Reducing the burden of preventable deaths from sepsis in Canada: A need for a national sepsis action plan.

Sepsis is a global health threat with significant morbidity and mortality. Despite clinical practice guidelines and developed health systems, sepsis is often unrecognized or misdiagnosed, leading to preventable harm. In Canada, sepsis is responsible for 1 in 20 deaths and is a significant driver of health system costs. Despite being a signatory to the World Health Organization's Resolution WHA 70.7, adopted in 2017, Canada has not lived up to its commitment. Many existing sepsis policies were developed in response to a specific tragedy, and there is no national sepsis action plan. In this article, we describe the burden of sepsis, provide examples of existing, context-specific, reactionary sepsis policies, and urge a coordinated, proactive Canadian sepsis action plan to reduce the burden of sepsis.

DIFFERENTIAL SIGNALING EFFECTS OF ESCHERICHIA COLI AND STAPHYLOCOCCUS AUREUS IN HUMAN WHOLE BLOOD INDICATE DISTINCT REGULATION OF THE NRF2 PATHWAY.

ABSTRACT: Escherichia coli and Staphylococcus aureus are two of the most common bacterial species responsible for sepsis. While it is observed that they have disparate clinical phenotypes, the signaling differences elicited by each bacteria that drive this variance remain unclear. Therefore, we used human whole blood exposed to heat-killed E. coli or S. aureus and measured the transcriptomic signatures. Relative to unstimulated control blood, heat-killed bacteria exposure led to significant dysregulation (upregulated and downregulated) of >5,000 genes for each experimental condition, with a slight increase in gene alterations by S. aureus. While there was significant overlap regarding proinflammatory pathways, Gene Ontology overrepresentation analysis of the most altered genes suggested biological processes like macrophage differentiation and ubiquinone biosynthesis were more unique to heat-killed S. aureus, compared with heat-killed E. coli exposure. Using Ingenuity Pathway Analysis, it was demonstrated that nuclear factor erythroid 2-related factor 2 signaling, a main transcription factor in antioxidant responses, was predominately upregulated in S. aureus exposed blood relative to E. coli. Furthermore, the use of pharmacologics that preferentially targeted the nuclear factor erythroid 2-related factor 2 pathway led to differential cytokine profiles depending on the type of bacterial exposure. These findings reveal significant inflammatory dysregulation between E. coli and S. aureus and provide insight into the targeting of unique pathways to curb bacteria-specific responses.

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death.

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

The prevalence of acute kidney injury in patients with community-acquired pneumonia who required mechanical ventilation.

BACKGROUND: Community-acquired pneumonia (CAP) is a common reason for intensive care unit (ICU) admission and sepsis. Acute kidney injury (AKI) is a frequent complication of community-acquired pneumonia and is associated with increased short- and long-term morbidity and mortality and healthcare costs. OBJECTIVE: Describe the prevalence of AKI in patients with CAP requiring mechanical ventilation and evaluate its association with inhospital mortality. DESIGN: Retrospective cohort. SETTING: Intensive care unit. PATIENTS AND METHODS: We included patients with CAP on mechanical ventilation. Patients were categorized according to the development of AKI in the first 24 hours of ICU admission using the Kidney Disease Improving Global Outcomes (KDIGO) classification from no AKI, stage 1 AKI, stage 2 AKI, and stage 3 AKI. MAIN OUTCOME MEASURES: The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, hospital and ICU length of stay, ventilation duration, tracheostomy, and renal replacement therapy requirement. RESULTS: Of 1536 patients included in the study, 829 patients (54%) had no AKI while 707 (46%) developed AKI. In-hospital mortality was 288/829 (34.8%) for patients with no AKI, 43/111 (38.7%) for stage 1 AKI, 86/216 (40%) for stage 2 AKI, and 196/380 (51.7%) for stage 3 AKI (P<.0001). Multivariate analysis revealed that stages 1, 2, or 3 AKI compared to no AKI were not independently associated with in-hospital mortality. Older age, vasopressor use; decreased Glasgow coma scale, PaO2/Fio2 ratio and platelet count, increased bilirubin, lactic acid and INR were associated with increased mortality while female sex was associated with reduced mortality. CONCLUSION: Among mechanically ventilated patients with CAP, AKI was common and was associated with higher crude mortality. The higher mortality could not be attributed alone to AKI, but rather appeared to be related to multi-organ dysfunction. LIMITATIONS: Single-center retrospective study with no data on baseline serum creatinine and the use of estimated baseline creatinine distributions based on the MDRD (Modification of Diet in Renal Disease)equation which may lead to an overestimation of AKI. Second, we did not have data on the microbiology of pneumonia, appropriateness of antibiotic therapy or the administration of other medications that have been demonstrated to be associated with AKI.

Decompression sickness followed by diabetic ketoacidosis and sepsis shock: an unusual case report.

Decompression sickness (DCS) is caused by abrupt changes in extracorporeal pressure with varying severity. Symptoms range from mild musculoskeletal pain to severe organ dysfunction and death, especially among patients with chronic underlying disease. Here, we report an unusual case of a 49-year-old man who experienced DCS after a dive to a depth of 38 meters. The patient's symptoms progressed, starting with mild physical discomfort that progressed to disturbance of consciousness on the second morning. During hospitalization, we identified that in addition to DCS, he had also developed diabetic ketoacidosis, septic shock, and rhabdomyolysis. After carefully balancing the benefits and risks, we decided to provide supportive treatment to sustain vital signs, including ventilation support, sugar-reducing therapy, fluid replacement, and anti-infection medications. We then administered delayed hyperbaric oxygen (HBO2) when his condition was stable. Ultimately, the patient recovered without any sequelae. This is the first case report of a diver suffering from DCS followed by diabetic ketoacidosis and septic shock. We have learned that when DCS and other critical illnesses are highly suspected, it is essential to assess the condition comprehensively and focus on the principal contradiction.

Flap Closure in Neonatal Neural Tube Defects: Challenges in Flap Design and Lessons Learnt.

Background: Management of neural tube defects (NTDs) is challenging and the outcome is demanding. Aims: To analyze the outcomes in operated cases of NTDs closed using various types of flaps. Materials and Methods: The data between June 2017 and May 2023 were analyzed. The mode of presentation, timing of intervention, type of flap, neurological status after closure, status of the wound, presence of hydrocephalous, flap blackening, flap necrosis, features of sepsis, and the outcome were recorded and analyzed. Covered NTD; closure done using primary closure or 'Z' Plasty (everywhere); incomplete data; lost to follow-up; and not giving consent were excluded from the study. Results: Out of 92 cases, 35 were operated using the rhomboid flap, 33 using dufourmentel modification of limberg flap, and 24 using keystone island flap. The mean age at presentation was 4 days (range: 0-28 days). The mean duration of surgery after presentation was 2 days (range: 1-3 days). Mean operating time was 1.15 h (range: 0.45-3.15 h). A ventriculoperitoneal shunt was required in 62 cases at various stages. The preoperative and the postoperative power were nearly the same in all. Wound infection was seen in 2, 3, and 1 cases in each group. Blackening of the flap was seen in 3, 2, and 1 cases in three groups. Cerebrospinal fluid (CSF) leak was seen in 2, 2, and 0 cases. Wound dehiscence was present in one case in each group and sepsis was present in 2, 3, and 2, respectively. Conclusion: The management of open NTD requires adequate planning. CSF shunting and flap closure are often required.

Cytomegalovirus infection in non-immunocompromised critically ill patients: A management perspective.

Critically ill patients are a vulnerable group at high risk of developing secondary infections. High disease severity, prolonged intensive care unit (ICU) stay, sepsis, and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections, including cytomegalovirus (CMV). CMV seroconversion has been reported in up to 33% of ICU patients, but its impact on patient outcomes remains a matter of debate. Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/ acquired immuno deficiency syndrome, the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous. Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement. Hence, a better understanding of the symptomatology, diagnostics, and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.

Evaluation of Initial Enoxaparin Dosing and Antifactor Xa Levels in Infants Admitted to the Neonatal Intensive Care Unit.

Introduction: Infants are at risk for thrombotic conditions due to multiple risk factors such as congenital heart defects and sepsis. According to the American College of Chest Physicians (ACCP) 2012 guidelines, enoxaparin may be given for thrombotic conditions at a dose of 1.5 mg/kg/dose every 12 h for patients less than 2 months of age and 1 mg/kg/dose every 12 h for those older than 2 months. Several studies have reported that infants typically require a higher initial dose of enoxaparin to reach therapeutic antifactor Xa levels than what is currently recommended. Methods: This is a single-center retrospective case-control study of hospitalized infants less than 12 months of age who received treatment with enoxaparin while admitted to the neonatal intensive care unit (NICU) at a freestanding children's hospital. The primary objective was the difference between the initial enoxaparin dose (mg/kg) compared to the enoxaparin dose in which the patient first achieved a therapeutic antifactor Xa level of 0.5-1.0 units/mL. Results: A total of 56 infants were included in this study. The median enoxaparin dose at initiation was 1.5 mg/kg/dose, and the median enoxaparin dose at the first therapeutic antifactor Xa level was 1.9 mg/kg/dose (z = -12.7, p < 0.0001). There was no correlation between gestational age and weight with the enoxaparin dose required to reach a therapeutic antifactor Xa level. Conclusion: Infants admitted to the NICU, specifically those less than 4 months of age, require higher initial enoxaparin dosing to reach therapeutic antifactor Xa levels than what is currently recommended.

The Outcomes of Patients with Omicron Variant Infection who Undergo Elective Surgery: A Propensity-score-matched Case-control Study.

Aim: To investigate whether it is safe for patients with Omicron variant infection to undergo surgery during perioperative period. Methods: A total of 3,661 surgical patients were enrolled: 3,081 who were not infected with the Omicron variant and 580 who were infected with the Omicron variant. We conducted propensity score matching (PSM) with a ratio of 1:4 and a caliper value of 0.1 to match the infected and uninfected groups based on 13 variables. After PSM, we further divided the Infected group (560 cases) by the number of days between the preoperative Omicron variant infection and surgery: 0-7, 8-14, 15-30, and >30 days. Multivariate logistic regression analysis was subsequently conducted on the categorical variables and continuous variables with a P value below 0.05, thereby comparing the infected group (0-7, 8-14, 15-30, >30 days) and the uninfected group for perioperative complications. Results: Multivariate logistic regression analysis revealed that, compared to the uninfected group, among the four subgroups of the infected patients (0-7, 8-14, 15-30, >30 days), only renal insufficiency in the 8-14 days subgroup (OR: 0.09, 95%CI 0.01-0.74, P = 0.025) and anemia in the > 30 days subgroup (OR 0.6, 95%CI 0.4-0.9, P < 0.017) showed significant difference. However, there was no statistically significant difference in the incidence rate of blood transfusion, postoperative intensive care unit transfer, lung infection/pneumonia, pleural effusion, atelectasis, respiratory failure, sepsis, postoperative deep vein thrombosis, hypoalbuminemia, urinary tract infections, and medical expenses. Conclusion: Omicron infection does not significantly increase the risk of perioperative major complications. The Omicron infection may not be a sufficient risk factor to postpone elective surgery.

Elevated Circulating Procathepsin L as a Potential Biomarker of Inflamm-aging.

Inflamm-aging is a condition of low-grade and chronic systemic inflammation characterized by a systemic increase in multiple inflammatory biomarkers such as tumor necrosis factor (TNF), interleukin 6 (IL-6), C-reactive protein (CRP), and CXCL9 (MIG) in experimental and clinical settings. However, despite the recent identification of extracellular procathepsin L (pCTS-L) as a novel mediator of inflammatory diseases such as sepsis, its possible role in inflamm-aging was previously not investigated. In the present study, we compared blood levels of pCTS-L and other 62 cytokines and chemokines between young and aged Balb/C mice by Western blotting and Cytokine Antibody Arrays. In light of the surprising finding of a marked increase in blood pCTS-L levels in aged mice, we propose that blood pCTS-L levels may serve as another biomarker of inflamm-aging. Given the capacity of pCTS-L in inducing various cytokines (e.g., TNF and IL-6), it will be important to test the hypothetic role of pCTS-L in inflamm-aging under experimental and clinical conditions.

Triglyceride-glucose index predicts sepsis-associated acute kidney injury and length of stay in sepsis: A MIMIC-IV cohort study.

Background: Inflammation and stress response may be related to the occurrence of sepsis-associated acute kidney injury (SA-AKI) in patients with sepsis.Insulin resistance (IR) is closely related to the stress response, inflammatory response, immune response and severity of critical diseases. We assume that the triglyceride-glucose (TyG) index, an alternative indicator for IR, is associated with the occurrence of SA-AKI in patients with sepsis. Methods: Data were obtained from The Medical Information Mart for Intensive Care-IV(MIMIC-IV) database in this retrospective cohort study. Univariate and multivariate logistic regression analysis and multivariate restricted cubic spline(RCS) regression were conducted to evaluate the association between TyG index and SA-AKI, length of stay (LOS). Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: The study ultimately included data from 1426 patients with sepsis, predominantly of white ethnicity (59.2%) and male sex (56.4%), with an SA-AKI incidence rate of 78.5%. A significant linear association was observed between the TyG index and SA-AKI (OR, 1.40; 95% confidence interval(CI) [1.14-1.73]). Additionally, the TyG index demonstrated a significant correlation with the length of stay (LOS) in both the hospital (ß, 1.79; 95% CI [0.80-2.77]) and the intensive care unit (ICU) (ß, 1.30; 95% CI [0.80-1.79]). Subgroup and sensitivity analyses confirmed the robustness of these associations. Conclusion: This study revealed a strong association between the TyG index and both SA-AKI and length of stay in patients with sepsis. These findings suggest that the TyG index is a potential predictor of SA-AKI and the length of hospitalization in sepsis cases, broadening its application in this context. However, further research is required to confirm whether interventions targeting the TyG index can genuinely enhance the clinical outcomes of patients with sepsis.

The 5-factor modified frailty index (mFI-5) predicts adverse outcomes after elective anterior cervical discectomy and fusion (ACDF).

Background: Anterior cervical discectomy and fusion (ACDF) is a reliable procedure commonly performed in older patients with degenerative diseases of the cervical spine. Over 130,000 procedures are performed every year with an annual increase of 5%, and overall morbidity rates can reach as high as 19.3%, indicating a need for surgeons to gauge their patients' risk for adverse outcomes. Frailty is an age-associated decline in functioning of multiple organ systems and has been shown to predict adverse outcomes following various spine procedures. There have been several proposed frailty indices of various factors including the 11-factor modified frailty index (mFI-11), which has been shown to be an effective tool for predicting complications in patients undergoing ACDF. However, there is a paucity of literature assessing the utility of the 5-factor modified frailty index (mFI-5) as a risk stratification tool for patients undergoing ACDF. The purpose of this study was to analyze the predictive capability of the mFI-5 score for 30-day postoperative adverse events following elective ACDF. Methods: A retrospective review was performed using the National Surgical Quality Improvement Program (NSQIP) database from 2010 through 2019. Patients older than 50 years of age who underwent elective ACDF were identified using Current Procedural Terminology ([CPT] codes 22554, 22551, 22552, and 63075). Exclusion criteria removed patients under the age of 51, as well as those with fractures, sepsis, disseminated cancer, a prior operation in the last 30 days, ascites, wound infection, or an emergency surgery. Patients were grouped using mFI scores of 1, 2, and 3+. Univariate analysis, using chi-squared and one-way analysis of variance (ANOVA) tests, was conducted to compare demographics, comorbidities, and postoperative complications across the varying cohorts based on mFI-5 scores. Multivariate logistic regression, including patient demographics and preoperative comorbidities as covariates, was performed to evaluate if mFI-5 scores were independent predictors of 30-day postoperative adverse events. Covariates including race, BMI, sex, ASA, and comorbidities were included in regression models. Results: The 45,991 patients were identified and allocated in cohorts based on mFI-5 score. Rates for superficial surgical site infection (SSI), organ/deep space SSI, pneumonia, progressive renal insufficiency, acute renal failure (ARF), urinary tract infection (UTI), stroke/cardiovascular accident (CVA), cardiac arrest requiring cardiopulmonary resuscitation (CPR), myocardial infarction, bleeding requiring transfusions, deep vein thrombosis/thrombophlebitis, sepsis, septic shock, readmissions, reoperation, and mortality incrementally increased with mFI-5 scores from 0 to 3+. Multivariate regression analysis revealed that mFI-5 scores 1 to 3+ increased the odds, in a stepwise manner, of total complications, cardiac arrest requiring CPR, pneumonia and mortality. MFI-5 scores of 2 and 3+ were independent predictors of readmission (2: OR=1.5, p<.001; 3+: OR=2.0, p<.001) and myocardial infarction (2: OR=3.4, p=.001; 3+: OR=6.9, p<.001). A score of 3+ increased the odds of ARF (OR=9.7, p=.022), septic shock (OR=3.6, p=.036), UTI (OR=2.1, p=.007), bleeding requiring transfusions (OR=2.1, p=.016), and reoperations (OR=1.7, p=.004). Conclusion: mFI-5 score is a quick and viable option for surgeons to use as an assessment tool to stratify high risk patients undergoing elective ACDF, as increasing mFI-5 scores showed significantly higher rates of all adverse outcomes accounted for in this study, except for deep incisional SSI, wound disruption, and PE. Additionally, moderate to severe mFI-5 scores of 2 or 3+ were independent predictors for 30-day postoperative ARF, UTI, MI, bleeding requiring transfusions, septic shock, reoperation, and readmissions following elective ACDF surgery in adults over 50 years old.

The Role of Fish Skin Xenografts in Healing Complex Wounds: A Brief Case Report.

Non-healing wounds profoundly impact patient quality of life and present a significant financial burden. The Kerecis™ fish skin xenograft is a decellularized skin matrix that has been introduced to treat complicated wounds. The objective of this presentation is to highlight the use of fish skin xenograft in the treatment of a complex right flank wound with stool contamination, necrotizing soft tissue infection due to perforated colon cancer, and sepsis. This presentation follows the wound healing for 28 days following the operation and demonstrates the efficacy of fish skin xenografts in improved wound healing. A 61-year-old female with a past medical history of colon cancer and recent chemotherapy treatment presented with colon perforation causing right flank cellulitis and sepsis with necrotic abdominal wall tissue extending into the hip joint. She was taken for an emergent exploratory laparotomy, drainage of abdominal and retroperitoneal abscesses, open right hemicolectomy, diverting ileostomy, abdominal washout, intra-abdominal omental patch, placement of Strattice mesh, and debridement of necrotizing soft tissue infection of the right flank. After extensive debridement of her 15x10cmx5cm deep wound and placement of a Kerecis™ fish skin xenograft, the wound had completely healed with excellent granulation tissue, and the patient was scheduled for placement of a skin graft 28 days following the initial procedure. The results after xenograft application were outstanding, supporting the use of polyunsaturated fatty acid (PUFA) based xenografts in wound treatment due to their anti-inflammatory and angiogenic properties. This is definitely an option that needs to be considered in expediting the healing process for complex wounds.

Surviving Postpartum Group A Streptococcus Sepsis Complicated by Multiorgan System Failure: A Complex Case Presentation.

Postpartum group A streptococcal (GAS) sepsis is a rare obstetric complication with severe clinical implications and high morbidity and mortality, presenting diagnostic and management challenges. This report analyzes a complex case of postpartum GAS sepsis, highlighting the importance of understanding the pathophysiology and clinical trajectories of this often fatal pathogen. A comprehensive analysis was conducted on a patient with postpartum GAS sepsis. Literature review and case comparisons informed the study's context. Medical history, clinical presentation, diagnostic procedures, interventions, and outcomes were reviewed and documented. The patient presented on postpartum day 5 with abdominal pain and vaginal bleeding. Her condition rapidly deteriorated, requiring aggressive interventions and systemic support. Blood cultures confirmed GAS bacteremia. She developed toxic shock syndrome, cardiomyopathy with acute cardiac failure, and seizures secondary to subdural empyema. Multidisciplinary care facilitated eventual clinical recovery. Obstacles in achieving treatment balance were evident, underscoring the systemic nature of GAS infection and the significance of interdisciplinary collaboration. This case underscores the complex pathophysiology of postpartum GAS sepsis and the importance of prompt treatment initiation, aggressive intervention, and a multidisciplinary approach to management. The study contributes to the understanding of disease progression and clinical management in severe peripartum infections, reaffirming the need for further research to improve outcomes.

Association Between Medicare's Sepsis Reporting Policy (SEP-1) and the Documentation of a Sepsis Diagnosis in the Clinical Record.

STUDY DESIGN: Interrupted time series analysis of a retrospective, electronic health record cohort. OBJECTIVE: To determine the association between the implementation of Medicare's sepsis reporting measure (SEP-1) and sepsis diagnosis rates as assessed in clinical documentation. BACKGROUND: The role of health policy in the effort to improve sepsis diagnosis remains unclear. PATIENTS AND METHODS: Adult patients hospitalized with suspected infection and organ dysfunction within 6 hours of presentation to the emergency department, admitted to one of 11 hospitals in a multi-hospital health system from January 2013 to December 2017. Clinician-diagnosed sepsis, as reflected by the inclusion of the terms "sepsis" or "septic" in the text of clinical notes in the first two calendar days following presentation. RESULTS: Among 44,074 adult patients with sepsis admitted to 11 hospitals over 5 years, the proportion with sepsis documentation was 32.2% just before the implementation of SEP-1 in the third quarter of 2015 and increased to 37.3% by the fourth quarter of 2017. Of the 9 post-SEP-1 quarters, 8 had odds ratios for a sepsis diagnosis >1 (overall range: 0.98-1.26; P value for a joint test of statistical significance = 0.005). The effects were clinically modest, with a maximum effect of an absolute increase of 4.2% (95% CI: 0.9-7.8) at the end of the study period. The effect was greater in patients who did not require vasopressors compared with patients who required vasopressors (P value for test of interaction = 0.02). CONCLUSIONS: SEP-1 implementation was associated with modest increases in sepsis diagnosis rates, primarily among patients who did not require vasoactive medications.

Changing Landscape of Antimicrobial Resistance in Neonatal Sepsis: An in silico Analyses of Multidrug Resistance in Klebsiella pneumoniae.

BACKGROUND: Neonatal sepsis poses a critical healthcare concern, as multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) infections are on the rise. Understanding the antimicrobial susceptibility patterns and underlying resistance mechanism is crucial for effective treatment. OBJECTIVES: This study aimed to comprehensively investigate the antimicrobial susceptibility patterns of K. pneumoniae strains responsible for neonatal sepsis using in silico tools. We sought to identify trends and explore reasons for varying resistance levels, particularly for ß-lactams and fluoroquinolone. METHODS: K. pneumoniae isolated from neonates at Kanchi Kamakoti CHILDS Trust Hospital (2017-2020) were analyzed for antimicrobial resistance. Elevated resistance to ß-lactam and fluoroquinolone antibiotics was further investigated through molecular docking and interaction analysis. ß-lactam affinity with penicillin-binding proteins and ß-lactamases was examined. Mutations in ParC and GyrA responsible for quinolone resistance were introduced to investigate ciprofloxacin interactions. RESULTS: Of 111 K. pneumoniae blood sepsis isolates in neonates, high resistance was detected to ß-lactams such as cefixime (85.91%, n = 71), ceftriaxone (84.9%, n = 106), cefotaxime (84.9%, n = 82) and fluoroquinolone (ciprofloxacin- 79.44%, n = 107). Molecular docking revealed low ß-lactam binding toward penicillin-binding proteins and higher affinities for ß-lactamases, attributing to the reduced ß-lactam efficiency. Additionally, ciprofloxacin showed decreased affinity toward mutant ParC and GyrA in comparison to their corresponding wild-type proteins. CONCLUSION: Our study elucidates altered resistance profiles in neonatal sepsis caused by K. pneumoniae, highlighting mechanisms of ß-lactam and fluoroquinolone resistance. It underscores the urgent need for the development of sustainable therapeutic alternatives to address the rising antimicrobial resistance in neonatal sepsis.

Clinical Course and Outcomes of Infants with Streptococcus bovis/Streptococcus Gallolyticus subspecies pasteurianus Infection: A Systematic Review and Meta-analysis.

BACKGROUND: Streptococcus gallolyticus subspecies pasteurianus (SGP), a subtype of Streptococcus bovis, is an uncommon but important cause of neonatal sepsis. Although uncommon, SGP infections during infancy have been associated with an increased risk of morbidity and mortality. METHODS: This is a systematic review and meta-analysis of available literature on the clinical course and outcomes of infants with SGP infection. Studies were identified using the following MeSH keywords: "Streptococcus gallolyticus," "Streptococcus bovis," "newborn" and "infant." Data including perinatal factors, clinical presentation, investigations, treatment and outcomes were extracted and analyzed. RESULTS: A total of 46 articles were identified (116 cases: 60 S. bovis, 56 SGP). The cases were predominantly term (52%), male (57%) and born via vaginal delivery (67%). The most common symptom was fever [67% (95% confidence interval (CI): 43%-84%)], lethargy [66% (95% CI: 32%-89%)], tachypnea [59% (95% CI: 27%-85%)] and irritability [59% (95% CI: 34%-79%)]. Infants with early-onset infections (<3 days of life) were more likely to have respiratory symptoms and bacteremia (73%), whereas late-onset infections presented predominantly with gastrointestinal symptoms. Four mortalities were reported which occurred before antibiotic administration. Isolated bacteria were mostly penicillin-susceptible [95% (95% CI: 78-99%)] and cases treated with penicillin derivative had good recovery. CONCLUSIONS: SGP is an important cause of neonatal sepsis and meningitis. Penicillin derivative is an effective treatment for SGP, and outcomes appear to be favorable.

Application of AI in Sepsis: Citation Network Analysis and Evidence Synthesis.

BACKGROUND: Artificial intelligence (AI) has garnered considerable attention in the context of sepsis research, particularly in personalized diagnosis and treatment. Conducting a bibliometric analysis of existing publications can offer a broad overview of the field and identify current research trends and future research directions. OBJECTIVE: The objective of this study is to leverage bibliometric data to provide a comprehensive overview of the application of AI in sepsis. METHODS: We conducted a search in the Web of Science Core Collection database to identify relevant articles published in English until August 31, 2023. A predefined search strategy was used, evaluating titles, abstracts, and full texts as needed. We used the Bibliometrix and VOSviewer tools to visualize networks showcasing the co-occurrence of authors, research institutions, countries, citations, and keywords. RESULTS: A total of 259 relevant articles published between 2014 and 2023 (until August) were identified. Over the past decade, the annual publication count has consistently risen. Leading journals in this domain include Critical Care Medicine (17/259, 6.6%), Frontiers in Medicine (17/259, 6.6%), and Scientific Reports (11/259, 4.2%). The United States (103/259, 39.8%), China (83/259, 32%), United Kingdom (14/259, 5.4%), and Taiwan (12/259, 4.6%) emerged as the most prolific countries in terms of publications. Notable institutions in this field include the University of California System, Emory University, and Harvard University. The key researchers working in this area include Ritankar Das, Chris Barton, and Rishikesan Kamaleswaran. Although the initial period witnessed a relatively low number of articles focused on AI applications for sepsis, there has been a significant surge in research within this area in recent years (2014-2023). CONCLUSIONS: This comprehensive analysis provides valuable insights into AI-related research conducted in the field of sepsis, aiding health care policy makers and researchers in understanding the potential of AI and formulating effective research plans. Such analysis serves as a valuable resource for determining the advantages, sustainability, scope, and potential impact of AI models in sepsis.

Infectious Diseases: What You May Have Missed in 2023.

In 2023, published research on COVID-19 remains prominent. The aim of this article is to highlight important developments in infectious disease evidence unrelated to COVID-19 that were published in 2023. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The highlighted publications relate to various organisms and patient populations. One article provides insight into the updated guidelines for the diagnosis and management of infective endocarditis. Several articles address the management of sepsis and bacteremia: comparison of cefepime versus piperacillin-tazobactam, ceftobiprole for the treatment of complicated Staphylococcus aureus bacteremia, and early switch from intravenous to oral antibiotics in patients with gram-negative bacteremia. Another article examines differences in all-cause mortality in patients with Clostridioides difficile infection who receive different treatments. Additional articles provide evidence about the treatment of patients with HIV infection: the utility of preexposure prophylaxis to prevent HIV infection, the efficacy of pitavastatin in reducing cardiovascular disease, and the efficacy of dexamethasone for the treatment of tuberculous meningitis in persons with HIV.