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Background: Sepsis is one of the major causes of morbidity and mortality in burn patients. However, the optimal timing of admission which can minimize the probability of sepsis is still unclear. This study aims to determine the optimal time period of admission for severely burned patients and find out the possible reasons for it., Method: 185 victims to the Kunshan factory aluminum dust explosion accident, which happened on August 2nd, 2014, were studied. The optimal cutpoint for continuous variables in survival models was determined by means of the maximally selected rank statistic. Univariate and multivariate analyses were further conducted to verify that admission time was not a risk factor for sepsis. Subgroup analyses were performed to find out possible contributing factors for the result., Result: The cutoff point for admission time was determined as seven hours, which was supported by the survival curve (p < 0.001). Multivariate analysis showed that, in our study population, delayed admission time was not a risk factor for sepsis (HR = 0.610, 95 %CI = 0.415 - 0.896, p = 0.012). Subgroup analyses showed that "Tracheotomy before admission" (p = 0.002), "Whole blood transfusion" (p < 0.001), "Hemodynamic instability before admission" (p = 0.02), "Has a burn department in the hospital" (p = 0.009), "Has a burn ICU in the hospital" (p < 0.001), "Acute heart failure (AHF)" (p = 0.05), "acute respiratory distress syndrome (ARDS)" (p = 0.05) and "GI bleeding" (p = 0.04) were all statistically significant., Conclusion: In our study population, we found that delayed admission time was not a risk factor associated with a reduced incidence of sepsis among severely burned patients. This might be attributed to variations in prehospital treatments (whole blood transfusion and tracheotomy), whether the hospital had a burn department/ICU, and certain complications (AHF, ARDS and GI bleeding). It can be inferred that early prehospital care plays a crucial role in reducing sepsis risk among severe burn patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Introduction: Streptococcus pneumoniae, a commensal in the nasopharynx, can cause invasive pneumococcal diseases (IPDs). To prevent the aggravation of IPDs, it is important to enhance host immune defense against S. pneumoniae. Hochuekkito (HET) is expected to have an immunostimulatory effect against infections., Methods: HET was administrated by gavage to adult BALB/cA mice before and after intranasal inoculation of S. pneumoniae. We evaluated the effect of HET on pneumococcal nasal colonization and subsequent development of lethal pneumococcal infections., Results: No effect on nasal colonization was observed, but HET significantly reduced bacterial count in the blood, decreased the incidence of bacteremia, and improved survival. HET also reduced nasal tissue damage 3 days after intranasal infection. Neutrophils from HET-treated mice showed significantly higher bactericidal activity against S. pneumoniae in the presence of the serum from the HET group compared with from the control group., Conclusions: The non-specific immunostimulatory effect of HET is suggested by this study to be effective in preventing the progression in IPDs and provided insights into novel strategy in the post-pneumococcal vaccine era., Competing Interests: Declaration of competing interest K Ogura is an employee of Tsumura & Co. M Hotomi received a research grant from Tsumura & Co. The remaining authors have no conflicts of interest. The funder was involved in the study design, interpretation of data, or the writing of this article., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Whether antibiotic de-escalation reduces the risk of subsequent antibiotic resistance is uncertain. We sought to determine if beta-lactam (BL) antibiotic de-escalation is associated with decreased incidence of new Gram-negative resistance in hospitalized patients with sepsis., Methods: In a retrospective cohort study, patients with sepsis who were treated with at least 3 consecutive days of BL antibiotics, the first 2 days of which were with a broad-spectrum BL agent defined as a spectrum score (SS) of ≥7 were enrolled. Patients were grouped into three categories: (1) de-escalation of beta-lactam spectrum score (BLSS), (2) no change in BLSS, or (3) escalation of BLSS. The primary outcome was the isolation of a new drug-resistant Gram-negative bacteria from a clinical culture within 60 days of cohort entry. Fine-Gray proportional hazards regression modeling while accounting for in-hospital death as a competing risk was performed., Findings: Six hundred forty-four patients of 7742 (8.3%) patients developed new gram-negative resistance. The mean time to resistance was 23.7 days yielding an incidence rate of 1.85 (95% confidence interval [CI]: 1.71-2.00) per 1000 patient-days. The lowest incidence rate was observed in the de-escalated group 1.42 (95% CI: 1.16-1.68) per 1000 patient-days. Statistically significant reductions in the development of new gram-negative resistance were associated with BL de-escalation compared to no-change (hazards ratio (HR) 0.59 [95% CI: .48-.73])., Conclusions: De-escalation was associated with a decreased risk of new resistance development compared to no change. This represents the largest study to date showing the utility of de-escalation in the prevention of antimicrobial resistance., Competing Interests: Potential conflicts of interest. M. H. K.’s efforts were supported by the Barnes-Jewish Hospital Foundation. B. F. T.’s contribution occurred while he was working at the University of Health Sciences and Pharmacy in St. Louis; he is now an employee of Melinta Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: A new medical device was developed for multi-infusion in neonatal intensive care units (NICUs) with the aim of addressing issues related to drug incompatibilities and central-line-associated bloodstream infections (CLABSIs)., Aim: To assess the cost-effectiveness of implementing this new perfusion system in an NICU setting., Methods: This single-centre, observational study was conducted in all infants admitted to the NICU within 3 days of birth, and who required a central venous line, to evaluate the cost and effectiveness before (2019) and after (2020) implementation of the new perfusion system. Costs were calculated from the hospital perspective, and the incidence of CLABSIs was examined over a time horizon from NICU admission to discharge. Resource utilization was measured (infusion device, infection-treating drugs and biological analyses), and corresponding costs were valued using tariffs for 2019. The incremental cost-effectiveness ratio (ICER) was calculated, expressed as Euros per CLABSI avoided, and one-way and multi-variate sensitivity analyses were conducted., Findings: Among 609 infants selected, clinical characteristics were similar across both periods. The CLABSI rate decreased significantly (rate ratio 0.22, 95% confidence interval 0.07-0.56), and total costs reduced from €65,666 to €63,932 per 1000 catheter-days (P<0.001) after implementation of the new perfusion system, giving an ICER of €251 saved per CLABSI avoided. The majority of sensitivity analyses showed that the new intervention remained economically dominant., Conclusion: This single-centre study showed a significant decrease in the incidence of CLABSIs after implementation of the new perfusion system, without incurring additional costs. Further prospective multi-centre randomized studies are needed to confirm these results in other NICUs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In the past, we demonstrated that oligodeoxynucleotides containing CpG motifs (CpG-ODN) mimicking bacterial DNA, stimulate the innate immune system of neonatal broiler chickens and protect them against Escherichia coli and Salmonella Typhimurium (S. Typhimurium) septicemia. The first line of innate immune defense mechanism is formed by heterophils and plays a critical protective role against bacterial septicemia in avian species. Therefore, the objectives of this study were 1) to explore the kinetics of CpG-ODN mediated antibacterial mechanisms of heterophils following single or twice administration of CpG-ODN in neonatal broiler chickens and 2) to investigate the kinetics of the immunoprotective efficacy of single versus twice administration of CpG-ODN against S. Typhimurium septicemia. In this study, we successfully developed and optimized flow cytometry-based assays to measure phagocytosis, oxidative burst, and degranulation activity of heterophils. Birds that received CpG-ODN had significantly increased (p < 0.05) phagocytosis, oxidative burst, and degranulation activity of heterophils as early as 24 h following CpG-ODN administration. Twice administration of CpG-ODN significantly increased the phagocytosis activity of heterophils. In addition, our newly developed CD107a based flow cytometry assay demonstrated a significantly higher degranulation activity of heterophils following twice than single administration of CpG-ODN. However, the oxidative burst activity of heterophils was not significantly different between birds that received CpG-ODN only once or twice. Furthermore, delivery of CpG-ODN twice increased immunoprotection against S. Typhimurium septicemia compared to once but the difference was not statistically significant. In conclusion, we demonstrated enhanced bactericidal activity of heterophils after administration of CpG-ODN to neonatal broiler chickens. Further investigations will be required to identify other activated innate immune cells and the specific molecular pathways associated with the CpG-ODN mediated activation of heterophils., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Premature infants have higher risks of infection due to their underdeveloped immune systems and changes to the oral cavity's normal flora colonization., Purpose: To assess the effect of oral colostrum application on the condition of the mouth and the incidence of late-onset sepsis (LOS) among premature infants., Methods: In this randomized controlled trial, 70 newborn premature infants were randomly allocated to colostrum or sterile water groups. The Mouth Care Assessment Tool was used to evaluate the condition of the mouth for 5 days after oral colostrum application. The incidence of LOS was measured using clinical and laboratory indicators from 72 hours after birth until discharge., Results: The condition of the mouth was significantly different on days 4 and 5, demonstrating that the colostrum group had less need for oral care ( P < .001) compared to the control group. There was no significant difference between the 2 groups in clinical symptoms and laboratory values related to LOS ( P > .05)., Implications for Practice: Oral colostrum application can benefit oral mucosal health and reduce the need for oral care among premature infants. It is also safe alternative oral care for premature infants who cannot breastfeed during the first few days of life. Future research should include infants of different gestational ages and mechanically ventilated infants to assess the effect of oral colostrum application on serum immune factors., (Copyright © 2024 by The National Association of Neonatal Nurses.)

We conducted a quality improvement project from 2019 to 2021 at a single home health agency to reduce rates of central line-associated bloodstream infection in our ambulatory pediatric population. Annualized central line-associated bloodstream infection rates per 1,000 catheter line days decreased by 20 % during the study period, from a rate of 1.023 to 0.810. This decrease was sustained in the 10-month post-study period with a center line shift of 1.090 to 0.658., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Preterm birth significantly contributes to mortality and morbidities, with recent studies linking these issues to gut microbiota imbalances. Probiotic supplementation shows promise in mitigating adverse outcomes in preterm infants, but optimal timing and guidelines remain unclear. This study assesses the benefits of probiotic supplementation for preterm infants without consistent guidelines. Methods: This retrospective study examined extremely low-birth-weight (ELBW) infants in neonatal intensive care units from 2017 to 2021. Mortality and preterm-related outcomes were compared between infants receiving probiotics and those not. Subgroup analyses based on probiotic initiation timing were conducted: early (≤14 days), late (>14 days), and non-probiotic groups. Results: The study included 330 ELBW infants: 206 received probiotics (60 early, 146 late), while 124 did not. Probiotic supplementation was associated with lower overall mortality (adjusted OR 0.22, 95% CI 0.09-0.48) and decreased mortality from necrotizing enterocolitis (NEC) or late-onset sepsis (LOS) (adjusted OR 0.12, 95% CI 0.03-0.45). Early probiotics reduced overall mortality, NEC/LOS-related mortality, and NEC/LOS-unrelated mortality. Late probiotics decreased overall mortality and NEC/LOS-related mortality. Early probiotic use also expedited full enteral feeding achievement. Conclusions: Probiotic supplementation reduces mortality and improves feeding tolerance in preterm infants. Establishing guidelines for probiotic use in this population is crucial.

Objective: To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies. Methods: Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA). Results: A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography ( OR= 0.26, 0.27; 95% CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery ( OR= 0.43, 0.44; 95% CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI ( OR= 0.58, 0.52; 95% CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z -curve for balanced solution (cumulative Z= 3.38) crossed the TSA monitoring boundary ( Z= 3.29). Conclusion: Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

Sepsis is a leading cause of death in preterm neonates. The increased susceptibility to sepsis is due to prolonged hospitalization, the need for invasive procedures, and immaturity of innate and adaptive immunity. Chlorhexidine gluconate is a popular topical disinfectant that was not recommended for use in preterm neonates until 2012. Thus, there are few studies assessing the role of chlorhexidine gluconate in antisepsis for preterm neonates. A better understanding of the safety and efficacy of chlorhexidine gluconate as an antiseptic agent for preterm neonates is the first step in establishing best practice guidelines for this population., (© 2024 Wiley Periodicals LLC.)

Background: Sepsis is a critical situation, and its treatment and reduction are important clinical issues. Antibiotics are a routine treatment option, but their adverse effects are a concern in pediatric patients, especially infants. Prebiotics might be an alternative option., Objectives: The aim of this study was to provide an updated systemic review and meta-analysis of randomized controlled trials (RCTs) on the use of prebiotics for sepsis in infants, which could assist clinicians in deciding whether to use this treatment., Methods: The study included RCTs related to prebiotics and sepsis in infants. A random effects model and the odds ratio (OR) were applied to estimate the effect of prebiotic use and the incidence of sepsis in infants. The analysis included 16 studies with a total of 6,438 infants. The primary outcome was the OR of sepsis for infants who received prebiotics., Results: The results of the meta-analysis demonstrated that the pooled OR of sepsis was significantly lower for infants who used prebiotics. However, the results indicated a medium level of heterogeneity., Conclusion: The results showed that the use of prebiotics might be associated with a reduction of sepsis in infants. The standardized application of this treatment might be an intriguing topic for future clinical research.

Background: Hospital-acquired complications add to patient morbidity and mortality, costs, length of stay, and negative patient experience. Patient Safety Indicators (PSIs) are a validated and widely used metric to evaluate hospital administrative data on preventing these events. Although many studies have addressed PSI validity, few have aimed to reduce PSI through clinical care. The authors aimed to reduce PSI events by addressing both validity and clinical care., Methods: Frontline clinicians used a deep dive template to provide input on all PSI cases, which were then reviewed by a PSI task force to identify performance gaps. After analyzing the frequency of gaps and cost-vs.-impact of potential solutions, five interventions were implemented to address the three most common, highly weighted PSIs: pressure ulcers, postoperative venous thromboembolism (VTE), and postoperative sepsis. Clinical care interventions included increasing patient mobility by creating a specialized mobility technician position, skin care audits to prevent pressure ulcers, and increasing use of pharmacologic VTE prophylaxis. Administrative interventions addressed improving clinician-coding concordance for sepsis and increasing documentation of comorbidities., Results: After interventions, the number of PSI events for composite PSI, VTE, and sepsis decreased by 41.3% (p = 0.039), 85.2% (p = 0.0091), and 51.5% (p = 0.063), respectively, relative to the preintervention period. Pressure ulcers increased by 33.3% (p = 0.0091)., Conclusion: Hospital complications cause substantial burden to hospitals, patients, and caregivers. Addressing administrative and clinical factors with targeted interventions led to reduction in composite PSI. Further efforts are needed locally to reduce the pressure ulcer PSI., (Published by Elsevier Inc.)

Introduction: This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature neonates. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks of gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period from January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis, mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially of Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher necrotising enterocolitis, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment duration for preterm infants to achieve the health benefits identified.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) can promote antimicrobial immunity in chickens by enriching immune compartments and activating immune cells. Innate memory, or trained immunity, has been demonstrated in humans and mice, featuring the absence of specificity to the initial stimulus and subsequently cross-protection against pathogens. We hypothesize that CpG-ODN can induce trained immunity in chickens. We delivered single or multiple administrations of CpG-ODN to birds and mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis of peripheral blood mononuclear cells were quantified using Seahorse XFp. Next, chickens were administered with CpG-ODN twice at 1 and 4 day of age and challenged with Escherichia coli at 27 days of age. The CpG-ODN administered groups had significantly higher mitochondrial OXPHOS until 21 days of age while cellular glycolysis gradually declined by 14 days of age. The group administered with CpG-ODN twice at 1 and 4 days of age had significantly higher survival, lower clinical score and bacterial load following challenge with E. coli at 27 d of age. This study demonstrated the induction of trained immunity in broiler chickens following administration of CpG-ODN twice during the first 4 days of age to protect birds against E. coli septicemia at 27 days of age., (© 2024. Crown.)

Background: Sepsis is a life-threatening and relatively common emergency which is often recognized too late or not at all. Therefore, the "SepsisWissen" (SepsisKnowledge) project aimed to bring about changes in health care professionals' behavior in the area of sepsis prevention and early detection. It addressed the health care professionals themselves (e. g., their own vaccination, hygiene and early detection behavior) and their patient counseling behavior. To promote this behavior, the SepsisWissen campaign included offers such as trainings or print products. The subsequent core question is: From the health professionals' perspective, which barriers and facilitators affect their own application of sepsis competence and their promotion of their patients' sepsis competence?, Methods: This paper was based on a cross-sectional mixed-methods study part of "SepsisWissen" withPart a) was analyzed using qualitative oriented content analysis based on Mayring, part b) was analyzed descriptively. The interviewees included physicians, nurses, pharmacists, assistants to physicians and pharmacists and, additionally, one paramedic in the quantitative sample. Some of them had attended "SepsisWissen" trainings., Results: The qualitative data analysis identified 41 conducive and hindering factors, which can be assigned to the following eight major topics: 1) syndrome sepsis; 2) predisposing factors for health professionals' own acquisition and application of sepsis competence; 3) enabling factors for health professionals themselves; 4) behavior and lifestyle of patients; 5) reinforcing factors for patients; 6) public health education; 7) political, administrative, and organizational context; 8) environmental factors. In the qualitative and quantitative surveys, the suggestion to improve the sepsis competence of the population and to reduce misinformation, respectively, through public education (e.g., via schools or the media)., Discussion: Sepsis training for health professionals was considered as a facilitating factor for taking potential sepsis symptoms and patients' respective statements more seriously. Future training formats should convey more explicitly how health professionals can better communicate their own sepsis knowledge to their patients. They request instruments to support their communication, such as checklists for lay persons. According to the interviews, health workers themselves need recurring external reminders for the topic of sepsis. Organizational and political conditions should be improved. From the health professionals' point of view, it is essential to offer better reimbursement for prevention and counseling services and to allocate adequate time resources for both., Conclusion: Health professionals could increase their potential to apply and promote sepsis competence if general conditions were optimized. From their perspective, it is most important to relieve them of some of their patient counselling burden by initiating more public education., (Copyright © 2024. Published by Elsevier GmbH.)

Objective: To investigate adherence to intravascular catheter (IVC) insertion and maintenance guidelines in Chinese tertiary hospitals., Methods: A cross-sectional questionnaire survey of adult inpatients with IVC placements was conducted from July to September 2022 in 20 tertiary hospitals in China. One clinical staff member from each department in each hospital was assigned to participate in the survey. Questionnaires were uniformly collected and reviewed after three months., Results: This study included 1815 cases (62.69%) of central venous catheter, 471 cases (16.27%) of peripherally inserted central catheter, 461 cases (15.92%) of PORT, and 147 cases (5.08%) of haemodialysis catheter insertions. Statistically significant differences in compliance were observed across the four IVC types, specifically in relation to the insertion checklist, standard operating procedure, and insertion environment (P<0.05). Practice adherence during IVC maintenance differed significantly across the four IVC types in aspects such as availability of IVC maintenance verification forms, daily scrubbing of the catheterized patients, and catheter connection methods (P<0.05). A total of 386 (13.34%) patients developed fever, 1086 (37.53%) were treated with therapeutic antibiotics, 16 (0.55%) developed central-line-associated bloodstream infections, two (0.07%) developed local skin infections, and six (0.21%) developed deep vein thrombosis., Conclusions: Adherence to guidelines regarding insertion and maintenance differed across the four IVC types; there is a gap between the recommended measures and the actual operation of the guidelines. Therefore, it is necessary to further enhance training and develop checklists to prevent central-line-associated bloodstream infections., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pseudomonas aeruginosa is a complex nosocomial infectious agent responsible for numerous illnesses, with its growing resistance variations complicating treatment development. Studies have emphasized the importance of virulence factors OprE and OprF in pathogenesis, highlighting their potential as vaccine candidates. In this study, B-cell, MHC-I, and MHC-II epitopes were identified, and molecular linkers were active to join these epitopes with an appropriate adjuvant to construct a vaccine. Computational tools were employed to forecast the tertiary framework, characteristics, and also to confirm the vaccine's composition. The potency was weighed through population coverage analysis and immune simulation. This project aims to create a multi-epitope vaccine to reduce P. aeruginosa-related illness and mortality using immunoinformatics resources. The ultimate complex has been determined to be stable, soluble, antigenic, and non-allergenic upon inspection of its physicochemical and immunological properties. Additionally, the protein exhibited acidic and hydrophilic characteristics. The Ramachandran plot, ProSA-web, ERRAT, and Verify3D were employed to ensure the final model's authenticity once the protein's three-dimensional structure had been established and refined. The vaccine model showed a significant binding score and stability when interacting with MHC receptors. Population coverage analysis indicated a global coverage rate of 83.40%, with the USA having the highest coverage rate, exceeding 90%. Moreover, the vaccine sequence underwent codon optimization before being cloned into the Escherichia coli plasmid vector pET-28a (+) at the EcoRI and EcoRV restriction sites. Our research has developed a vaccine against P. aeruginosa that has strong binding affinity and worldwide coverage, offering an acceptable way to mitigate nosocomial infections., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Annually, sepsis leads to approx. 90.000 deaths in Germany. Risk factors include amongst others older age (>60), innate or acquired dysfunction of the immune system, and underlying chronic diseases of the lung, heart, liver, or kidneys. The manifestation of sepsis is a medical emergency, and patient outcomes depend on timely diagnosis and immediate treatment. In addition, vaccinations e.g., against pneumococci or influenza virus, are a highly effective public health tool to prevent the most common underlying infections that may lead to sepsis. However, a lack of public awareness for the relevance of vaccination and detecting sepsis as an emergency underlines the need for public health interventions that address these issues. SepWiss aims to evaluate the effects of a multimodal information campaign designed to address this lack of awareness among the risk population in Germany., Methods: SepWiss is an intervention at state level, consisting of a multimodal information campaign targeting risk groups in the German federal states of Berlin and Brandenburg (intervention region). Based on available evidence, various information formats were developed and implemented by outdoor advertising, social media, educational formats and through stakeholders' platforms, starting in August 2021. The control region comprises of the remaining 14 German federal states. We will analyze vaccination coverage (primary outcome), and sepsis knowledge, the ability to detect sepsis as an emergency, and attitude towards vaccination (secondary outcomes) amongst the risk population in a controlled before-after comparison. The implementation is accompanied by a mixed-method process evaluation., Discussion: SepWiss is the first project of its kind to evaluate a complex multi-faceted evidence-based information campaign with regards to the topics of vaccination coverage, and the importance of sepsis detection and prevention for the most vulnerable populations in Germany. Results will be valuable for informing further nationwide campaigns., Trial Registration: German Registry for Clinical Trials: DRKS00024475. Registered February 24th, 2021., Competing Interests: The authors declare that no competing interests exist within this study protocol and the funding received by the innovation fund., (Copyright: © 2024 Abels et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The microbiota in the intestine is made up of trillions of living bacteria that coexist with the host. Administration of antibiotics during neonatal infection causes depletion of gut flora resulting in gut dysbiosis. Over the last few decades, probiotics have been created and promoted as microbiota management agents to enrich gut flora. Probiotics decrease the overgrowth of pathogenic bacteria in the gut of preterm neonates, reducing the frequency of nosocomial infections in the Neonatal Intensive Care Unit (NICUs). Methods: The systematic review will include randomized control trials (RCTs) of premier neonates with sepsis. Studies will be retrieved from global databases like Cochrane CENTRAL, CINAHL Plus via EBSCO host, MEDLINE via PubMed, EMBASE, SCOPUS, Ovid, Web of Science, ProQuest Medical Library, Microsoft academic, and DOAJ by utilizing database-specific keywords. Screening, data extraction, and critical appraisal of included research will be carried out separately by two review writers. Findings will be reported in accordance with the PRISMS-P 2020 guidelines. Conclusions: The findings of this systematic review will help to translate the evidence-based information needed to encourage the implementation of potential research output in the field of neonatal intensive care, guide best clinical practise, assist policy making and implementation to prevent gut dysbiosis in neonates with sepsis by summarising and communicating the evidence on the topic. PROSPERO registration number: This systematic review protocol has been registered in PROSPERO (Prospective Register of Systematic Reviews) on 10 th March 2022. The registration number is CRD42022315980., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Iqbal F et al.)

Background: Probiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain-specific effects and interactions facilitated by the use of combination species., Aims: To compare clinical outcomes of very preterm infants receiving multi or single-species probiotics., Study Design: Retrospective, single-center, cohort study., Subjects: Very preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi-species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single-species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation., Main Outcome Measures: NEC, LOS, and mortality., Results: The overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi-species and single-species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290)., Conclusion: The clinical outcomes of very preterm newborns receiving multi vs. single-species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Central line-associated bloodstream infections (CLABSIs) pose a significant risk to critically ill patients, particularly in intensive care units (ICU), and are a significant cause of hospital-acquired infections. We investigated whether implementation of a multifaceted intervention was associated with reduced incidence of CLABSIs., Methods: This was a prospective cohort study over nine years. We implemented a bundled intervention approach to prevent CLABSIs, consisting of a comprehensive unit-based safety program (CUSP). The program was implemented in the Neonatal ICU, Medical ICU, and Surgical ICU departments at the Aga Khan University Hospital in Pakistan., Results: The three intervention ICUs combined were associated with an overall 36% reduction in CLABSI rates and a sustained reduction in CLABSI rates for > a year (5 quarters). The Neonatal ICU experienced a decrease of 77% in CLABSI rates lasting ∼1 year (4 quarters). An attendance rate above 88% across all stakeholder groups in each CUSP meeting correlated with a better and more sustained infection reduction., Conclusions: Our multifaceted approach using the CUSP model was associated with reduced CLABSI-associated morbidity and mortality in resource-limited settings. Our findings suggest that a higher attendance rate (>85%) at meetings may be necessary to achieve sustained effects post-intervention., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To compare survival without BPD among extremely preterm infants (EPI) who received prophylactic early low-dose hydrocortisone (PEH) with those who did not (non-PEH)., Study Design: This single-center retrospective study compared risk-adjusted rates of survival without BPD, BPD, bowel perforation, and late-onset sepsis among infants (22-27 weeks' gestation at birth) who received PEH (n = 82) and who did not (n = 205)., Results: Infants in the PEH group were of lower gestational age, lower birthweight, and higher day-1 risk of death/BPD. After adjusting for risk of death/BPD, PEH-treated infants demonstrated increased survival without BPD (aOR 2.04, 95%CI 1.1-3.7), and lower BPD rates (aOR 0.46, 95%CI 0.25-0.87). Importantly, bowel perforation or sepsis rate were similar among both groups., Conclusion: After risk adjustment, PEH-treated infants demonstrated improved survival without BPD and did not increase rates of bowel perforation or sepsis. In our cohort of infants, PEH was safe and effective among the sickest preterm neonates., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Human milk is the preferred source of enteral nutrition for very low birthweight (VLBW) infants, and it possibly decreases dependence on parenteral nutrition (PN) and reduces incidence of late-onset sepsis (LOS). No systematic review to date has specifically addressed the value of early versus late introduction of human milk diet (HMD) on duration of PN and incidence of LOS among VLBW infants. Objective: To review the evidence for an early versus late introduction of HMD on duration of PN and incidence of LOS in VLBW infants. Method: Preferred reporting items for systematic reviews and meta-analysis-guided search of EMBASE and PubMed/Medline databases was conducted for this systematic review using phrases addressing population, intervention, comparator, and outcome framework to identify articles published over the past two decades without language restrictions. Full-text articles (both observational and randomized) that studied an early versus late initiation of HMD were included. Mean difference (MD) and relative risk (RR) with 95% confidence intervals (CIs) were calculated for PN and LOS. Quality of evidence was analyzed using UK National Service Framework and the risk-of-bias was assessed using Robvis ® . Results: One randomized controlled trial (RCT) and two observational studies (two English and one Chinese) recruited 474 VLBW infants (455 analyzed). Among an intrauterine growth-restricted cohort enrolled in the RCT ( n = 72), early HMD resulted in statistically significant reduction in PN dependence. However, no statistically significant difference was found in LOS. Two observational studies found similar reductions in PN duration and LOS incidence among the early HMD cohort. One observational study reported significant PN reduction; however, the incidence of LOS did not reach statistical significance in either case. Conclusion: An early HMD may reduce the duration of PN for a growth-restricted VLBW cohort. Observational studies suggesting reduced PN and LOS from early HMD endorse the need for bioactivity-focused human milk research. Variations in feeding guidelines among VLBW infants have the potential to influence neonatal outcomes significantly.

Purpose: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is associated with a 1-8% risk of post-biopsy sepsis (PBS). A recent study described an isopropyl alcohol needle washing protocol that significantly decreased PBS rates. The current study examined the efficacy of this technique in our clinic population., Materials and Methods: Data were reviewed for 1250 consecutive patients undergoing TRUS-Bx at the Charlie Norwood VA Medical Center from January 2017 to January 2023. Needle washing was adopted in February 2021. Complications occurring within 30 days after TRUS-Bx were recorded., Results: There were 912 patients in group 1 (without needle washing) and 338 in group 2 (with needle washing). Groups had equivalent demographic features, and men of African descent comprised 70% of patients. Standard 12 core biopsies were done in 83% and 82% in groups 1 and 2, respectively (p = 0.788). Total complication rates were 4% and 2% in groups 1 and 2, respectively (p = 0.077). There were 13 sepsis events in group 1 (1.4%) and none in group 2 (p = 0.027). Clavien-Dindo Grade I-III complications occurred in 25 (2.7%) and 7 (2.1%) patients in groups 1 and 2, respectively (p = 0.505). Standard antibiotic prophylaxis (PO fluoroquinolone and IM gentamicin) was given in 80% and 86% of patients in groups 1 and 2, respectively (p = 0.030). Subset analysis limited to patients who received standard prophylaxis showed a significant difference in sepsis rates (1.5% vs 0%; p = 0.036)., Conclusions: Adoption of isopropyl alcohol needle washing was associated with a significant decrease in PBS events., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother's own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods-41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64-1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis., Competing Interests: The authors declare no conflicts of interest.

Introduction: The use of oral azithromycin (AZI) as a preventive measure against postpartum infections of planned vaginal births has garnered a lot of interest in recent years and has been the subject of many randomized controlled trials (RCTs). However, the results from these trials have not been consistent. Therefore, we aim to perform a systematic review and meta-analysis to determine whether the use of a single-dose of oral AZI is clinically significant., Methods: We systematically searched PubMed, Embase, and Cochrane Central for RCTs from May to June 2023, comparing a single dose of oral AZI with placebo in patients undergoing planned vaginal delivery at a minimum of 28 weeks of gestational age. The main outcomes were puerperal and neonatal sepsis. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). Heterogeneity was assessed with I 2 statistics., Results: Four RCTs were included (mothers, n = 42 235; newborns n = 42 492). Approximately 49.8% of mothers received a single dose of oral AZI for sepsis prophylaxis. Compared with placebo, AZI significantly reduced the incidence of puerperal sepsis (risk ratio [RR], 0.65 [95% confidence interval (CI), 0.55-0.77]; P < 0.001), mastitis or breast abscess (RR, 0.58 [95% CI, 0.42-0.79]; P < 0.001), endometritis (RR, 0.65 [95% CI, 0.54-0.77]; P < 0.001), wound infection (RR, 0.81 [95% CI, 0.69-0.96]; P = 0.013), infection rate (RR, 0.62 [95% CI, 0.51-0.76]; P < 0.001), and fever (RR, 0.50 [95% CI, 0.28-0.89]; P = 0.018) in mothers. No statistically significant differences were identified between groups regarding maternal all-cause mortality and the use of prescribed postpartum antibiotics. Similarly, no statistical differences were noted in the neonatal group regarding sepsis, infection rate, and all-cause mortality., Conclusion: AZI appears to be an effective preventive measure against many postpartum infections in mothers but a substantial impact on neonatal outcomes has not yet been conclusively observed., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: This study explored rarely investigated organizational factors (resource support and organizational culture) in conjunction with well-established individual factors (demographic characteristics, knowledge, and awareness) that impact nurses' practice of central line-associated bloodstream infection (CLABSI) prevention., Methods: Self-reported questionnaire data were collected from 173 nurses recruited from departments that use central venous catheters (ie, intensive care units, emergency rooms, hemodialysis rooms, and oncology wards) in tertiary hospitals in South Korea. Multiple regression analyses were performed to examine the effects of individual and organizational factors., Results: Organizational culture (ß = 0.350) had the greatest association with CLABSI prevention practice, followed by awareness (ß = 0.328) and department (ß = -0.217; all ps < 0.01). These variables explained 41.1% of the variance in CLABSI prevention practice (F = 20.996, P < .001). Higher self-reported CLABSI prevention practice was associated with a favorable organizational culture and higher awareness. Emergency room nurses' CLABSI prevention practice was notably inferior as compared to nurses in other departments., Discussion: Organizational culture is the most significant factor affecting nurses' practice of CLABSI prevention., Conclusions: An organizational culture with environmental improvements and resource support as well as infection prevention education and awareness-building programs should be fostered., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns., Data Sources: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024., Methods: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity., Results: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I 2 , 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I 2 , 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I 2 , 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I 2 , 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I 2 , 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears., Conclusion: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms., (© 2024. The Author(s).)

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22 nd , 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention., Competing Interests: Declaration of competing interest Ping-Tao Tseng, Bing-Yan Zeng, Pin-Yang Yeh, Bing-Syuan Zeng, Brendon Stubbs, John S. Kuo, Cheuk-Kwan Sun, Yu-Shian Cheng, Yen-Wen Chen, Tien-Yu Chen, Yi-Cheng Wu, Yu-Kang Tu, Pao-Yen Lin, Dian-Jeng Li, Chih-Sung Liang, Mein-Woei Suen, Yi-Che Lee, Wei-Chieh Yang, Chih-Wei Hsu, Yow-Ling Shiue, and Kuan-Pin Su declared that there were no any competing interests existed., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Catheter-related sepsis (CRS) is a major complication with significant morbidity and mortality. Evidence is lacking regarding the most appropriate antiseptic for skin disinfection before percutaneous central venous catheter (PCVC) insertion in preterm neonates. To inform the feasibility and design of a definitive randomised controlled trial (RCT) of two antiseptic formulations, we conducted the Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) feasibility study to assess catheter colonisation, sepsis, and skin morbidity., Design: Feasibility RCT., Setting: Two UK tertiary-level neonatal intensive care units., Patients: Preterm infants born <34 weeks' gestation scheduled to undergo PCVC insertion., Interventions: Skin disinfection with either 2% chlorhexidine gluconate (CHG)-aqueous or 2% CHG-70% isopropyl alcohol (IPA) before PCVC insertion and at removal., Primary Outcome: Proportion in the 2% CHG-70% IPA arm with a colonised catheter at removal., Main Feasibility Outcomes: Rates of: (1) CRS, catheter-associated sepsis (CAS), and CRS/CAS per 1,000 PCVC days; (2) recruitment and retention; (3) data completeness., Safety Outcomes: Daily skin morbidity scores recorded from catheter insertion until 48 hours post-removal., Results: 116 babies were randomised. Primary outcome incidence was 4.1% (95% confidence interval: 0.9% to 11.5%). Overall catheter colonisation rate was 5.2% (5/97); CRS 2.3/1000 catheter days; CAS 14.8/1000 catheter days. Recruitment, retention and data completeness were good. No major antiseptic-related skin injury was reported., Conclusions: A definitive comparative efficacy trial is feasible, but the very low catheter colonisation rate would make a large-scale RCT challenging due to the very large sample size required. ARCTIC provides preliminary reassurance supporting potential safe use of 2% CHG-70% IPA and 2% CHG-aqueous in preterm neonates., Trial Registration Number: ISRCTN82571474., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Blood culture proven sepsis is associated with increased mortality and morbidity. Given the extended hospitalization of very preterm infants, catheter-related blood stream infections (CRBSIs) play a substantial role in sepsis. The reported incidence of CRBSIs in neonates varies from 3.2 to 21.8 CRBSIs per 1000 catheter line days. Moreover, discrepancies in neonatal practices and potential neglect may lead to the unwarranted prolongation of central lines. This study aims to compare two distinct periods (Pre-QI vs. Post-QI) in relation to the central line insertion rate and duration, as well as blood culture proven sepsis, duration of total parenteral nutrition (TPN), and the progression of feeding. These factors are known to be associated with prolonged hospitalization and increased morbidities. A total of 210 very low birth weight infants (VLBWIs), defined as either less than 32 weeks of gestational age (GA) or weighing less than 1500 g, were admitted to the Neonatal Intensive Care Unit (NICU) at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2020 and June 2023. Fourteen infants were excluded from the study as they did not survive beyond 1 month of life, and one was excluded due to a congenital anomaly. Consequently, the analysis included 195 VLBWIs. The Quality Improvement (QI) initiative began in January 2022, marking the division into two distinct epochs: the Pre-QI period, encompassing the years 2020 to 2021, and the Post-QI period, spanning from 2022 to 2023. The primary outcome measures included PICC insertion rates, duration, and feeding advancement or feeding-related complications. The hospital outcome measures were also compared between the two periods. A total of 195 VLBWI were included in the analysis. The birth weight was significantly lower in the pre-QI period, with an average of 1023 g compared to 1218 g (P < 0.001). Severe BPD ≥ moderate was significantly lower in the post-QI period (36.2% vs. 53.9%) (P < 0.001) along with shorter mechanical ventilation days (12 ± 29 vs. 22 ± 27) (P = 0.046). The PICC insertion rate was significantly decreased from 95.6% in pre-QI period compared to 55.2% in post-QI period (P < 0.001) along with a notable reduction in blood culture-proven sepsis (25.6% vs. 10.5%, P = 0.008). CRBSI rate was reduced from 1.3 to 1.1 per 1000 catheter days in the post-QI period. Moreover, the time required to achieve full enteral feeding of 100 mL/kg/day was significantly shorter in the post-QI (24 ± 23 vs. 33 ± 25) (P = 0.006). Multivariable logistic regression analysis for sepsis revealed that both birth weight and pre/post QI consistently demonstrated an association with lower sepsis rates in the Post-QI period. QI has the potential to reduce the burden of unnecessary interventions and blood culture proven sepsis rate along with CRBSI rate, thereby, optimizing the better care of very preterm babies., (© 2024. The Author(s).)

Background: This latest systematic review and meta-analysis aim to examine the effects of probiotic and synbiotic supplementation in critically ill patients., Methods: Relevant articles were retrieved from PubMed, Embase, the Cochrane Database, and the Web of Science. The primary output measure was the incident of ventilator-associated pneumonia, and the secondary outputs were diarrhea, Clostridium diffusion infection (CDI), incident of sepsis, incident of hospital acquired pneumonia, duration of mechanical exploitation, ICU mortality rate, length of ICU stay, in hospital mortality, and length of hospital stay. Data were pooled and expressed as Relative Risk(RR) and Standardized Mean Difference (SMD) with a 95 % confidence interval (CI)., Results: 33 studies were included in this systematic review and meta-analysis, with 4065 patients who received probiotics or synbiotics (treatment group) and 3821 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced incidence of ventilation-associated pneumonia (VAP) (RR = 0.80; 95 % CI: 0.67-0.96; p = 0.021, I 2  = 52.5 %) and sepsis (RR = 0.97; 95 % CI: 0.66-1.42; p = 0.032, I 2  = 54.4 %), As well as significantly increased duration of mechanical exploitation (SMD = -0.47; 95 % CI: -0.74-0.20, p = 0.012, I 2  = 63.4 %), ICU mobility (RR = 0.95; 95 % CI: 0.71-1.27; p = 0.004, I 2  = 62.8 %), length of ICU stay (SMD = -0.29; 95 % CI: -0.58-0.01; p = 0.000, I 2  = 82.3 %) and length of hospital stay (SMD = -0.33; 95 % CI: -0.57-0.08, p = 0.000, I 2  = 74.2 %) than the control group. There were no significant differences in diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality between the two groups., Conclusion: Our meta-analysis showed that probiotic and synbiotic supplements are beneficial for critically ill patients as they significantly reduce the incidence of ventilator associated pneumonia and sepsis, as well as the duration of mechanical exploitation, length of hospital stay, length of ICU stay, and ICU mortality. However, this intervention has minimal impact on diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality in critically ill patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiliang Li reports financial support was provided by Medical Scientific Research Foundation of Zhejiang Province. Youfen Fan reports financial support was provided by the Project of NINGBO Leading Medical&Health Discipline., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: The aim of this study was to compare modified 2-stage and 3-stage IPAA construction techniques to evaluate the effect of diverting loop ileostomy following completion proctectomy and IPAA for ulcerative colitis. In addition, our overall institutional experience was reviewed to describe long-term outcomes and changes in staging trends over time., Methods: Our institutional database was searched to identify all cases of IPAA for ulcerative colitis between 1981 and 2018. Patient, pouch and outcome characteristics were abstracted. Primary study outcomes were the incidence of primary pouch failure and pouch-related sepsis. Failure was evaluated by Kaplan-Meier estimates of survival over time. The adjusted effect of pouch stage was evaluated using multivariable Cox and logistic regression models. Exploratory analysis evaluated the effect of stage on failure in the pouch related sepsis subgroup., Results: A total of 2105 patients underwent primary IPAA over the study period. The 5, 10 and 20-year pouch survival probabilities were 95.2%, 92.7% and 86.6%. The incidence of pouch related sepsis was 12.3%. Adjusted analysis demonstrated no difference in pouch failure (HR = 0.64: 95% 0.39-1.07, p = 0.09) or post-operative sepsis (aOR = 0.79: 95% CI 0.53-1.17, p = 0.24) by stage of construction. Among patients experiencing pouch sepsis, there was no difference in Kaplan-Meier estimates of pouch survival by stage (p = 0.90)., Conclusions: Pouch related sepsis and IPAA failure did not differ between modified 2-stage and 3-stage construction techniques. Among the sub-group of patients experiencing pouch related sepsis, there was no difference in failure between groups. The results suggest diverting ileostomy may be safely avoided following delayed pouch reconstruction in appropriately selected patients., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objectives: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths., Search Strategy: PubMed, Scopus and Web of Science databases were searched in March 2023., Selection Criteria: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo., Data Collection and Analysis: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel-Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach., Main Results: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55-0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22-1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30-0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56-0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65-2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76-1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96-1.09; moderate certainty evidence)., Conclusions: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: The intestinal microflora has an essential role in providing a barrier against colonisation of pathogens, facilitating important metabolic functions, stimulating the development of the immune system, and maintaining intestinal motility. Probiotics are live microorganisms that can be administered to supplement the gut flora. Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be partly due to a disruption of the integrity of the gut and its intestinal microflora. There may be a role for probiotics in reducing the incidence of sepsis and improving intestinal motility, thus reducing morbidity and mortality and improving enteral feeding in neonates in the postoperative period., Objectives: To evaluate the efficacy and safety of administering probiotics after gastrointestinal surgery for the postoperative management of neonates born from 35 weeks of gestation., Search Methods: We searched CENTRAL, MEDLINE, Embase, and trial registries in August 2023. We checked reference lists of included studies and relevant systematic reviews for additional studies., Selection Criteria: We included randomised controlled trials (RCTs) that investigated the postoperative administration of oral probiotics versus placebo or no treatment in neonates born from 35 weeks of gestation who had one or more gastrointestinal surgical procedures. We applied no restrictions regarding the type or dosage of probiotics or the duration of treatment., Data Collection and Analysis: We used standard Cochrane methods, and we used GRADE to assess the certainty of evidence., Main Results: We identified one RCT that recruited 61 neonates with a gestational age of 35 weeks or more. All infants were admitted to a neonatal intensive care unit and had surgery for gastrointestinal pathologies. There may be little or no difference in proven sepsis (positive bacterial culture, local or systemic) between infants who receive probiotics compared with those who receive placebo (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.16 to 2.55; 61 infants; low-certainty evidence). Probiotics compared to placebo may have little or no effect on time to full enteral feeds (mean difference (MD) 0.63 days, 95% CI -4.02 to 5.28; 61 infants; low-certainty evidence). There were no reported deaths prior to discharge from hospital in either study arm. Two weeks after supplementation, the infants who received probiotics had a substantially higher relative abundance of non-pathogenic intestinal microflora (Bifidobacteriaceae) than those who received placebo (MD 38.22, 95% CI 28.40 to 48.04; 39 infants; low-certainty evidence)., Authors' Conclusions: This review provides low-certainty evidence from one small RCT that probiotics compared to placebo have little or no effect on the risk of proven sepsis (positive bacterial culture, local or systemic) or time to full-enteral feeds in neonates who have undergone gastrointestinal surgery. Probiotics may substantially increase the abundance of beneficial bacterial in the intestine of these neonates, but the clinical implications of this finding are unknown. There is a need for adequately powered RCTs to assess the role of probiotics in this population. We identified two ongoing studies. As neither reported the gestational age of prospective study participants, we are unsure if they will be eligible for inclusion in this review., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

In patients with central venous catheters (CVCs) in situ, the development of catheter-related bloodstream infections (CRBSIs) is often linked with increased morbidity and mortality. Sterile gauze or transparent polyurethane dressings are conventionally used as extraluminal barriers; however, antimicrobial chlorhexidine CVC dressings could potentially reduce infection risk. This short evidence-based review examined the literature comparing the effectiveness of chlorhexidine-based CVC dressings against non-chlorhexidine dressings in reducing CRBSI occurrence. Four systematic reviews with meta-analysis were reviewed, all of which reported a statistically significant reduction in CRBSI occurrence on using chlorhexidine-based dressings. Further research is needed to determine the cost-effectiveness of chlorhexidine-based CVC dressings and their effectiveness in reducing CRBSIs in different catheter types and entry sites because infection risk is not uniform., (© 2022 British Association of Critical Care Nurses.)

Background: Central-venous-line-associated bloodstream infection (CLABSI) is a significant cause of morbidity and mortality in preterm infants. As there is large variation in the reported effect of multi-modal preventive strategies, it could be relevant to propose new additional strategies., Aim: To assess the impact of a new perfusion system on CLABSI rate., Methods: A before-and-after study was performed in infants born at <32 weeks of gestation or with birth weight <1500 g who required a multi-perfusion system connected to a central venous line. In the first 12-month period ('before'), the pre-existing perfusion system (multiple stopcocks) was used. An intervention period then occurred with implementation of a new perfusion closed system, without change in 'bundles' related to various aspects of central line care. During the second 12-month period ('after'), the CLABSI rate was assessed and compared with the pre-intervention period., Findings: In total, 313 infants were included in this study (before: N=163; after: N=150), and 46% had birth weight <1000 g. The change in perfusion system resulted in a significant decrease in CLABSI rate from 11.3 to 2.2 per 1000 catheter-days (P<0.001). The period was independently associated with an 88% reduction in the risk of CLABSI after implementation of the new perfusion system [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.03-0.39; P<0.001]. The duration of central line use was also associated with CLABSIs (for each additional day: OR 1.05, 95% CI 1.02-1.07; P<0.001)., Conclusions: Implementation of the new perfusion system was feasible in a large neonatal unit, and reduced the CLABSI rate soon after implementation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is important to put evidence-based guidelines into practice in the prevention of central line-associated bloodstream infections in intensive care patients. In contrast to expensive and complex interventions, a care bundle that includes easy-to-implement and low-cost interventions improves clinical outcomes. The compliance of intensive care nurses with guidelines is of great importance in achieving these results. The Translating Evidence into Practice Model provides guidance in how to implement the necessary guidelines. This quasi-experimental study used a post-test control group design in nonequivalent groups and was conducted in the anesthesia intensive care unit of a tertiary-level training and research hospital. All patients who were hospitalized in the intensive care unit, who had a central line during the study, and who met the inclusion criteria were included in the sample. The care bundle comprised education, and protocols for hand hygiene and the aseptic technique, maximum sterile barrier precautions, central line insertion trolley, and management of nursing care. To analyze the data, the independent samples t-test, the Mann-Whitney U test, chi-square test, dependent samples t-test, rate ratio, and relative risk were used with 95% confidence intervals. The rate of central line-associated bloodstream infections was significantly lower in the intervention group (2.85/1000 central line days) than in the control group (3.35/1000 central line days) (P = 0.042). The number of accesses to the central line by the nurses decreased significantly in the intervention group compared to the control group (P < 0.001). The mean score for the nurses' evidence-based guideline post-education knowledge (70.80 ± 12.26) was significantly higher than that pre-education (48.20 ± 14.66) (P < 0.001). Compliance with the guideline recommendations in central line-related nursing interventions and in the central line insertion process was significantly better in the intervention group than in the control group in many interventions (P < 0.05). The mean score for the nurses' attitude towards evidence-based nursing increased significantly over time (59.87 ± 7.23 at the 0th month; 63.79 ± 7.24 at the 6th month) (P < 0.001). Nursing care given by implementing the central line care bundle with the Translating Evidence into Practice Model affected the measures. Thanks to the implementation of the care bundle, the rate of infections and the number of accesses to the central line decreased, while the critical care nurses' knowledge of evidence-based guidelines, compliance with the guideline recommendations in central line-related nursing interventions, and attitudes towards evidence-based nursing improved., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality. Akkermansia muciniphila (AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development., Design: Relative abundance of gut microbial AKK in septic patients was evaluated. Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) injection were employed to establish sepsis in mice. Non-targeted and targeted metabolomics analysis were used for metabolites analysis., Results: We first found that the relative abundance of gut microbial AKK in septic patients was significantly reduced compared with that in non-septic controls. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably reduced sepsis-induced mortality in sepsis models. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. Furthermore, RKH markedly reduced sepsis-induced inflammatory cell activation and proinflammatory factor overproduction. A mechanistic study revealed that RKH could directly bind to Toll-like receptor 4 (TLR4) and block TLR4 signal transduction in immune cells. Finally, we validated the preventive effects of RKH against sepsis-induced systemic inflammation and organ damage in a piglet model., Conclusion: We revealed that a novel tripeptide, RKH, derived from live AKK, may act as a novel endogenous antagonist for TLR4. RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Obesity is a major determinant of health outcomes and is on the increase in women worldwide. It predisposes to surgical site infection (SSI). Risk factors for the SSI include extremes of age, smoking, comorbidities such as hypertension and diabetes, inappropriate vertical abdominal and or uterine wall incisions, increased operating time, subcutaneous layer of 3 cm or more, and unnecessary use of subcutaneous drain. Most bacteria that cause SSIs are human commensals. Common organisms responsible for SSI include Staphylococcus aureus and coliforms such as Proteus mirabilis, and Escherichia coli. A surgeon's gloves post caesarean section in the obese has a preponderance of Firmicutes and Bacteroidetes, which increases SSI risk. The interaction of skin commensals and vaginal microbiome at the surgical incision site increases the risk of SSI in the obese compared to non-obese. Minimizing the risk of SSI involves modification of risk factors, timely treatment of SSI to prevent sepsis and compliance with the recommended care bundles., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)