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Abstract Purpose This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy. Methods This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia. Results Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups. Conclusions Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies. …

Abstract Purpose This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy. Methods This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia. Results Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups. Conclusions Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies. …

Abstract Purpose Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known. Methods Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values. Results In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747–0.880) and 0.784 (0.691–0.855), respectively. Conclusion SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero. …

Abstract Purpose Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known. Methods Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values. Results In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747–0.880) and 0.784 (0.691–0.855), respectively. Conclusion SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero. …

Abstract Introduction Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. Methods We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. Results Seventy-five patients were available for analyses. Median age was 60 [25th–75th percentile: 50–69] years, 27% were female, and median SOFA score was 12 [11–14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0–17.2] ng/mL compared to those without ARDS at 7.1 [3.7–10.1] (p 

Abstract Introduction In Sofala province (Mozambique), young people living with HIV (YPLHIV) are estimated at 7% among people aged 15–24 years. Even though the COVID-19 pandemic threatened HIV health services, data on the impact of COVID-19 on YPLHIV people are lacking. This study aimed at exploring the seroprevalence of SARS-CoV-2 and associated factors among young people based on their HIV status. Methods A cross-sectional study was conducted, including people aged 18–24 attending a visit at one of the adolescent-friendly health services in Sofala province between October and November 2022. People vaccinated against SARS-COV-2 or YPLHIV with WHO stage III-IV were excluded. A SARS-CoV-2 antibodies qualitative test and a questionnaire investigating socio-demographic and clinical characteristics were proposed. SARS-CoV-2 seroprevalence was calculated with Clopper-Pearson method. The odds ratio (OR) of a positive SARS-CoV-2 antibodies test was estimated through multivariable binomial logistic regression. Results In total, 540 young people including 65.8% women and 16.7% YPLHIV participated in the survey.. The mean age was 20.2 years (SD 2.0). Almost all the sample (96.1%) reported adopting at least one preventive measure for COVID-19. The weighted seroprevalence of SARS-CoV-2 in the whole sample was 46.8% (95%CI 42.6–51.2) and 35.9% (95%CI 25.3–47.5) in YPLHIV. The adjusted OR of testing positive at the SARS-CoV-2 antibodies test was higher in students compared to workers (aOR:2.02[0.95CI 1.01–4.21]) and in those with symptoms (aOR:1.52[0.95CI 1.01–2.30]). There were no differences based on HIV status(aOR:0.663[95%CI 0.406–1.069]). Overall, COVID-19 symptoms were reported by 68 (28.2%) people with a positive serological SARS-CoV-2 test and by 7 (21.7%) YPLHIV (p = 0.527). No one required hospitalization. Conclusions SARS-CoV-2 seroprevalence was 46.8% without differences in risk of infection or clinical presentation based on HIV status. This result may be influenced by the exclusion of YPLHIV with advanced disease. The higher risk among students suggests the schools’ role in spreading the virus. It’s important to continue monitoring the impact of COVID-19 on YPLHIV to better understand its effect on screening and adherence to treatment. …

Abstract Introduction Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. Methods We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. Results Seventy-five patients were available for analyses. Median age was 60 [25th–75th percentile: 50–69] years, 27% were female, and median SOFA score was 12 [11–14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0–17.2] ng/mL compared to those without ARDS at 7.1 [3.7–10.1] (p 

IMPORTANCE: Sepsis and septic shock are major healthcare problems that need early and appropriate management. OBJECTIVES: To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study. Adult ICU patients who received cefepime for Gram-negative pneumonia or bloodstream infection (BSI) and had cefepime concentrations measured were included. Daily cefepime exposure was generated and PK/PD parameters calculated for patients. Repeated-measures mixed-effect modeling was used to evaluate the impact of PK/PD on the outcomes. MAIN OUTCOMES AND MEASURES: Change in daily SOFA score and vasopressors requirement. RESULTS: A total of 394 and 207 patients were included in the SOFA and vasopressors analyses, respectively. The mean (±sd) age was 55 years (19) and weight 81 kg (29). For the change in SOFA score, daily SOFA score, mechanical ventilation, renal replacement therapy, and number of vasopressors were included. In the vasopressors analysis, daily SOFA score, day of therapy, and hydrocortisone dose were significant covariates in the final model. Achieving cefepime concentrations above the minimum inhibitory concentration (MIC) (T>MIC) for 100% of the dosing interval was associated with 0.006 µg/kg/min decrease in norepinephrine-equivalent dose. Cefepime PK/PD did not have an impact on the daily change in SOFA score. CONCLUSIONS AND RELEVANCE: Achieving 100% T>MIC was associated with negligible decrease in vasopressors requirement in ICU patients with Gram-negative pneumonia and BSI. There was no impact on the change in SOFA score.

Abstract Background Epidemiological studies have demonstrated an association between red blood cell distribution width (RDW) and the prognosis of pneumonia-associated diseases. However, prognostic value of RDW in patients with ventilator-associated pneumonia (VAP) has yet to be investigated. This study aimed to explore the association between RDW and in-hospital mortality in VAP patients and explore predictive value of RDW for VAP patients. Methods This retrospective cohort study included 1,543 VAP patients from the Medical Information Mart for Intensive Care IV database 2008-2019. The primary outcome was considered to 30-day in-hospital mortality of VAP patients in this study. Non-high RDW level group was defined as

Abstract Background Epidemiological studies have demonstrated an association between red blood cell distribution width (RDW) and the prognosis of pneumonia-associated diseases. However, prognostic value of RDW in patients with ventilator-associated pneumonia (VAP) has yet to be investigated. This study aimed to explore the association between RDW and in-hospital mortality in VAP patients and explore predictive value of RDW for VAP patients. Methods This retrospective cohort study included 1,543 VAP patients from the Medical Information Mart for Intensive Care IV database 2008-2019. The primary outcome was considered to 30-day in-hospital mortality of VAP patients in this study. Non-high RDW level group was defined as

Abstract Background To explore the association between myocardial enzymes and one-year mortality, and establish a nomogram integrating myocardial enzymes and clinical characteristics to predict one-year mortality among sepsis patients. Methods Data of 1,983 sepsis patients were extracted from Medical Information Mart for Intensive Care III database in this retrospective cohort study. All participants were randomly split into the training set for the development of model and testing set for the internal validation at the ratio of 7:3. Univariate logistic regression was used to screen variables with statistical differences which were made for stepwise regression, obtaining the predictors associated with one-year mortality of sepsis patients. Adopted multivariate logistic regression to assess the relationship between myocardial enzymes and one-year mortality of sepsis patients. A nomogram was established in predicting the one-year survival status of sepsis patients, and the performance of developed model were compared with LDH alone, sequential organ failure assessment (SOFA), simplified acute physiology score II (SAPS II) by receiver operator characteristic, calibration, and decision curves analysis. Results The result found that LDH was associated with one-year mortality of sepsis patients [odds ratio = 1.28, 95% confidence interval (CI): 1.18–1.52]. Independent predictors, including age, gender, ethnicity, potassium, calcium, albumin, hemoglobin, alkaline phosphatase, vasopressor, Elixhauser score, respiratory failure, and LDH were identified and used to establish the nomogram (LDH-model) for predicting one-year mortality for sepsis patients. The predicted performance [area under curve (AUC) = 0.773, 95%CI: 0.748–0.798] of this developed nomogram in the training and testing sets (AUC = 0.750, 95%CI: 0.711–0.789), which was superior to that of LDH alone, SOFA score, SAPS II score. Additionally, calibration curve indicated that LDH-model may have a good agreement between the predictive and actual outcomes, while decision curve analysis demonstrated clinical utility of the LDH-model. Conclusion LDH level was related to the risk of one-year mortality in sepsis patients. A prediction model based on LDH and clinical features was developed to predict one-year mortality risk of sepsis patients, surpassing the predictive ability of LDH alone as well as conventional SAPS II and SOFA scoring systems. …

Abstract Background Early evaluation of severe mycoplasma pneumoniae pneumonia (SMPP) and the prompt utilization of fiberoptic bronchoscopic manipulation can effectively alleviate complications and restrict the progression of sequelae. This study aim to establish a nomogram forecasting model for SMPP in children and explore an optimal early therapeutic bronchoalveolar lavage (TBAL) treatment strategy. Methods This retrospective study included children with mycoplasma pneumoniae pneumonia (MPP) from January 2019 to December 2021. Multivariate logistic regression analysis was used to screen independent risk factors for SMPP and establish a nomogram model. The bootstrap method was employed and a receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy and robustness of the model. Kaplan–Meier analysis was used to assess the effect of lavage and hospitalization times. Results A total of 244 cases were enrolled in the study, among whom 68 with SMPP and 176 with non-SMPP (NSMPP). A prediction model with five independent risk factors: left upper lobe computed tomography (CT) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health assessment (APACHE) II score, bronchitis score (BS), and c-reactive protein (CRP) was established based on the multivariate logistic regression analysis. The ROC curve of the prediction model showed the area under ROC curve (AUC) was 0.985 (95% confidence interval (CI) 0.972–0.997). The Hosmer–Lemeshow goodness-of-fit test results showed that the nomogram model predicted the risk of SMPP well (χ2 = 2.127, P = 0.977). The log-rank result suggested that an early BAL treatment could shorten MPP hospitalization time (P = 0.0057). Conclusion This nomogram model, based on the left upper lobe CT score, SOFA score, APACHE II score, BS, and CRP level, represents a valuable tool to predict the risk of SMPP in children and optimize the timing of TBAL. …

This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value. Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation.

This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value. Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation.

Abstract Purpose Sepsis in critically ill patients with injury bears a high morbidity and mortality. Extensive phenotypic monitoring of leucocyte subsets in critically ill patients at ICU admission and during sepsis development is still scarce. The main objective of this study was to identify early changes in leukocyte phenotype which would correlate with later development of sepsis. Methods Patients who were admitted in a tertiary ICU for organ support after severe injury (elective cardiac surgery, trauma, necessity of prolonged ventilation or stroke) were sampled on admission (T1) and 48–72 h later (T2) for phenotyping of leukocyte subsets by flow cytometry and cytokines measurements. Those who developed secondary sepsis or septic shock were sampled again on the day of sepsis diagnosis (Tx). Results Ninety-nine patients were included in the final analysis. Nineteen (19.2%) patients developed secondary sepsis or septic shock. They presented significantly higher absolute monocyte counts and CRP at T1 compared to non-septic patients (1030/µl versus 550/µl, p = 0.013 and 5.1 mg/ml versus 2.5 mg/ml, p = 0.046, respectively). They also presented elevated levels of monocytes with low expression of L-selectin (CD62Lneg monocytes) (OR[95%CI] 4.5 (1.4–14.5), p = 0.01) and higher SOFA score (p  8) were independently associated with nosocomial sepsis occurrence. No other leucocyte count or surface marker nor any cytokine measurement correlated with sepsis occurrence. Conclusion Monocyte counts and change of phenotype are associated with secondary sepsis occurrence in critically ill patients with injury. …

Abstract Background Gram-negative bloodstream infections (GN-BSIs) are a significant clinical challenge. The utility of follow-up blood cultures (FUBCs) in GN-BSIs and their impact on mortality and antibiotic consumption are areas of debate. This study aimed to evaluate the effect of FUBCs on mortality and antibiotic consumption in patients with GN-BSIs. Methods This single-center, retrospective study was conducted in aged > 18 years of patients with GN-BSIs. FUBC was defined as a blood culture performed 2–7 days after the first blood culture. Patients were grouped as FUBC and no FUBC and compared. A 1:1 match analysis was performed between the groups according to the SOFA score. The matched subgroup was compared for mortality risk factors with logistic regression models. The two groups were compared for the duration of effective antibiotic therapy and total antibiotic consumption (days of therapy per 1000 patient days (DOT/1000 PD)). Results FUBC was performed in 564 (69.4%) of 812 patients. Persistent, positive and negative FUBC rates were 7.9%, 14%, and 78%, respectively. The frequency of persistent GN-BSI in patients with appropriate antibiotic therapy was 3.9%. SOFA score (OR:1.33; 95% CI, 1.23–1.44), Charlson comorbidity index score (OR:1.18; 95% CI, 1.08–1.28), hospital-acquired infections (OR:1.93; 95% CI, 1.08–3.46) and carbapenem-resistant GN-BSI (OR: 2.92; 95% CI, 1.72–4.96) were independent risk factors for mortality. No relationship was found between FUBC and mortality (p > 0.05). Duration of effective antibiotic therapy (10(4–16) vs. 15(9–20), p 

Abstract Background Gram-negative bloodstream infections (GN-BSIs) are a significant clinical challenge. The utility of follow-up blood cultures (FUBCs) in GN-BSIs and their impact on mortality and antibiotic consumption are areas of debate. This study aimed to evaluate the effect of FUBCs on mortality and antibiotic consumption in patients with GN-BSIs. Methods This single-center, retrospective study was conducted in aged > 18 years of patients with GN-BSIs. FUBC was defined as a blood culture performed 2–7 days after the first blood culture. Patients were grouped as FUBC and no FUBC and compared. A 1:1 match analysis was performed between the groups according to the SOFA score. The matched subgroup was compared for mortality risk factors with logistic regression models. The two groups were compared for the duration of effective antibiotic therapy and total antibiotic consumption (days of therapy per 1000 patient days (DOT/1000 PD)). Results FUBC was performed in 564 (69.4%) of 812 patients. Persistent, positive and negative FUBC rates were 7.9%, 14%, and 78%, respectively. The frequency of persistent GN-BSI in patients with appropriate antibiotic therapy was 3.9%. SOFA score (OR:1.33; 95% CI, 1.23–1.44), Charlson comorbidity index score (OR:1.18; 95% CI, 1.08–1.28), hospital-acquired infections (OR:1.93; 95% CI, 1.08–3.46) and carbapenem-resistant GN-BSI (OR: 2.92; 95% CI, 1.72–4.96) were independent risk factors for mortality. No relationship was found between FUBC and mortality (p > 0.05). Duration of effective antibiotic therapy (10(4–16) vs. 15(9–20), p 

OBJECTIVES: Clinical sepsis phenotypes may be defined by a wide range of characteristics such as site of infection, organ dysfunction patterns, laboratory values, and demographics. There is a paucity of literature regarding the impact of site of infection on the timing and pattern of clinical sepsis markers. This study hypothesizes that important phenotypic variation in clinical markers and outcomes of sepsis exists when stratified by infection site. DESIGN: Retrospective cohort study. SETTING: Five hospitals within the Wake Forest Health System from June 2019 to December 2019. PATIENTS: Six thousand seven hundred fifty-three hospitalized adults with a discharge International Classification of Diseases, 10th Revision code for acute infection who met systemic inflammatory response syndrome (SIRS), quick Sepsis-related Organ Failure Assessment (qSOFA), or Sequential Organ Failure Assessment (SOFA) criteria during the index hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome of interest was a composite of 30-day mortality or shock. Infection site was determined by a two-reviewer process. Significant demographic, vital sign, and laboratory result differences were seen across all infection sites. For the composite outcome of shock or 30-day mortality, unknown or unspecified infections had the highest proportion (21.34%) and CNS infections had the lowest proportion (8.11%). Respiratory, vascular, and unknown or unspecified infection sites showed a significantly increased adjusted and unadjusted odds of the composite outcome as compared with the other infection sites except CNS. Hospital time prior to SIRS positivity was shortest in unknown or unspecified infections at a median of 0.88 hours (interquartile range [IQR], 0.22–5.05 hr), and hospital time prior to qSOFA and SOFA positivity was shortest in respiratory infections at a median of 54.83 hours (IQR, 9.55–104.67 hr) and 1.88 hours (IQR, 0.47–17.40 hr), respectively. CONCLUSIONS: Phenotypic variation in illness severity and mortality exists when stratified by infection site. There is a significantly higher adjusted and unadjusted odds of the composite outcome of 30-day mortality or shock in respiratory, vascular, and unknown or unspecified infections as compared with other sites.

AbstractBackgroundSepsis surveillance using electronic health record (EHR)-based data may provide more accurate epidemiologic estimates than administrative data, but experience with this approach to estimate population-level sepsis burden is lacking.MethodsThis was a retrospective cohort study including all adults admitted to publicly-funded hospitals in Hong Kong between 2009-2018. Sepsis was defined as clinical evidence of presumed infection (clinical cultures and treatment with antibiotics) and concurrent acute organ dysfunction (≥2 point increase in baseline SOFA score). Trends in incidence, mortality, and case fatality risk (CFR) were modelled by exponential regression. Performance of the EHR-based definition was compared with 4 administrative definitions using 500 medical record reviews.ResultsAmong 13,550,168 hospital episodes during the study period, 485,057 (3.6%) had sepsis by EHR-based criteria with 21.5% CFR. In 2018, age- and sex-adjusted standardized sepsis incidence was 759 per 100,000 (relative +2.9%/year [95%CI 2.0, 3.8%] between 2009-2018) and standardized sepsis mortality was 156 per 100,000 (relative +1.9%/year [95%CI 0.9,2.9%]). Despite decreasing CFR (relative -0.5%/year [95%CI -1.0, -0.1%]), sepsis accounted for an increasing proportion of all deaths (relative +3.9%/year [95%CI 2.9, 4.9%]). Medical record reviews demonstrated that the EHR-based definition more accurately identified sepsis than administrative definitions (AUC 0.91 vs 0.52–0.55, p < 0.001).ConclusionsAn objective EHR-based surveillance definition demonstrated an increase in population-level standardized sepsis incidence and mortality in Hong Kong between 2009-2018 and was much more accurate than administrative definitions. These findings demonstrate the feasibility and advantages of an EHR-based approach for widescale sepsis surveillance.

Abstract Background Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality. Objective To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection. Methods We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described. Results We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control. Conclusion Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes. …

Abstract Background Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality. Objective To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection. Methods We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described. Results We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control. Conclusion Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes. …

IntroductionSepsis is a life-threatening immune disorder resulting from an dysregulated host response to infection. Adjuvant therapy is a valuable complement to sepsis treatment. Lipoic acid has shown potential in attenuating sepsis-induced immune dysfunction and organ injury in vivo and in vitro studies. However, clinical evidence of lipoic acid injection in sepsis treatment is lacking. Hence, we devised a randomised controlled trial to evaluate the efficacy and safety of lipoic acid injection in improving the prognosis of sepsis or septic shock patients. Methods and analysisA total of 352 sepsis patients are planned to be recruited from intensive care units (ICUs) at eight tertiary hospitals in China for this trial. Eligible participants will undergo randomisation in a 1:1 ratio, allocating them to either the control group or the experimental group. Both groups received routine care, with the experimental group also receiving lipoic acid injection and the control group receiving placebo. The primary efficacy endpoint is 28-day all-cause mortality. The secondary efficacy endpoints are as follows: ICU and hospital mortality, ICU and hospital stay, new acute kidney injury in ICU, demand and duration of life support, Sequential Organ Failure Assessment (SOFA)/Acute Physiology and Chronic Health Evaluation II (APACHE II) and changes from baseline (SOFA/Apache II), arterial blood lactate (LAC) and changes from baseline (LAC), blood procalcitonin, high-sensitivity C-reactive protein, interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumour necrosis factor-α (TNF-α) and interferon- (IFN-) and changes from baseline on day 1 (D1), D3, D5 and D7. Clinical safety will be assessed through analysis of adverse events. Ethics and disseminationThe study was approved by the Ethics Committee of Maoming People’s Hospital (approval no. PJ2020MI-019-01). Informed consent will be obtained from the participants or representatives. The findings will be disseminated through academic conferences or journal publications. Trial registrationChiCTR2000039023. …

Abstract Background P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). Methods We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. Results Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65–79 years (n = 894) and 25% among patients 

Abstract Background Previous studies found minimal evidence and raised controversy about the link between hemoglobin and 28-day mortality in sepsis patients. As a result, the purpose of this study was to examine the association between hemoglobin and 28-day death in sepsis patients by analyzing the Medical Intensive Care IV (MIMIC-IV) database from 2008 to 2019 at an advanced medical center in Boston, Massachusetts. Methods We extracted 34,916 sepsis patients from the MIMIC-IV retrospective cohort database, using hemoglobin as the exposure variable and 28-day death as the outcome variable, and after adjusting for confounders (demographic indicators, Charlson co-morbidity index, SOFA score, vital signs, medication use status (glucocorticoids, vasoactive drugs, antibiotics, and immunoglobulins, etc.)), we investigated the independent effects of hemoglobin and 28-day risk of death by binary logistic regression as well as two-piecewise linear model, respectively. Results Hemoglobin levels and 28-day mortality were shown to be non-linearly related.The inflection points were 104 g/L and 128 g/L, respectively. When HGB levels were between 41 and 104 g/L, there was a 10% decrease in the risk of 28-day mortality (OR: 0.90; 95% CI: 0.87 to 0.94, p-value = 0.0001). However, in the range of 104–128 g/L, we did not observe a significant association between hemoglobin and 28-day mortality (OR: 1.17; 95% CI: 1.00 to 1.35, P value = 0.0586). When HGB was in the range of 128–207 g/L, there was a 7% increase in the risk of 28-day mortality for every 1 unit increase in HGB (OR: 1.07; 95% CI: 1.01 to 1.15, P value = 0.0424). Conclusion In patients with sepsis, baseline hemoglobin was related to a U-shaped risk of 28-day death. When HGB was in the range of 12.8–20.7 g/dL, there was a 7% increase in the risk of 28-day mortality for every 1 unit increase in HGB. …

Objectives: To assess the association between levels of intensive care and in-hospital mortality in patients hospitalized for sepsis, stratified by Sequential Organ Failure Assessment (SOFA) score at admission. Design: A nationwide, propensity score-matched, retrospective cohort study. Setting: A Japanese national inpatient database with data on 70–75% of all ICU and high-dependency care unit (HDU) beds in Japan. Patients: Adult patients hospitalized for sepsis with SOFA scores greater than or equal to 2 on their day of admission between April 1, 2018, and March 31, 2021, were recruited. Propensity score matching was performed to compare in-hospital mortality, and patients were stratified into 10 groups according eto SOFA scores. Interventions: Two exposure and control groups according to treatment unit on day of admission: 1) ICU + HDU versus general ward and 2) ICU versus HDU. Measurements and Main Results: Of 97,070 patients, 19,770 (20.4%), 23,066 (23.8%), and 54,234 (55.9%) were treated in ICU, HDU, and general ward, respectively. After propensity score matching, the ICU + HDU group had significantly lower in-hospital mortality than the general ward group, among cohorts with SOFA scores greater than or equal to 6. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 3–5. The ICU + HDU group had significantly higher in-hospital mortality than the general ward among cohorts with SOFA scores of 2. The ICU group had lower in-hospital mortality than the HDU group among cohorts with SOFA scores greater than or equal to 12. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 5–11. The ICU group had significantly higher in-hospital mortality than the general ward group among cohorts with SOFA scores less than or equal to 4. Conclusions: Patients hospitalized for sepsis with SOFA scores greater than or equal to 6 in the ICU or HDU had lower in-hospital mortality than those in the general ward, as did those with SOFA scores greater than or equal to 12 in the ICU versus HDU.

Abstract Objective This study aimed to develop and validate a machine learning algorithm-based model for predicting invasive Klebsiella pneumoniae liver abscess syndrome(IKPLAS) in diabetes mellitus and compare the performance of different models. Methods The clinical signs and data on the admission of 213 diabetic patients with Klebsiella pneumoniae liver abscesses were collected as variables. The optimal feature variables were screened out, and then Artificial Neural Network, Support Vector Machine, Logistic Regression, Random Forest, K-Nearest Neighbor, Decision Tree, and XGBoost models were established. Finally, the model\'s prediction performance was evaluated by the ROC curve, sensitivity (recall), specificity, accuracy, precision, F1-score, Average Precision, calibration curve, and DCA curve. Results Four features of hemoglobin, platelet, D-dimer, and SOFA score were screened by the recursive elimination method, and seven prediction models were established based on these variables. The AUC (0.969), F1-Score(0.737), Sensitivity(0.875) and AP(0.890) of the SVM model were the highest among the seven models. The KNN model showed the highest specificity (1.000). Except that the XGB and DT models over-estimates the occurrence of IKPLAS risk, the other models\' calibration curves are a good fit with the actual observed results. Decision Curve Analysis showed that when the risk threshold was between 0.4 and 0.8, the net rate of intervention of the SVM model was significantly higher than that of other models. In the feature importance ranking, the SOFA score impacted the model significantly. Conclusion An effective prediction model of invasion Klebsiella pneumoniae liver abscess syndrome in diabetes mellitus could be established by a machine learning algorithm, which had potential application value. …

ObjectiveThe important effect modifiers of high disease severity on the relationship between the different volumes of early fluid resuscitation and prognosis in septic patients are unknown. Thus, this study was designed to assess whether the efficacy of different volumes in the early fluid resuscitation treatment of sepsis is affected by disease severity. DesignRetrospective cohort study. SettingAdult intensive care unit (ICU) patients with sepsis from 2001 to 2012 in the MIMIC-III database. InterventionsThe intravenous fluid volume within 6 hours after the sepsis diagnosis serves as the primary exposure. The patients were divided into the standard (≥ 30 mL/kg) and restrict (<30 mL/kg) groups. Disease severity was defined by the sequential organ failure assessment (SOFA) score at ICU admission. Propensity score matching analysis was performed to ensure the robustness of our results. Primary and secondary outcome measuresThe primary endpoint of this study was 28-day mortality. Days without needing mechanical ventilation or vasopressor administration within 28-day of ICU admission serving as the secondary endpoint. ResultsIn total, 5154 consecutive individuals were identified in data analysis, 776 patients had a primary end-point event, 386 (49.68%) in the restrict group and 387 (49.81%) in the standard group. Compared with the restrict group, the standard group had higher 28-day mortality (adjusted HR, 1.32; 95% CI 1.03 to 1.70; p=0.03) in the subgroup with a sequential organ failure assessment (SOFA) score ≥10. By contrast, the risk of mortality reduction was modest in the subgroup with an SOFA score <10 (adjusted HR, 0.85; 95% CI 0.70 to 1.03; p=0.10). The effect of the interaction between the SOFA score and fluid resuscitation strategies on the 28-day mortality was significant (p=0.0035). ConclusionsHigh disease severity modifies the relationship between the volume of fluid resuscitation and mortality in patients with sepsis in the ICU; future studies investigating this interaction are warranted. …

IntroductionSepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings. Methods and analysisThis is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ~120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with ‘moderate to severe’ chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial. Ethics and disseminationThe trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal. Trial registration numberEudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. ClinicalTrials.gov number: NCT04411472. …

ObjectivesTo compare the accuracy of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) Scores in predicting mortality among intensive care unit (ICU) patients with sepsis in a low-income and middle-income country.DesignA multicentre, cross-sectional study.SettingA total of 15 adult ICUs throughout Vietnam.ParticipantsWe included all patients aged ≥18 years who were admitted to ICUs for sepsis and who were still in ICUs from 00:00 to 23:59 of the specified study days (ie, 9 January, 3 April, 3 July and 9 October of the year 2019).Primary and secondary outcome measuresThe primary outcome was hospital all-cause mortality (hospital mortality). We also defined the secondary outcome as all-cause deaths in the ICU (ICU mortality).ResultsOf 252 patients, 40.1% died in hospitals, and 33.3% died in ICUs. SOFA Score (areas under the receiver operating characteristic curve (AUROC): 0.688 (95% CI 0.618 to 0.758); cut-off value≥7.5; PAUROC<0.001) and APACHE II Score (AUROC: 0.689 (95% CI 0.622 to 0.756); cut-off value ≥20.5; PAUROC<0.001) both had a poor discriminatory ability for predicting hospital mortality. However, the discriminatory ability for predicting ICU mortality of SOFA (AUROC: 0.713 (95% CI 0.643 to 0.783); cut-off value≥9.5; PAUROC<0.001) was fair and was better than that of APACHE II Score (AUROC: 0.672 (95% CI 0.603 to 0.742); cut-off value≥18.5; PAUROC<0.001). A SOFA Score≥8 (adjusted OR (AOR): 2.717; 95% CI 1.371 to 5.382) and an APACHE II Score≥21 (AOR: 2.668; 95% CI 1.338 to 5.321) were independently associated with an increased risk of hospital mortality. Additionally, a SOFA Score≥10 (AOR: 2.194; 95% CI 1.017 to 4.735) was an independent predictor of ICU mortality, in contrast to an APACHE II Score≥19, for which this role did not.ConclusionsIn this study, SOFA and APACHE II Scores were worthwhile in predicting mortality among ICU patients with sepsis. However, due to better discrimination for predicting ICU mortality, the SOFA Score was preferable to the APACHE II Score in predicting mortality.Clinical trials registry – India: CTRI/2019/01/016898.…

Abstract Background Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. Methods This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan–Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. Results This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06–1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. Conclusion Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. Study registration NCT04321265, registered March 19th, 2020. …

AbstractBackgroundOur aim was to analyze mortality attributable to carbapenem-resistant (CR) Gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs).MethodsProspective multicentric study including patients with GNB-BSI from19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: KPC-producing Enterobacterales, metallo-β-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aOR) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium.ResultsOverall,1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (p<0.001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB.ConclusionsIn patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

ObjectivesWe evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana.DesignProspective cohort studies.Setting and participantsFrom 2014 to 2021, participants with two or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in Cambodia and Ghana and hospitalised participants with suspected infection were enrolled in the USA. Cox proportional hazards regression was performed, and Harrell’s C-statistic calculated to determine 28-day mortality prediction performance of the quick Sequential Organ Failure Assessment (qSOFA) score ≥2, SIRS score ≥3, National Early Warning Score (NEWS) ≥5, Modified Early Warning Score (MEWS) ≥5 or Universal Vital Assessment (UVA) score ≥2. Screening tools were compared with baseline risk (age and sex) with the Wald test.ResultsThe cohorts included 567 participants (42.9% women) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia and 180 participants from Durham, North Carolina in the USA. The pooled mortality was 16.4% at 28 days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI 0.58 to 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% CI 0.64 to 0.73; p<0.001), qSOFA (C-statistic: 0.70, 95% CI 0.64 to 0.75; p<0.001), UVA score (C-statistic: 0.73, 95% CI 0.69 to 0.78; p<0.001), but not with SIRS (0.60; 95% CI 0.54 to 0.65; p=0.13). Within individual cohorts, only the UVA score in Ghana performed better than baseline risk (C-statistic: 0.77; 95% CI 0.71 to 0.83; p<0.001).ConclusionsAmong the cohorts, MEWS, NEWS, qSOFA and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.…

Abstract Introduction Sepsis has the characteristics of high incidence, high mortality of ICU patients. Early assessment of disease severity and risk stratification of death in patients with sepsis, and further targeted intervention are very important. The purpose of this study was to develop machine learning models based on sequential organ failure assessment (SOFA) components to early predict in-hospital mortality in ICU patients with sepsis and evaluate model performance. Methods Patients admitted to ICU with sepsis diagnosis were extracted from MIMIC-IV database for retrospective analysis, and were randomly divided into training set and test set in accordance with 2:1. Six variables were included in this study, all of which were from the scores of 6 organ systems in SOFA score. The machine learning model was trained in the training set and evaluated in the validation set. Six machine learning methods including linear regression analysis, least absolute shrinkage and selection operator (LASSO), Logistic regression analysis (LR), Gaussian Naive Bayes (GNB) and support vector machines (SVM) were used to construct the death risk prediction models, and the accuracy, area under the receiver operating characteristic curve (AUROC), Decision Curve Analysis (DCA) and K-fold cross-validation were used to evaluate the prediction performance of developed models. Result A total of 23,889 patients with sepsis were enrolled, of whom 3659 died in hospital. Three feature variables including renal system score, central nervous system score and cardio vascular system score were used to establish prediction models. The accuracy of the LR, GNB, SVM were 0.851, 0.844 and 0.862, respectively, which were better than linear regression analysis (0.123) and LASSO (0.130). The AUROCs of LR, GNB and SVM were 0.76, 0.76 and 0.67, respectively. K-fold cross validation showed that the average AUROCs of LR, GNB and SVM were 0.757 ± 0.005, 0.762 ± 0.006, 0.630 ± 0.013, respectively. For the probability threshold of 5–50%, LY and GNB models both showed positive net benefits. Conclusion The two machine learning-based models (LR and GNB models) based on SOFA components can be used to predict in-hospital mortality of septic patients admitted to ICU. …

Abstract Purpose Sepsis in critically ill patients with injury bears a high morbidity and mortality. Extensive phenotypic monitoring of leucocyte subsets in critically ill patients at ICU admission and during sepsis development is still scarce. The main objective of this study was to identify early changes in leukocyte phenotype which would correlate with later development of sepsis. Methods Patients who were admitted in a tertiary ICU for organ support after severe injury (elective cardiac surgery, trauma, necessity of prolonged ventilation or stroke) were sampled on admission (T1) and 48–72 h later (T2) for phenotyping of leukocyte subsets by flow cytometry and cytokines measurements. Those who developed secondary sepsis or septic shock were sampled again on the day of sepsis diagnosis (Tx). Results Ninety-nine patients were included in the final analysis. Nineteen (19.2%) patients developed secondary sepsis or septic shock. They presented significantly higher absolute monocyte counts and CRP at T1 compared to non-septic patients (1030/µl versus 550/µl, p = 0.013 and 5.1 mg/ml versus 2.5 mg/ml, p = 0.046, respectively). They also presented elevated levels of monocytes with low expression of L-selectin (CD62Lneg monocytes) (OR[95%CI] 4.5 (1.4–14.5), p = 0.01) and higher SOFA score (p < 0.0001) at T1 and low mHLA-DR at T2 (OR[95%CI] 0.003 (0.00–0.17), p = 0.049). Stepwise logistic regression analysis showed that both monocyte markers and high SOFA score (> 8) were independently associated with nosocomial sepsis occurrence. No other leucocyte count or surface marker nor any cytokine measurement correlated with sepsis occurrence. Conclusion Monocyte counts and change of phenotype are associated with secondary sepsis occurrence in critically ill patients with injury. …

Abstract Purpose Early identification of high-risk patients is an important component in improving infection prevention. The SAPS2, APACHE2, Core-10-TISS, and SOFA scores are already widely used to estimate mortality, morbidity and nursing workload, but this study evaluated their usefulness in assessing a patient’s risk of ICU-acquired infection. Methods We conducted a retrospective cohort study by analyzing all patient admissions to seven ICUs at Charité Berlin, Germany in 2017 and 2018. The four scores were documented by physicians on the day of admission. The infection control staff monitored daily whether the patients experienced lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), or primary blood stream infections (PBSIs). For each combination of scoring system and infection type, an adjusted Fine and Gray model was fitted. Results We analyzed 5053 ICU admissions and observed at least one ICU-acquired infection in N = 253 patients (incidence density: 4.73 per 1000 days). 59.0% (N = 2983) of the patients were male, median age was 66 years (IQR 55–77) and median length of stay was 6 days (IQR 4–12). All models showed that patients with a higher score value were at higher risk for ICU-acquired first PBSI, LRTI, or UTI, except for the model of APACHE2 and PBSI. Patients with a SAPS2 score of > 50 points showed an increased risk of infection of sHR = 2.34 for PBSIs (CI 1.06–5.17, p < 0.05), sHR = 2.33 for LRTIs (1.53–2.55, p < 0.001) and sHR = 2.25 for UTIs (1.23–4.13, p < 0.01) when compared to the reference group with 0–30 points. Conclusions The result of this study showed that admission scores of SAPS2, Core-10-TISS, APACHE2, and SOFA might be adequate indicators for assessing a patient’s risk of ICU-acquired infection. …