Abstract Background Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies. Methods This is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients’ medical charts and electronic medical record system. Results In total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52–251). Seven patients recovered from PcP after proper management while one died of septic shock. Conclusion PcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population. …

Abstract Purposes Since 2016, the World Health Organization has recommended universal antiretroviral therapy (ART) for all people living with Human Immunodeficiency Virus (PLHIV). This recommendation may have influenced the characteristics and outcomes of PLHIV admitted to the Intensive Care Unit (ICU). This study aims to identify changes in the epidemiological and clinical characteristics of PLHIV admitted to the ICU, and their short- and medium-term outcomes before and after the implementation of universal ART (periods 2006–2015 and 2016–2019). Methods This retrospective, observational, single-center study included all adult PLHIV admitted to the ICU of a University Hospital in Barcelona from 2006 to 2019. Results The study included 502 admissions involving 428 patients, predominantly men (75%) with a median (P25-P75) age of 47.5 years (39.7–53.9). Ninety-one percent were diagnosed with HIV before admission, with 82% under ART and 60% admitted from the emergency department. In 2016–2019, there were more patients on ART pre-admission, reduced needs for invasive mechanical ventilation (IMV) and fewer in-ICU complications. ICU mortality was also lower (14% vs 7%). Predictors of in-ICU mortality included acquired immunodeficiency syndrome defining event (ADE)-related admissions, ICU complications, higher SOFA scores, IMV and renal replacement therapy (RRT) requirement. ART use during ICU admission was protective. Higher SOFA scores, admission from hospital wards, and more comorbidities predicted one-year mortality. Conclusions The in-ICU mortality of critically ill PLHIV has decreased in recent years, likely due to changes in patient characteristics. Pre- and ICU admission features remain the primary predictors of short- and medium-term outcomes. …

Abstract Background The impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients. Methods In this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase–to–Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations. Results The cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03–12.69; APRI: OR 2.16, 95% CI 0.88–5.30; NFS: OR 6.80, 95% CI 2.11–21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups. Conclusion Our study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings. …

OBJECTIVES: We aimed to summarize the most significant and impactful publications describing the pharmacotherapeutic care of critically ill patients in 2023. DATA SOURCES: PubMed/MEDLINE and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials and prospective studies of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2023, and December 31, 2023, were eligible for inclusion in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included. An a priori defined three-round modified Delphi process was employed to achieve consensus on the most impactful publications based on the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update returned a total of 1202 articles, of which 1164 were excluded. The remaining 38 articles underwent a three-round modified Delphi process. In each round, articles were independently scored based on overall contribution to scientific knowledge and novelty to the literature. Included articles are summarized and their impact discussed. Article topics included hydrocortisone for severe community-acquired pneumonia, inhaled amikacin for prevention of ventilator-associated pneumonia, methylene blue for septic shock, restrictive vs. liberal fluid management for sepsis-induced hypotension, andexanet alfa for major bleeding associated with factor Xa inhibitors, and early administration of four-factor prothrombin complex concentrate in patients with trauma at risk for massive transfusion. CONCLUSIONS: This review provides a summary and perspective on the potential impact of the most relevant articles in 2023 describing advances in the pharmacotherapeutic care of critically ill patients.

Abstract Gas gangrene is a rare presentation of a necrotizing fasciitis, caused by Clostridium perfringens, C. septicum and other clostridial species. With its rapid progression it is a potentially life-threatening infection, that poses as a challenge in the clinical management requiring an interdisciplinary approach. Here we present a 62-year-old woman, who developed neutropenic fever while undergoing chemotherapy for triple negative breast cancer. She presented with a high fever, reporting little pain in her left thigh accompanied by redness and induration locally. Subsequently the patient developed pain and redness of the back of the left hand. The initial findings suggested cellulitis and immediate empiric treatment with intravenous meropenem was started. Despite the antibiotic treatment the patient rapidly developed septic shock along with progression of the local infection. Emergency surgical debridement revealed extensive necrosis of the soft tissues including extensive myonecrosis of the thigh. On the left hand an extensive debridement was performed, the left lower limb could not be preserved and exarticulation of the left hip was required. Microbiologically C. septicum was isolated in different samples, confirming gas gangrene. As there was no local entry portal on the skin, hematogenous seeding from intestinal translocation in this neutropenic patient was suspected. The empiric antibiotic treatment was tailored to intravenous penicillin and complemented with clindamycin for toxin inhibition. Following radical debridement and antibiotic treatment, the patient could be stabilized. After repetitive debridement wound closure was achieved and the patient was discharged for rehabilitation. Antibiotic treatment was continued for four weeks. This rare case of gas gangrene in a neutropenic patient shows the complexity in the diagnostic and therapeutic management of necrotizing soft tissue infections in immunocompromised patients. It particularly highlights the importance of an interdisciplinary management with fast recognition of the disease and rapid, if needed radical, surgical debridement as well as tailored antibiotic treatment for a successful outcome. …

Abstract Cefiderocol is a new siderophore-beta-lactam antibiotic used for the treatment of severe multidrug-resistant infections like sepsis, hospital-acquired and ventilator-associated pneumonia in adults, but there are only single reports on its use in the neonatal population. We describe the successful cefiderocol treatment of a newborn with pneumogenic sepsis due to Stenotrophomonas maltophilia. …

Abstract Gas gangrene is a rare presentation of a necrotizing fasciitis, caused by Clostridium perfringens, C. septicum and other clostridial species. With its rapid progression it is a potentially life-threatening infection, that poses as a challenge in the clinical management requiring an interdisciplinary approach. Here we present a 62-year-old woman, who developed neutropenic fever while undergoing chemotherapy for triple negative breast cancer. She presented with a high fever, reporting little pain in her left thigh accompanied by redness and induration locally. Subsequently the patient developed pain and redness of the back of the left hand. The initial findings suggested cellulitis and immediate empiric treatment with intravenous meropenem was started. Despite the antibiotic treatment the patient rapidly developed septic shock along with progression of the local infection. Emergency surgical debridement revealed extensive necrosis of the soft tissues including extensive myonecrosis of the thigh. On the left hand an extensive debridement was performed, the left lower limb could not be preserved and exarticulation of the left hip was required. Microbiologically C. septicum was isolated in different samples, confirming gas gangrene. As there was no local entry portal on the skin, hematogenous seeding from intestinal translocation in this neutropenic patient was suspected. The empiric antibiotic treatment was tailored to intravenous penicillin and complemented with clindamycin for toxin inhibition. Following radical debridement and antibiotic treatment, the patient could be stabilized. After repetitive debridement wound closure was achieved and the patient was discharged for rehabilitation. Antibiotic treatment was continued for four weeks. This rare case of gas gangrene in a neutropenic patient shows the complexity in the diagnostic and therapeutic management of necrotizing soft tissue infections in immunocompromised patients. It particularly highlights the importance of an interdisciplinary management with fast recognition of the disease and rapid, if needed radical, surgical debridement as well as tailored antibiotic treatment for a successful outcome. …

Abstract Cefiderocol is a new siderophore-beta-lactam antibiotic used for the treatment of severe multidrug-resistant infections like sepsis, hospital-acquired and ventilator-associated pneumonia in adults, but there are only single reports on its use in the neonatal population. We describe the successful cefiderocol treatment of a newborn with pneumogenic sepsis due to Stenotrophomonas maltophilia. …

Abstract Background & objective The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15–20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (

Abstract Background Haemophilus influenzae causes life-threatening invasive diseases such as septicaemia and meningitis. Reports on circulating H. influenzae causing invasive disease in lower-middle income settings, including Indonesia, are lacking. This study describes the serotype distributions and whole-genome sequence (WGS) data of H. influenzae isolated from hospitalized patients at Soetomo Hospital, Surabaya, Indonesia. Methods H. influenzae isolates were isolated from blood and pleural fluid specimens and identified using culture-based and molecular methods, followed by serotyping and WGS using RT‒PCR and Illumina MiSeq, respectively. Sequencing reads were assembled, and further analyses were undertaken to determine the genomic content and reconstruct the phylogeny. A second dataset consisting of publicly available H. influenzae genomes was curated to conduct phylogenetic analyses of isolates in this study in the context of globally circulating isolates. Results Ten H. influenzae isolates from hospitalized patients were collected, and septicaemia was the most common diagnosis (n=8). RT‒PCR and WGS were performed to determine whether all the isolates were nontypeable H. influenzae (NTHi). There were four newly identified STs distributed across the two main clusters. A total of 91 out of 126 virulence factor (VF)-related genes in Haemophilus sp. were detected in at least one isolate. Further evaluation incorporating a global collection of H. influenzae genomes confirmed the diverse population structure of NTHi in this study. Conclusion This study showed that all H. influenzae recovered from invasive disease patients were nonvaccine-preventable NTHi isolates. The inclusion of WGS revealed four novel STs and the possession of key VF-associated genes. …

Abstract Background The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. Methods In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. Results A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02–1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00–1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. Conclusion Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients. …

Abstract Background Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. Methods This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. Results A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P 

Abstract Background The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. Methods In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. Results A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02–1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00–1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. Conclusion Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients. …

Abstract Background Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. Methods This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. Results A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P 

IMPORTANCE: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. OBJECTIVES: We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included. MAIN OUTCOMES AND MEASURES: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. RESULTS: Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%). CONCLUSIONS AND RELEVANCE: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.

by Chu-Yun Liu, Yu-Shen Yang, Meng-Qin Pei, He-fan He The objective of this study was to explore the potential causalities of fat mass, nonfat mass and height (henceforth, ‘anthropometric measures’) with sepsis risk and mortality. We conducted the Mendelian randomization (MR) investigation using genome-wide association study (GWAS) summary statistics of anthropometric measures, sepsis, and sepsis mortality. The GWAS summary data from the UK Biobank was used. Firstly, MR analysis was performed to estimate the causal effect of anthropometric measures on the risk of sepsis. The inverse-variance weighted (IVW) method was utilized as the primary analytical approach, together with weighted median-based method. Cochrane’s Q test and MR-Egger intercept test were performed to assess heterogeneity and pleiotropy, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. The IVW method showed that genetically predicted weight-related measures were suggestively linked to an increased risk of sepsis. However, height displayed no causal association with sepsis risk and mortality. Furthermore, weight-related measures also displayed significant MR association with the sepsis mortality, except body nonfat mass and right leg nonfat mass. However, MVMR analysis indicated the observed effects for weight-related measures in the univariable MR analyses are more likely a bias caused by the interrelationship between anthropometric measures. According to the MR-Egger intercept assessment, our MR examination was not influenced by horizontal pleiotropy (all p>0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. In conclusion, these findings provided vital new knowledge on the role of anthropometric-related measures in the sepsis etiology.

by Per Venge, Christer Peterson, Shengyuan Xu, Anders Larsson, Joakim Johansson, Jonas Tydén Introduction Sepsis is a growing problem worldwide and associated with high mortality and morbidity. The early and accurate diagnosis and effective supportive therapy are critical for combating mortality. The aim of the study was to compare the kinetics of four biomarkers in plasma in patients admitted to ICU including sepsis and during antibiotics treatment. Methods The biomarkers evaluated were HBP (Heparin-binding protein), HNL Dimer (Human Neutrophil Lipocalin), HNL Total and PCT (Procalcitonin). Plasma was obtained at admission to ICU and during follow-up at days 2 and 3. Antibiotic treatment was started or reviewed on admission to ICU. The results were compared to SOFA and KDIGO-scores and to survival. 277 patients admitted to ICU were included of which 30% had sepsis. The other groups were categorized as miscellaneous, other medical and trauma. Results The plasma concentrations of all four biomarkers were highly elevated with the highest concentrations in sepsis patients. During the follow-up period HNL Dimer decreased already day 2 and further so day 3 (p…

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

ObjectiveThis study compared the costs and nursing time associated with the delivery of continuous infusion of antibiotics via elastomeric infusion pumps (EIP) versus conventional intermittent infusion (CII) across different care pathways. DesignRetrospective real-world data informed a cost comparison analysis that compared costs and nursing hours between infusion of antibiotics via EIP versus CII across eight care pathways in inpatient or outpatient care during infection episodes. Real-world data were obtained from patients treated within a year with parenteral antimicrobial therapy in Päijät-Häme Region, Finland. SettingInpatient care with hospital admission and outpatient care at hospital at home in Päijät-Häme Region in Finland. Participants3778 patients with a total of 4214 infection episodes treated with intravenous antimicrobial therapy. InterventionsEight treatment strategies with various combinations of EIP and CII administered in inpatient or outpatient care. Primary and secondary outcome measuresDirect costs and nursing time. ResultsSkin and soft tissue infections accounted for the highest number of episodes treated with EIP overall (30.8%; 74 out of 240 episodes) and in outpatient care specifically (53.3%; 128 out of 240 episodes). Compared with inpatient care costs with CII (4590 per episode), treating skin and soft tissue infections in outpatient care with EIP or CII incurred only 24% (1104) and 35% (1620) of the costs, respectively. Across all treatment strategies and infections studied, the use of EIP consistently required less nursing time. The highest nursing time in the outpatient care was observed in sepsis episodes treated with CII (37 hours with CII vs 7 hours with EIP per episode). ConclusionDelivery of antimicrobial therapy using continuous infusions with EIP instead of CII can significantly decrease the nursing time and cost in both inpatient and outpatient care. For skin and soft tissue infections and sepsis, the utilisation of EIP is a cost-saving option in outpatient care compared with the use of CII. …

Objectives: To determine the frequency of and risk factors for increased post-sepsis healthcare utilization compared with pre-sepsis healthcare utilization. Design: Retrospective observational cohort study. Setting: Years 2016–2019 MarketScan Commercial and Medicaid Database. Patients: Children (0–18 yr) with sepsis treated in a U.S. hospital. Interventions: None. Measurements and Main Results: We measured the frequency of and risk factors for increased healthcare utilization in the 90 days post- vs. pre-sepsis hospitalization. We defined increased healthcare utilization as an increase of at least 3 days in the 90 days post-hospitalization compared with the 90 days pre-hospitalization based on outpatient, emergency department, and inpatient hospitalization. We identified 2801 patients hospitalized for sepsis, of whom 865 (30.9%) had increased healthcare utilization post-sepsis, with a median (interquartile range [IQR]) of 3 days (1–6 d) total in the 90 days pre-sepsis and 10 days (IQR, 6–21 d) total in the 90 days post-sepsis (p < 0.001). In multivariable models, the odds of increased healthcare use were higher for children with longer lengths of hospitalization (> 30 d adjusted odds ratio [aOR], 4.35; 95% CI, 2.99-6.32) and children with preexisting complex chronic conditions, specifically renal (aOR, 1.47; 95% CI, 1.02–2.12), hematologic/immunologic (aOR, 1.34; 95% CI, 1.03–1.74), metabolic (aOR, 1.39; 95% CI, 1.08–1.79), and malignancy (aOR, 1.89; 95% CI, 1.38–2.59). Conclusions: In this nationally representative cohort of children who survived sepsis hospitalization in the United States, nearly one in three had increased healthcare utilization in the 90 days after discharge. Children with hospitalizations longer than 30 days and complex chronic conditions were more likely to experience increased healthcare utilization.

Objectives: To characterize associations between race/ethnicity/sex, time-to-antibiotics, and mortality in patients with suspected sepsis or septic shock. Design: Retrospective cohort study, with race/ethnicity/sex as the exposure, and time-to-antibiotics (relative to emergency department arrival) and in-hospital mortality as the outcome. Setting: Five Massachusetts hospitals. Patients: Forty-nine thousand six hundred nine adults admitted 2015–2022 with suspected sepsis or septic shock (blood cultures drawn and IV antibiotics administered within 24 hr of arrival, plus evidence of organ dysfunction for sepsis, and hypotension or lactate ≥ 4.0 mmol/L for septic shock). Interventions: None. Measurements and Main Results: Among included patients, 22,598 (46%) were women, 36,626 (75%) were White, and 4,483 (9.2%) were Black. Women had longer median time-to-antibiotics than men when presenting with either suspected sepsis (203 vs. 190 min) or septic shock (160 vs. 142 min). Differences in time-to-antibiotics for women vs. men persisted after adjusting for age, race, comorbidities, source of infection, and severity of illness (adjusted odds ratio [aOR] for 3–6 vs. < 3 hr; 1.16 [95% CI, 1.07–1.25] for sepsis and aOR, 1.09 [95% CI, 1.01–1.18] for septic shock). Median time-to-antibiotics was also longer for Black vs. White patients for both sepsis (215 vs. 194 min; aOR for 3–6 vs. < 3 hr; 1.24 [95% CI, 1.06–1.45]) and septic shock (median 159 vs. 148 min; aOR, 1.32 [95% CI, 1.12–1.55]). There was no association between race/ethnicity/sex and in-hospital mortality for sepsis without shock; however, women with septic shock had higher mortality (aOR, 1.16; 95% CI, 1.04–1.29) vs. men. Higher mortality for women with septic shock persisted when also adjusting for time-to-antibiotics (aOR, 1.16; 95% CI, 1.03–1.32). Conclusions: In a large cohort of patients with sepsis, time-to-antibiotics was longer for both women and Black patients even after detailed risk-adjustment. Women with septic shock had higher adjusted in-hospital mortality than men, but this association was not moderated by time-to-antibiotics.

Objectives: The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scvo2) in estimating mixed venous oxygen saturation (Svo2) and cardiac index in critically ill patients. Data Sources: A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024. Study Selection: Studies of patients in the ICU for whom Scvo2 and at least one reference standard test was performed (thermodilution and/or Svo2) were included. Data Extraction: Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Svo2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments. Data Synthesis: Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Svo2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Svo2 was 0.83 (95% CI, 0.75–0.89) with a mean difference of 2.98% toward Scvo2. The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46–0.48; p < 0.0001). Conclusions: There is moderate reliability for Scvo2 in predicting Svo2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scvo2 in predicting cardiac index.

Objectives: Pediatric sepsis-associated acute kidney injury (AKI) often requires continuous renal replacement therapy (CRRT), but limited data exist regarding patient characteristics and outcomes. We aimed to describe these features, including the impact of possible dialytrauma (i.e., vasoactive requirement, negative fluid balance) on outcomes, and contrast them to nonseptic patients in an international cohort of children and young adults receiving CRRT. Design: A secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), an international, multicenter, retrospective study. Setting: Neonatal, cardiac and PICUs at 34 centers in nine countries from January 1, 2015, to December 31, 2021. Patients: Patients 0–25 years old requiring CRRT for AKI and/or fluid overload. Interventions: None. Measurements and Main Results: Among 1016 patients, 446 (44%) had sepsis at CRRT initiation and 650 (64%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (defined as a composite of death, renal replacement therapy [RRT] dependence, or > 25% decline in estimated glomerular filtration rate from baseline at 90 d from CRRT initiation). Septic patients were less likely to liberate from CRRT by 28 days (30% vs. 38%; p < 0.001) and had higher rates of MAKE-90 (70% vs. 61%; p = 0.002) and higher mortality (47% vs. 31%; p < 0.001) than nonseptic patients; however, septic survivors were less likely to be RRT dependent at 90 days (10% vs. 18%; p = 0.011). On multivariable regression, pre-CRRT vasoactive requirement, time to negative fluid balance, and median daily fluid balance over the first week of CRRT were not associated with MAKE-90; however, increasing duration of vasoactive requirement was independently associated with increased odds of MAKE-90 (adjusted OR [aOR], 1.16; 95% CI, 1.05–1.28) and mortality (aOR, 1.20; 95% CI, 1.1–1.32) for each additional day of support. Conclusions: Septic children requiring CRRT have different clinical characteristics and outcomes compared with those without sepsis, including higher rates of mortality and MAKE-90. Increasing duration of vasoactive support during the first week of CRRT, a surrogate of potential dialytrauma, appears to be associated with these outcomes.

Abstract Purpose The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient\'s life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. Patients and methods From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital\'s computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. Results Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. Conclusion Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions. …

by Daniel Geleta, Gemeda Abebe, Tsion Tilahun, Didimos Gezahegn, Netsanet Workneh, Getenet Beyene Background Epidemiological profiles and the rundown crisis of antimicrobial resistance from bacterial isolates in neonatal sepsis compel regular surveillance to enhance data-driven decision-making. Accordingly, this study aimed to assess the phenotypic epidemiology and antimicrobial resistance profiles of bacteria isolated from clinically suspected neonatal sepsis in Ethiopia. Methods A total of 342 neonates suspected of clinical sepsis were randomly included in a prospective observational study conducted at the neonatal intensive care unit (NICU) of Jimma medical center (JMC) from May 2022 to July 2023. Blood samples were collected from each neonate and subjected to a culture test for identification of bacterial isolates and their antibiotic resistance profiles following the standardized guidelines. The laboratory results, along with relevant clinical data, were recorded using WHONET and analyzed using STATA software. Results Out of the 342 blood samples that were analyzed, 138 samples (40.4%, 95% CI: 35.1–45.6, P…

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, β was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

Publication date: Available online 20 July 2023 Source: Immunity Author(s): Hang Thi Thuy Gander-Bui, Joëlle Schläfli, Johanna Baumgartner, Sabrina Walthert, Vera Genitsch, Geert van Geest, José A. Galván, Carmen Cardozo, Cristina Graham Martinez, Mona Grans, Sabine Muth, Rémy Bruggmann, Hans Christian Probst, Cem Gabay, Stefan Freigang …