Sepsis-related Morbidity Research Articles

Patient and community centered approaches to sepsis among birthing people

Sepsis is the second leading cause of maternal death in the U.S. For racial and ethnic minoritized birthing people, especially those who are Black and living in underserved communities, labor and postpartum are particularly vulnerable risk periods. To reduce sepsis-related morbidity and mortality and promote maternal health equity, community co-led, and co-designed interventions are urgently needed. In this commentary, we introduce the design and goals of our EnCoRe MoMS study as an exemplar for employing community based participatory research principals iteratively throughout the research process and integrated across all study aims. We also highlight our early lessons learned and recommendations for best practices. Our novel model and ongoing work have implications for scaling academic-community research partnerships for other causes of severe maternal morbidity and maternal health equity nationally.

ThP3.3 - Prophylactic Endoluminal Vacuum Therapy – towards an era of reducing leak related morbidity after elective oesophago-gastric resection

Abstract Aims Uncontrolled sepsis following leak from oesophago-gastric surgery is a devastating condition with increased morbidity & mortality affecting longer-term cancer-free survival in patients with cancer resections. We hypothesised that endoluminal vacuum therapy (EVT), previously used to treat leaks, could be used in prophylactic settings to provide source-control, prevent mediastinitis and minimise sepsis related morbidity from leaks. Methods An ad-hocEVT device was created using VACgranufoam (KCI)and a nasogastric-tube(16/18Fr), and placed intraluminally across the repair/anastomosis in select high-risk cases. Continuous negative pressure(75–125mmHg) was applied. Assessment of the repair-site/anastomosis was performed by radiology, endoscopy, clinical assessment or a combination following cessation of EVT. Results 27 patients had prophylactic EVT; M:F ratio was 3:1 and the median age was 68 years (range: 41-82years). 26surgeries were for cancer, while 1 was benign. The rationale for prophylactic EVT included patient related (10), technical factors (16) or both (1). The median duration of prophylactic EVT was 7 days (range: 4-14days). The median length-of-stay was 19.7 days (range: 6-96 days), the two longest admissions were unrelated to the anastomosis(prolonged chyle-leak, and long-term-sequelae of life-threatening bleed). One-patient developed a full-thickness microleak at endoscopic-evaluation, yet remained well with no systemic signs of sepsis, successfully managed with luminalEVT for a further 6days in a ward-based environment. Though prophylacticEVT did not prevent the leak, it significantly minimised the systemic hit that traditionally results from leak and associated mediastinal sepsis. Conclusions ProphylacticEVT is a useful adjunct for management of patients with a high risk for leak, though not a substitute for good surgical technique. There are no short-term complications, yet the additional morbidity, mortality and length-of-stay associated with a fully-fledged leak is avoided. Randomised-controlled-trials are required to further standardise selection criteria, assess potential patient benefit and longer-term impact on survivorship.

Diagnostic Accuracy of Clinical Sign Algorithms to Identify Sepsis in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

Accurate identification of possible sepsis in young infants is needed to effectively manage and reduce sepsis-related morbidity and mortality. Synthesize evidence on the diagnostic accuracy of clinical sign algorithms to identify young infants (aged 0-59 days) with suspected sepsis. MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. Studies reporting diagnostic accuracy measures of algorithms including infant clinical signs to identify young infants with suspected sepsis. We used Cochrane methods for study screening, data extraction, risk of bias assessment, and determining certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. We included 19 studies (12 Integrated Management of Childhood Illness [IMCI] and 7 non-IMCI studies). The current World Health Organization (WHO) 7-sign IMCI algorithm had a sensitivity of 79% (95% CI 77%-82%) and specificity of 77% (95% CI 76%-78%) for identifying sick infants aged 0-59 days requiring hospitalization/antibiotics (1 study, N = 8889). Any IMCI algorithm had a pooled sensitivity of 84% (95% CI 75%-90%) and specificity of 80% (95% CI 64%-90%) for identifying suspected sepsis (11 studies, N = 15523). When restricting the reference standard to laboratory-supported sepsis, any IMCI algorithm had a pooled sensitivity of 86% (95% CI 82%-90%) and lower specificity of 61% (95% CI 49%-72%) (6 studies, N = 14278). Heterogeneity of algorithms and reference standards limited the evidence. IMCI algorithms had acceptable sensitivity for identifying young infants with suspected sepsis. Specificity was lower using a reference standard of laboratory-supported sepsis diagnosis.

Evaluation of Vitamin (A) Deficiency among Critically Ill Children with Sepsis

Abstract Background Vitamin A is an immunomodulatory, and its deficiency may cause impaired immune function, which are found in sepsis. There is a biological rationale that vitamin A deficiency (VAD) may be a contributing factor related to poor clinical outcomes in patients with sepsis. Aim of the Work to assess the prevalence of vitamin A deficiency in critically ill children with sepsis and its association with clinical outcomes. Patients and Methods This cross-sectional study included 40 critically ill children with sepsis who were admitted to the paediatric intensive care unit. The control group consisted of 40 age- and sex-matched approximate-health children from outpatient clinic. For the measurement of serum vitamin A status, blood samples were taken from all patients within the first 24 hours of admission. The vitamin A status of the sepsis and control groups were compared. Univariate and multivariate approaches were used to assess the link between vitamin A deficiency and sepsis. Results The study enrolled 40 children with sepsis and 40 matched healthy children so there was no statistically significant difference between controls and patients among age and sex, with median age 4 (2 – 12) months for both groups with male predominance (60.0%). Regarding body measures there was a high statistically significant lower values among patients group than controls group for z score of weight, height/length, body mass index (BMI) and mid arm circumference (MAC) of the studied subjects, that indicated increased malnutrition prevalence among septic children than control group. In the present study, by comparing VAD between patients and controls, there was high statistically significant difference as all septic patients (100%) had VAD and the VAD among healthy control was found in 30% of them. We also found that patients with septic shock, patients who were nothing per os (NPO), patients on ventilators and died patients were more deficient in vitamin A level than other patients compared with them (high statistically significant difference), illustrated that VAD may be had a role in sepsis related morbidity and mortality. There was a positive correlation between vitamin A and BMI z score and MAC while there was a negative correlation with prism 3 and prism 4.ROC curve for assessment of vitamin A as a predictor of sepsis, found that at cut off value ≤9 μg/dl, the Sensitivity, Specificity, positive predictive value (PPV) and negative predictive value (NPV) were 100% for each. Conclusion low level of vitamin A, lower than or equal to 9 μg/dl was associated with sepsis, septic shock, and higher PRISM score. Vitamin A deficiency may be a marker of morbidity and mortality in critically ill children with sepsis.

One-Hour Bundle Protocols for Surgical Sepsis and Septic Shock in Surgical Intensive Care Unit: Clinical Outcome Aspects in the Thai Context.

Surgical sepsis is a syndrome occurring during the perioperative period with a high mortality rate. Since the one-hour bundle protocol was recommended to decrease sepsis-related morbidity and mortality in clinical practice, the protocol has been applied to surgical patients with sepsis and septic shock. However, clinical outcomes in these surgical patients remain unknown. Thus, this study aimed to compare survival outcomes in patients before and after the implementation of one-hour bundle care in clinical practice. In thisprospective cohort study, 401 surgical patients with sepsis were divided into two groups, with 195 patients undergoing the one-hour bundle from December 25, 2021, to March 31, 2024, and 206 patients undergoing usual care from January 1, 2018, to December 24, 2021, before the one-hour bundle protocol was implemented by the Surviving Sepsis Campaign (SSC). Demographic data, treatment processes, and clinical outcomes were recorded. After the one-hour bundle protocol was applied in surgical practice, the median survival time was significantly increased in surgical patients who underwent one-hour bundle care (95% confidence interval (CI): 12.32-19.68) (p= 0.016). Factors influencing the increase in the mortality rate were delays in fluid resuscitation of >2 hours, vasopressor initiation of >2 hours, and empirical antibiotics of >5 hours (p= 0.017, 0.028, and 0.008, respectively). One-hour bundle care for surgical patients with sepsis resulted in an increased median survival time. Delays in fluid resuscitation (>2 hours), vasopressor initiation (>2 hours), and empirical antibiotics (>5 hours) were factors associated with mortality.

Antibiogram of Bacteria Isolated from Bloodstream Infection-Suspected Patients at the University of Gondar Comprehensive Specialized Hospital in Northwest Ethiopia: A Retrospective Study.

Bacterial bloodstream infections (BSIs) are the leading cause of sepsis-related morbidity and mortality worldwide. The emergence and spread of antimicrobial resistance (AMR) in bacteria is also a growing global concern. As a result, data on bacterial profile and their antibiogram are essential for strategies to contain drug resistance, improve the quality of patient care, and strengthen health systems. Retrospective data from bacteriological results of blood samples of BSI-suspected patients from 2018 to 2021 were collected using a data collection sheet. Standard bacteriological techniques were followed during sample collection, culture preparation, bacterial identification, and antibiotic susceptibility testing (AST). We used Epi Info version 7 to enter and clean the data and then exported it to SPSS version 26 for analysis. Logistic regression models were used to measure the association between variables. A p value <0.05 with a 95% confidence interval was considered as statistically significant. Of the total 2,795 blood culture records, 455 (16.3%) were culture positive for bacteria, with Klebsiella pneumoniae (26%) and Staphylococcus aureus (24.6%) being the leading isolates. The isolates were highly resistant to common antibiotics, with more than 80% of them being resistant to ceftriaxone and penicillin. Moreover, about 43% of isolates were multidrug resistant (MDR), with Klebsiella pneumoniae (65.5%), Acinetobacter species (56.7%), and Citrobacter species (53.8%) being the most common MDR isolates. Age and diagnosis year were significantly associated with the presence of bacterial BSIs (p value <0.05). Bacterial BSI and AMR were growing concerns in the study area. Bacteremia was more common in children under the age of five, and it decreased as the patient's age increased. The alarming rate of AMR, such as MDR blood isolates, calls for periodic and continuous monitoring of antibiotic usage in the study area.

Risk factors and etiology of early-onset neonatal sepsis in Northeastern part of India: Case-control study.

Sepsis, the second most common cause of neonatal mortality, causes more than one million deaths annually. India has the highest incidence of clinical sepsis (17000/100000 live birth). This study aimed to determine the risk factors and organisms of early-onset neonatal sepsis (EONS) in a tertiary care hospital in Northeast India. It was a case-control study conducted in the neonatal unit of MGM Medical College, Kishanganj, Bihar, from January 2022 to April 2023. All neonates admitted to the neonatal intensive care unit (NICU) within 72 hours of life constituted the study population. Neonates diagnosed as EONS by clinical and laboratory parameters were considered as cases and those not diagnosed for EONS as controls. Maternal and newborn information and laboratory parameters were collected and analyzed. For risk factor identification, the bivariate logistic regression was used. An equal number of cases (78) and control (78) were enrolled in the study. Maternal age >30 years (adjusted odds ratio [aOR] = 3.017, confidence interval [CI]: 1.238 to 7.352; P < 0.015), maternal urinary tract infection (UTI) in the third trimester (aOR = 5.435, CI: 2.647 to 11.158; P < 0.0001), and premature rupture of membranes (PROM) (aOR = 2.918, CI: 4.61 to 33.73, P < 0.004) were significant predictors of EONS. Pseudomonas (41.02%), Klebsiella (16.66%), and coagulase-negative Staphylococcus aureus (20.51%) were commonly isolated organisms, which were highly resistant to cephalosporin, meropenem, aminoglycosides, and quinolones. Proper and adequate antenatal screening for diagnosis and treatment of maternal infection and high-risk pregnancies for perinatal management of newborn is recommended to prevent neonatal sepsis-related morbidity and mortality. Rational use of antibiotics may minimize the hazard of antibiotic resistance.

Serotonin Signaling and the Hyperpermeable Endothelial Barrier in Sepsis: Clues to a Molecular Mechanism.

Sepsis is characterized by a severe systemic inflammatory response caused by hyperpermeability of the endothelial barrier resulting microvascular leakage, which is a leading factor to multiorgan failure. In sepsis, the hyperpermeable endothelial cells contribute to the activation of platelets, which release numerous mediators that affect coagulation, inflammatory response and are believed to directly or indirectly affect the integrity of the endothelial barrier. One such mediator is serotonin (5-hydroxytryptamine, 5-HT), a signaling molecule which mediates a number of cellular functions including regulation of cytoskeletal dynamics associated with barrier function of endothelial cells. The actions of 5-HT are mediated by different types of receptors and terminated via an uptake mechanism of a 5-HT transporter (SERT) on the platelet and endothelial cell. Earlier studies revealed unexpected discoveries concerning the impact of 5-HT signaling on the permeability of the endothelial barrier. These findings have been supported by the clinical reports on the anti-inflammatory property of 5-HT reuptake inhibitor, SSRIs in treating sepsis-related morbidity and mortality. This review focuses on a wide-range of literature to pinpoint cellular and molecular mechanisms that mediate 5-HT-induced microvascular injury in sepsis pathogenesis.

Most patients with an increased risk for sepsis-related morbidity or death do not recognize sepsis as a medical emergency: results of a survey study using case vignettes

BackgroundSepsis is a medical emergency with potentially life-threatening consequences. Patients play a crucial role in preventing and recognizing sepsis at an early stage. The understanding of risk groups’ sepsis knowledge and their ability to use this knowledge to recognize sepsis as an emergency is incomplete.MethodsWe conducted a cross-sectional survey in Germany and included a sample of 740 persons stratified by age (< 60 years, ≥ 60 years), specific chronic diseases (e.g. diabetes, chronic diseases, cancer), and region (Berlin/Brandenburg vs. other federal states of Germany). Standardized questionnaires were administered by a market research institute through online, telephone, or face-to-face methods. We assessed sepsis knowledge through a series of questions and the ability to recognize sepsis as an emergency through five case vignettes. To identify predictors of sepsis knowledge and the ability to recognize sepsis as a medical emergency, we conducted multiple linear regressions.ResultsOf the 36 items on sepsis knowledge, participants answered less than 50 per cent correctly (mean 44.1%; standard deviation (SD) 20.1). Most patients knew that sepsis is a defensive host response to infection (75.9%), but only 30.8% knew that vaccination can prevent infections that lead to sepsis. Across the five vignettes, participants identified sepsis as an emergency in only 1.33 of all cases on average (SD = 1.27). Sepsis knowledge was higher among participants who were older, female, and more highly educated and who reported more extensive health information seeking behaviour. The ability to recognize sepsis as an emergency was higher among younger participants, participants without chronic diseases, and participants with higher health literacy, but it was not significantly associated with sepsis knowledge.ConclusionsRisk groups showed low levels of knowledge regarding the preventive importance of vaccination and a low ability to recognize sepsis as a medical emergency. Higher levels of sepsis knowledge alone were not sufficient to improve the ability to identify sepsis as a medical emergency. It is crucial to develop effective educational strategies—especially for persons with lower education levels and infrequent health information seeking behaviour—that not only transfer but also facilitate the choice of appropriate actions, such as seeking timely emergency care.Trial registration: DRKS00024561. Registered 9 March 2021.

Comparative efficacy of micro-erythrocyte sedimentation rate (m-ESR) and C-reactive protein (CRP) as a neonatal septic screening marker—a single-center, retrospective observational study

BackgroundNeonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in neonatal period. Most of neonatal sepsis-related morbidity and mortality can be prevented by early diagnosis and treatment with appropriate antimicrobial agents. Micro-erythrocyte sedimentation rate (m-ESR) is a simple, inexpensive, and rapid screening test for neonatal sepsis that can be done even in resource limited setups.ObjectivesTo compare the efficacy of m-ESR with C-reactive protein (CRP) as a screening tool in neonatal sepsis.MethodologyA retrospective chart-based analysis was done in division of neonatology, of our tertiary care hospital over a period of 21 months. A total of 202 suspected cases of neonatal sepsis with documented CRP and micro-ESR values were included. We evaluated the role of micro-ESR as a screening tool in neonatal sepsis in comparison with CRP. The validity and reliability of micro-ESR in comparison to CRP were estimated and its sensitivity, specificity, positive, and negative predictive value to diagnose sepsis were calculated.ResultsThere was a significant correlation between micro-ESR and CRP with a moderate degree of agreement, especially in ‘late onset sepsis’ group. The overall sensitivity, specificity, positive predictive value and negative predictive value of micro-ESR were 67%, 84%, 58%, and 89% respectively.ConclusionMicro-ESR is a simple, inexpensive test comparable to CRP in screening for neonatal sepsis.

Thymol regulates the Endothelin-1 at gene expression and protein synthesis levels in septic rats

Sepsis is a serious systemic inflammatory response to infections. In this study, effects of thymol treatments on sepsis response were investigated. A total of 24 rats were randomly divided into 3 different treatment groups, namely as Control, Sepsis and Thymol. A sepsis model was created with a cecal ligation and perforation (CLP) in the sepsis group. For the treatment group, 100 mg/kg dose of thymol was administered via oral gavage and sepsis was established with a CLP after 1 h. All rats were sacrificed at 12 h post-opia. Blood and tissue samples were taken. ALT, AST, urea, creatinine and LDH were evaluated to assess the sepsis response in separated sera. Gene expression analysis was conducted for ET-1, TNF-α, IL-1 in lung, kidney and liver tissue samples. ET-1 and thymol interactions were determined by molecular docking studies. The ET-1, SOD, GSH-Px and MDA levels were determined by ELISA method. Genetic, biochemical and histopathological results were evaluated statistically. The pro-inflammatory cytokines and ET-1 gene expression revealed a significant decrease in the treatment groups, while there was an increase in septic groups. SOD, GSH-Px and MDA levels of rat tissues were significantly different in the thymol groups as compared to the sepsis groups (p < 0.05). Likewise, ET-1 levels were significantly reduced in the thymol groups. In terms of serum parameters, present findings were consistent with the literature. It was concluded based on present findings that thymol therapy may reduce sepsis-related morbidity, which would be beneficial in the early phase of the sepsis.

Plants' bioactive secondary metabolites in the management of sepsis: Recent findings on their mechanism of action.

Sepsis is a severe inflammatory response to systemic infection and is a threatening cause of death in intensive care units. In recent years, a number of studies have been conducted on the protective effect of natural products against sepsis-induced organ injury. However, a comprehensive review of these studies indicating the mechanisms of action of the bioactive compounds is still lacking. In this context, this review aimed to provide an updated analysis of the mechanism of action of plants' secondary metabolites in the management of sepsis. Scopus, Science Direct, Google Scholar, and PubMed were searched from inception to July 2022. A variety of secondary metabolites were found to be effective in sepsis management including allicin, aloin, cepharanthine, chrysin, curcumin, cyanidin, gallic acid, gingerol, ginsenoside, glycyrrhizin, hesperidin, kaempferol, narciclasine, naringenin, naringin, piperine, quercetin, resveratrol, rosmarinic acid, shogaol, silymarin, sulforaphane, thymoquinone, umbelliferone, and zingerone. The protective effects exerted by these compounds can be ascribed to their antioxidant properties as well as induction of endogenous antioxidant mechanisms, and also via the downregulation of inflammatory response and reduction of biochemical and inflammatory markers of sepsis. These findings suggest that these secondary metabolites could be of potential therapeutic value in the management of sepsis, but human studies must be performed to provide strength to their potential clinical relevance in sepsis-related morbidity and mortality reduction.

OGC P37 Towards an era of eliminating leak related morbidity from major oesophago-gastric surgery

Abstract Background A leak following oesophago-gastric surgery remains a life-threatening complication associated with a long intensive care stay and high mortality and morbidity. We hypothesised that Endoluminal Vacuum Therapy (EVT) could be used prophylactically to provide source control, prevent mediastinitis and minimise sepsis related morbidity if breakdown of an oesophageal or gastric anastomosis or repair occurred. In the first instance, this could be a particularly attractive adjunct in cases where technical and/or patient factors deem an anastomosis or repair as high risk. Methods We collected data prospectively from all patients where a prophylactic EVT device was placed during elective oesophago-gastric surgery. Primary outcome measures included length of stay (LOS) and post-operative leak rate. Prophylactic EVT was provided using an ad-hoc EVT device constructed by suturing a piece of V.A.C granufoam (KCI) to the end of an 18Fr NG tube and positioning this intraluminally across the anastomosis or area of repair at the time of surgery using endoscopic guidance. Continuous negative pressure of between 75 and 125mmHg was applied. Following removal of the EVT device, assessment of the integrity of the anastomosis or repair was made using one, or a combination of endoscopic assessment, CT with oral contrast, and clinical assessment. Results Prophylactic EVT was utilised in 9 patients; M:F ratio=7:2, median age 72 years (range 50–80). 8 patients had ASA 3, and 1 had ASA 2. The index surgery was resection of an epithelial cancer in 7 patients (3 partial/total gastrectomies, 4 oesophagectomies), resection of a gastric GIST in 1 patient, and a Hellers myotomy in 1 patient. All anastomosis/repairs were deemed high risk due to technical(n=3), patient(n=4) or combined (n=2) factors. Prophylactic EVT was placed for a median of 6 days (range 4–10). The integrity of the anastomosis/repair was assessed using both CT and gastroscopy (n=3), CT alone (n=3), gastroscopy alone (n=2), and clinical grounds (n=1). One patient was found to have a full thickness oesophageal defect at their first endoscopic assessment. This was managed with a further period of intraluminal EVT until the oesophageal defect healed. The patient remained clinically well throughout and was managed entirely with ward-based care. The median LOS was 11 days (range 7–96). The two longest stays were secondary to a prolonged chyle leak and longer term sequelae of a life threatening on-table bleed. In all cases the site of repair remained healthy with no evidence of early stricturing. Conclusions Prophylactic EVT therapy was safe and did not result in any short-term adverse events in this small cohort of patients. Although it may not prevent breakdown at the site of oesophageal anastomosis/repair and is not an alternative to sound surgical technique, the use of prophylactic EVT in high risk anastomosis could be beneficial in preventing life threatening sepsis and associated systemic effects resulting from inadequate source control. Current studies are under way to look at longer term outcomes in the form of prospective cohort studies and randomised controlled trials. This provides the oesophago-gastric community the unique opportunity to collectively eliminate life threatening leak related morbidity and mortality for once and for all.

Prompt Identification of Sepsis on Hospital Floors: Are Healthcare Professionals Ready for the Implementation of the Hour-1 Bundle?

Early intervention in sepsis management with recognized therapeutic targets may be effective in lowering sepsis-related morbidity and mortality, although this necessitates timely identification of sepsis by healthcare professionals. The present study aimed to assess knowledge levels, attitudes, and agreement among physicians regarding the Surviving Sepsis Campaign (SSC) guidelines (more specifically, the Hour-1 bundle). A quantitative, descriptive, cross-sectional study was conducted among physicians working in different clinical settings in Karachi, Pakistan, using a self-administered questionnaire. The mean cumulative knowledge score of the respondents towards SSC was 6.8 ± 2.1 (out of 10), where a total of n = 127 respondents (51.62%) had a strong understanding of the SSC guidelines, compared to n = 78 (31.7%) and n = 41 (16.7%) respondents with fair and inadequate knowledge, respectively. The majorly known bundle elements by the respondents were to administer broad-spectrum antibiotics (89.8%, n = 221), the need for taking blood cultures before administering antibiotics (87.8%, n = 216), and measurement of blood lactate levels (75.6%, n = 186). Experienced physicians were more likely to use norepinephrine as the first-choice vasopressor (p < 0.001). Female respondents were more likely to consider the duration of antibiotic therapy to be determined according to the site of infection, the microbiological etiology, the patient’s response to treatment, and the likelihood of achieving adequate source control (p = 0.001). The current study concluded that respondents had an optimistic approach and frequently practice in accordance with the SSC guidelines, while some respondents were not up to date with the most recent guidelines. There is a need for further interventions and continuous medical education to encourage physicians towards appropriate use of the recommended guiding principles for improving treatment outcomes in sepsis patients.

406EMF Early Fluid Delivery by Emergency Medical Services for Sepsis Using a Novel Rapid Infusion Device

406EMF Early Fluid Delivery by Emergency Medical Services for Sepsis Using a Novel Rapid Infusion Device

Sex differences associate with late microbiome alterations after murine surgical sepsis.

Sepsis-induced gut microbiome alterations contribute to sepsis-related morbidity and mortality. Given evidence for improved postsepsis outcomes in females compared with males, we hypothesized that female mice maintain microbiota resilience versus males. Mixed-sex C57BL/6 mice underwent cecal ligation and puncture (CLP) with antibiotics, saline resuscitation, and daily chronic stress and were compared with naive (nonsepsis/no antibiotics) controls. For this work, the results of young (3-5 months) and old (18-22 months) adult mice were analyzed by sex, independent and dependent of age. Mice were sacrificed at days 7 and 14, and 16S rRNA gene sequencing was performed on fecal bacterial DNA. α and β diversity were determined by Shannon index and Bray-Curtis with principal coordinate analysis, respectively. False discovery rate (FDR) correction was implemented to account for potential housing effect. In control mice, there was no difference in α or β diversity between male and female mice (FDR, 0.76 and 0.99, respectively). However, male mice that underwent CLP with daily chronic stress had a decrease in microbiota α diversity at 7 days post-CLP (Shannon FDR, 0.005), which was sustained at 14 days post-CLP (Shannon FDR, 0.001), compared with baseline. In addition, male mice maintained differences in β diversity even at day 14 compared with controls (FDR, <0.0001). In contrast, female mice had a decreased microbiota α diversity (Shannon FDR, 0.03) and β diversity (FDR, 0.02) 7 days post-CLP but recovered their α and β diversity by post-CLP day 14 (Shannon FDR, 0.5, and FDR, 0.02, respectively). Further analysis of females revealed that only young female mice were not different (β diversity) post-CLP day 14 to controls. Although sepsis-induced perturbations of the intestinal microbiota occur initially in both male and female C57BL/6 mice, females demonstrate different microbiota by day 14. This may be seen primarily in younger females. This difference in recovery may play a role in outcome differences between sexes after sepsis.

Incidence, morbidity, and associated factors for sepsis in women hospitalized for delivery: a nationwide retrospective observational population-based study in Canada.

PurposeThe objective of this research was to examine the epidemiology of maternal sepsis in Canada.MethodsWe conducted a population-based retrospective cohort study of women (≥ 20 weeks gestation) hospitalized for delivery in all Canadian hospitals (excluding Quebec) between 1 April 2004 and 31 March 2017. Data were obtained from the national Canadian Institute for Health Information database and sepsis cases were identified via International Classification of Diseases, Tenth Revision, Canada (ICD-10-CA) codes. Our primary outcome was the number of hospitalizations for delivery associated with maternal sepsis. We further explored associations between patient characteristics, obstetric procedures/conditions, medical conditions, and maternal sepsis. Associations were presented using odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThere were 4,183 cases of sepsis in 3,653,783 hospitalizations for delivery during the study period, with an incidence of 114 (95% CI, 111 to 118) per 100,000 hospitalizations and a mortality rate of 0.5%. Annual sepsis rates per 100,000 hospitalizations ranged from a high of 160 (95% CI, 146 to 177) in 2004 to 94 (95% CI, 83 to 106) in 2011. Highest regional rates were observed in the Territories (224 per 100,000). Severe sepsis was seen in 14% (n = 568) of all patients with sepsis, which was one or more of septic shock (15%; n = 85), organ failure (61%; n = 345), intensive care unit admission (78%; n = 443), or mortality (3%; n = 19). Multivariable models showed that postpartum hemorrhage (OR, 2.9; 95% CI, 2.7 to 3.2), Cesarean delivery (OR, 3.2; 95% CI, 3.0 to 3.5), anemia (OR, 3.9; 95% CI, 3.5 to 4.3), hysterectomy (OR, 4.9; 95% CI, 3.6 to 6.6), chorioamnionitis (OR, 7.6; 95% CI, 6.9 to 8.3), as well as cardiorespiratory, renal and liver conditions were associated with maternal sepsis.ConclusionMaternal sepsis rates have been decreasing in Canada but remain higher than those in the UK and USA. Our study explored associations with maternal sepsis and shows that one in seven women with sepsis develop severe sepsis-related morbidity, which warrants risk stratification and health policy changes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12630-021-02158-0.

Delta Neutrophil Index as a Diagnostic Marker of Neonatal Sepsis

Abstract Objective Sepsis diagnosis is challenging due to nonspecific symptomatology in newborns. Timely diagnosis is essential for reducing sepsis-related morbidity and mortality. This study was performed to determine the diagnostic value of the delta neutrophil index (DNI) for detection of neonatal sepsis and to compare its efficacy with other conventional markers. Methods This study was conducted at a tertiary hospital in newborns with confirmed sepsis (n = 59), suspected sepsis (n = 46), and in age- and weight-matched controls (n = 49). DNI, white blood cell count, C-reactive protein (CRP) level, and platelet measurements were determined, and blood cultures were performed at the onset of symptoms. Results The mean DNI was significantly higher in confirmed and clinical sepsis groups compared with the control group. (6.9 ± 9.3, 1.9 ± 2.1, and 0.4 ± 0.5, respectively, p &lt; 0.001). ROC curve analysis also showed that the combination of DNI and CRP had the highest sensitivity (86%), specificity (100%), and positive predictive value (100%) for predicting neonatal sepsis. DNI values were significantly higher in nonsurvivors (p &lt; 0.05). Conclusion DNI could be used as a reliable diagnostic marker for neonatal sepsis, and high DNI could predict sepsis development and unfavorable outcomes. The diagnostic capability of DNI may be increased by assessing CRP measurements simultaneously.

Prophylactic Therapy with Human Amniotic Fluid Stem Cells Improves Long-Term Cognitive Impairment in Rat Neonatal Sepsis Survivors.

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.

Risk factors and etiology of neonatal sepsis after hospital delivery: A case-control study in a tertiary care hospital of Rajshahi, Bangladesh.

Sepsis is one of the major causes of neonatal death worldwide as well as in Bangladesh. The objective of the present study was to identify the risk factors and causative organisms of neonatal sepsis after delivery in a tertiary care hospital, Bangladesh. This was a case-control study conducted in the neonatal ward of Rajshahi Medical College Hospital (RMCH), a 1000-bed tertiary hospital situated in Rajshahi, Bangladesh. Neonates diagnosed as neonatal sepsis by clinical and laboratory parameters were included as cases in this study. Admitted neonates unsuspected or undiagnosed for sepsis were considered as controls. Maternal and neonatal information and their laboratory reports were collected and analyzed. Both bivariate and multiple logistic regression models were used to identify the risk factors of neonatal sepsis. A total of 91 cases and 193 controls were included in the study. Maternal history of urinary tract infection (UTI) during the third trimester of pregnancy (aOR 2.75, 95% CI: 1.04-7.23, p <0.05), premature birth (aOR 2.77, 95% CI: 1.08-7.13, p <0.05) and APGAR score <7 at five minutes (aOR 2.58, 95% CI: 1.04-6.39, p <0.05) were associated with onset of neonatal sepsis in multiple logistic regression model. All these factors were also associated with developing early-onset neonatal sepsis, while maternal UTI and male sex of neonates were associated with developing late-onset neonatal sepsis. Escherichia coli (40.7%), Staphylococcus aureus (27.5%), and Klebsiella pneumoniae (18.7%) were the commonly isolated organisms causing neonatal sepsis. All these organisms were highly resistant to common antibiotics like amoxicillin, cephalosporins, aminoglycosides and quinolones. Carbapenemase group of drugs along with amikacin, nitrofurantoin and linezolid were the most sensitive drugs. Strengthening the existing facility for antenatal screening for early diagnosis and treatment of maternal infection during pregnancy as well as identifying high-risk pregnancy for adequate perinatal management is necessary to prevent neonatal sepsis-related morbidity and mortality. Rational use of antibiotics according to local epidemiology and culture and sensitivity reports may minimize the increasing hazards of antibiotic resistance.