit
No full textAbstract: Importance Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective To quantify associations of patient-related and contextual factors, including S aureus colonization status, with the occurrence of SAIP. Design, Setting, and Participants This cohort study was conducted in ICUs of 30 hospitals in 11 European countries, geographically spread across 4 regions. Among patients with an anticipated length of stay 48 hours or longer who were undergoing mechanical ventilation at ICU admission, S aureus colonization was ascertained in the nose and lower respiratory tract. From this group, S aureus-colonized and noncolonized patients were enrolled into the study cohort in a 1:1 ratio. Data analysis was performed from May to November 2019. Main Outcomes and Measures SAIP was defined as any pneumonia during the ICU stay developing 48 hours or more after ICU admission with S aureus isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account. Weighted risk factor analysis was performed using Cox multivariable regression. Results The study cohort consisted of 1933 patients (mean [SD] age, 62.0 [16.0] years); 1252 patients (64.8%) were men, and 950 patients (49.1%) were S aureus carriers at ICU admission. In all, 304 patients (15.7%) developed ICU-acquired pneumonia, of whom 131 patients (6.8%) had SAIP. Weighted SAIP incidences were 11.7 events per 1000 patient-days in the ICU for S aureus-colonized patients and 2.9 events per 1000 patient-days in the ICU for noncolonized patients (overall incidence, 4.9 events per 1000 patient-days in the ICU). The only factor independently associated with SAIP was S aureus colonization status at ICU admission (cause-specific hazard ratio, 3.6; 95% CI, 2.2-6.0; P < .001). There were marked regional differences in SAIP incidence and cause-specific hazard ratios for colonization status. Conclusions and Relevance SAIP incidence was 4.9 events per 1000 ICU patient-days for patients undergoing mechanical ventilation at ICU admission (or shortly thereafter). The daily risk of SAIP was 3.6 times higher in patients colonized with S aureus at ICU admission compared with noncolonized patients. This cohort study analyzes the association of Staphylococcus aureus colonization status with the occurrence of S aureus pneumonia among European patients in the intensive care unit. Question What is the incidence density of Staphylococcus aureus intensive care unit pneumonia (SAIP) in Europe, and which factors are associated with the risk of SAIP? Findings In this cohort study of 1933 participants, the weighted incidence density of SAIP was 4.9 events per 1000 intensive care unit patient-days, and S aureus colonization was the only factor independently associated with SAIP. Meaning These findings suggest that SAIP incidence may be higher than initially perceived, and future interventions to prevent SAIP should focus on patients colonized with S aureus to achieve a higher efficacy
The blood transcriptional response in patients developing intensive care unit-acquired pneumonia
No full textAbstract: Introduction: Immune response dysregulation has been implicated in the development of intensive care unit (ICU)-acquired pneumonia. We aimed to determine differences in the longitudinal blood transcriptional response between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls). Methods: We performed a case-cohort study in mechanically ventilated trauma and surgery patients with ICU stays >2 days, enrolled in 30 hospitals across Europe. We collected blood for RNA sequencing at baseline, day 7 and (in cases) the day of pneumonia diagnosis. We performed gene set enrichment analysis and analysed longitudinal gene expression changes using linear mixed models. External validation was performed using an independent trauma cohort. Results: We enrolled 113 cases and 115 controls, with similar baseline characteristics. At baseline (median 2 days after ICU admission), cases showed upregulated gene pathways relating to innate immunity, hemostasis and metabolism, and downregulated adaptive immune pathways. These changes persisted at the day of pneumonia diagnosis (median 6 days, compared to day 7 in controls). In the longitudinal comparison, cases exhibited enhanced upregulation of innate immunity, adaptive immunity and hemostasis pathways, along with enhanced downregulation of metabolism pathways relative to controls (all P<0.00001, except hemostasis P<0.05). These findings were largely externally validated. Cases had higher quantitative sepsis response signature scores (P<0.001), reflective of immune dysregulation. Conclusion: Patients developing ICU-acquired pneumonia exhibit distinct blood transcriptional responses shortly after ICU admission and in the subsequent path to pneumonia, suggestive of broad immune dysfunction with both immunosuppressive and inflammatory features
Interdisciplinary communication in the intensive care unit
No full textBACKGROUND: Patient safety research has shown poor communication among intensive care unit (ICU) nurses and doctors to be a common causal factor underlying critical incidents in intensive care. This study examines whether ICU doctors and nurses have a shared perception of interdisciplinary communication in the UK ICU. METHODS: Cross-sectional survey of ICU nurses and doctors in four UK hospitals using a previously established measure of ICU interdisciplinary collaboration. RESULTS: A sample of 48 doctors and 136 nurses (47% response rate) from four ICUs responded to the survey. Nurses and doctors were found to have differing perceptions of interdisciplinary communication, with nurses reporting lower levels of communication openness between nurses and doctors. Compared with senior doctors, trainee doctors also reported lower levels of communication openness between doctors. A regression path analysis revealed that communication openness among ICU team members predicted the degree to which individuals reported understanding their patient care goals (adjR2 = 0.17). It also showed that perceptions of the quality of unit leadership predicted open communication. CONCLUSIONS: Members of ICU teams have divergent perceptions of their communication with one another. Communication openness among team members is also associated with the degree to which they understand patient care goals. It is necessary to create an atmosphere where team members feel they can communicate openly without fear of reprisal or embarrassment.This work was supported by a PhD studentship from the College of Life Sciences and Medicines, University of Aberdeen.Peer reviewedAuthor versio
Plasma protein biomarkers reflective of the host response in patients developing Intensive Care Unit-acquired pneumonia
No full textAbstract: Background Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls). Methods We performed a nested case\u2013control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 h enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and\u2014in cases\u2014on the day of pneumonia diagnosis. Results Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n\u2009=\u2009632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrollment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly (\u200910 days, n\u2009=\u200968) after ICU admission. Conclusions Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses
Plasma protein biomarkers reflective of the host response in patients developing Intensive Care Unit-acquired pneumonia
No full textBackground: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls). Methods: We performed a nested case–control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 h enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and—in cases—on the day of pneumonia diagnosis. Results: Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n = 632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrollment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly ( 10 days, n = 68) after ICU admission. Conclusions: Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses. Trial registration: ClinicalTrials.gov Identifier: NCT02413242, posted April 9th, 2015. Graphical abstract: [Figure not available: see fulltext.
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