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ObjectiveThis study aimed to assess the International Quality Improvement Collaborative single-site data from a developing country to identify trends in outcomes and factors associated with poor outcomes. DesignRetrospective descriptive study. SettingThe National Institute of Cardiovascular Diseases, Karachi, Pakistan. ParticipantsPatients undergoing surgery for congenital heart disease (CHD). Outcome measureKey factors were examined, including preoperative, procedural and demographic data, as well as surgical complications and outcomes. We identified risk factors for mortality, bacterial sepsis and 30-day mortality using multivariable logistic regression. ResultsA total of 3367 CHD surgical cases were evaluated; of these, 59.4% (2001) were male and 82.8% (2787) were between the ages of 1 and 17 years. Only 0.2% (n=6) were infants (≤30 days) and 2.3% (n=77) were adults (≥18 years). The in-hospital mortality rate was 6.7% (n=224), and 4.4% (n=147) and 0.8% (n=27) had bacterial sepsis and surgical site infections, respectively. The 30-day status was known for 90.8% (n=3058) of the patients, of whom 91.6% (n=2800) were alive. On multivariable analysis, the adjusted OR for in-hospital mortality was 0.40 (0.29–0.56) for teenagers compared with infancy/childhood and 1.95 (1.45–2.61) for patients with oxygen saturation

OBJECTIVES: Compliance with the fluid bonus component of the SEP-1 (severe sepsis and septic shock management) bundle remains poor due to concerns for iatrogenic harm from fluid overload. We sought to assess whether patients who received focused cardiac ultrasound (FCU) and were found to be fluid tolerant (FT) were more likely to receive the recommended 30 mL/kg fluid bolus within 3 hours of sepsis identification. DESIGN: Retrospective, observational cohort study. SETTING: University-affiliated, tertiary-care hospital in the United States. PATIENTS: Emergency department patients presenting with septic shock from 2018 to 2021. The primary exposure was receipt of FCU with identification of fluid tolerance 3 hours from onset of septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-two of 1,024 patients with septic shock received FCU within 3 hours of sepsis onset. One hundred seventy-seven were determined to be FT. One hundred fifteen patients were determined to have poor fluid tolerance (pFT). FT patients were more likely to reach the recommended 30 mL/kg fluid bolus amount compared with pFT (FT 52.0% vs. pFT 31.3%, risk difference: 20.7%, [95% CI, 9.4–31.9]). Patients who did not receive FCU met the bolus requirement 34.3% of the time. FT patients received more fluid within 3 hours (FT 2,271 mL vs. pFT 1,646 mL, mean difference 625 mL [95% CI, 330–919]). Multivariable logistic regression was used to estimate the association between fluid tolerance FCU findings and compliance with 30 mL/kg bolus after adjustment for patient characteristics and markers of hemodynamic instability. FT with associated with a higher likelihood of meeting bolus requirement (odds ratio 2.17 [1.52–3.12]). CONCLUSIONS: Patients found to be FT by FCU were more likely to receive the recommended 30 mL/kg bolus in the SEP-1 bundle when compared with patients found with pFT or those that did not receive FCU. There was no difference between groups in 28-day mortality, vasopressor requirement, or need for mechanical ventilation.

IMPORTANCE: The interhospital transfer (IHT) of patients with sepsis to higher-capability hospitals may improve outcomes. Little is known about patient and hospital factors associated with sepsis IHT. OBJECTIVES: We evaluated patterns of hospitalization and IHT and determined patient and hospital factors associated with the IHT of adult patients with sepsis. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 349,938 adult patients with sepsis at 329 nonfederal hospitals in California, 2018–2019. MAIN OUTCOMES AND MEASURES: We evaluated patterns of admission and outward IHT between low sepsis-, intermediate sepsis-, and high sepsis-capability hospitals. We estimated odds of IHT using generalized estimating equations logistic regression with bootstrap stepwise variable selection. RESULTS: Among the cohort, 223,202 (66.4%) were initially hospitalized at high-capability hospitals and 10,870 (3.1%) underwent IHT. Nearly all transfers (98.2%) from low-capability hospitals were received at higher-capability hospitals. Younger age (< 65 yr) (adjusted odds ratio [aOR] 1.54; 95% CI, 1.40–1.69) and increasing organ dysfunction (aOR 1.22; 95% CI, 1.19–1.25) were associated with higher IHT odds, as were admission to low-capability (aOR 2.79; 95% CI, 2.33–3.35) or public hospitals (aOR 1.35; 95% CI, 1.09–1.66). Female sex (aOR 0.88; 95% CI, 0.84–0.91), Medicaid insurance (aOR 0.59; 95% CI, 0.53–0.66), home to admitting hospital distance less than or equal to 10 miles (aOR 0.92; 95% CI, 0.87–0.97) and do-not-resuscitate orders (aOR 0.48; 95% CI, 0.45–0.52) were associated with lower IHT odds, as was admission to a teaching hospital (aOR 0.83; 95% CI, 0.72–0.96). CONCLUSIONS AND RELEVANCE: Most patients with sepsis are initially hospitalized at high-capability hospitals. The IHT rate for sepsis is low and more likely to originate from low-capability and public hospitals than from high-capability and for-profit hospitals. Transferred patients with sepsis are more likely to be younger, male, sicker, with private medical insurance, and less likely to have care limitation orders. Future studies should evaluate the comparative benefits of IHT from low-capability hospitals.

by Petek Eylul Taneri, Jamie J. Kirkham, Eleanor J. Molloy, Linda Biesty, Richard A. Polin, James L. Wynn, Barbara J. Stoll, Niranjan Kissoon, Kondwani Kawaza, Mandy Daly, Aoife Branagan, Lívia Nagy Bonnard, Eric Giannoni, Tobias Strunk, Magdalena Ohaja, Kenneth Mugabe, Denise Suguitani, Fiona Quirke, Declan Devane Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients’ parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.

Abstract Objective To evaluate the association between traditional laboratory findings and death, and to find risk factors for death in infants with early onset sepsis (EOS). Study design This was a single-center, case–control, retrospective trial conducted between January 2020 and August 2021. Infants with EOS were enrolled and divided into two groups based on outcome before hospital discharge: non-survivors (Mortality group) and survivors (Survival group). Results Out of 556 eligible neonates, there were 38 (6.8%) deaths. After univariate analysis and ROC curve analysis, there were a total of 12 values with significant differences (p 

Abstract Introduction The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. Methods PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. Results Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14–2.48, P-value 

Abstract Objective To evaluate the association between traditional laboratory findings and death, and to find risk factors for death in infants with early onset sepsis (EOS). Study design This was a single-center, case–control, retrospective trial conducted between January 2020 and August 2021. Infants with EOS were enrolled and divided into two groups based on outcome before hospital discharge: non-survivors (Mortality group) and survivors (Survival group). Results Out of 556 eligible neonates, there were 38 (6.8%) deaths. After univariate analysis and ROC curve analysis, there were a total of 12 values with significant differences (p 

Objectives: We hypothesized that the immunosuppressive effects associated with antibiotics, sedatives, and catecholamines amplify sepsis-associated immune suppression through mitochondrial dysfunction, and there is a cumulative effect when used in combination. We thus sought to determine the impact of the exemplar drugs ciprofloxacin, propofol, and norepinephrine, used alone and in combination, at clinically relevant concentrations, on the ex vivo functionality of peripheral blood mononuclear cells (PBMCs) drawn from healthy, infected, and septic individuals. Design: In vitro/ex vivo investigation. Setting: University laboratory. Subjects: Healthy volunteers, infected (nonseptic) patients in the emergency department, and septic ICU patients. Interventions: PBMCs were isolated from these subjects and treated with ciprofloxacin (100 µg/mL), propofol (50 µg/mL), norepinephrine (10 µg/mL), or all three drugs combined, with and without lipopolysaccharide (100 ng/mL) for 6 or 24 hours. Comparison was made between study groups and against untreated cells. Measurements were made of cell viability, cytokine production, phagocytosis, human leukocyte antigen-DR (HLA-DR) status, mitochondrial membrane potential, mitochondrial reactive oxygen species production, and oxygen consumption. Gene expression in immune and metabolic pathways was investigated in PBMCs sampled from healthy volunteers coincubated with septic serum. Measurements and Results: Coincubation with each of the drugs reduced cytokine production and phagocytosis in PBMCs isolated from septic patients, and healthy volunteers coincubated with septic serum. No effect was seen on HLA-DR surface expression. No cumulative effects were seen with the drug combination. Sepsis-induced changes in gene expression and mitochondrial functionality were not further affected by addition of any of the drugs. Conclusion: Drugs commonly used in critical care lead to significant immune dysfunction ex vivo and enhance sepsis-associated immunosuppression. Further studies are required to identify underlying mechanisms and potential impact on patient outcomes.

In this Medical News article, Johns Hopkins University computer scientist Suchi Saria, PhD, MSc, discusses the use of AI tools in early sepsis detection and other clinical applications.

Abstract Introduction The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. Methods PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. Results Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14–2.48, P-value 

Abstract Introduction The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. Methods PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. Results Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14–2.48, P-value 

Abstract Introduction The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. Methods PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. Results Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14–2.48, P-value 

by Min Xiao, Hongbin Deng, Wenjian Mao, Yang Liu, Qi Yang, Yuxiu Liu, Jiemei Fan, Weiqin Li, Dadong Liu Background Sepsis is characterized by upregulated lipolysis in adipose tissue and a high blood triglyceride (TG) level. It is still debated whether serum TG level is related to mortality in septic patients. The aim of this study is to investigate the association between serum TG level and mortality in septic patients admitted to the intensive care unit (ICU). Methods Data from adult septic patients (≥18 years) admitted to the ICU for the first time were obtained from the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database. The patients’ serum TG levels that were measured within the first week after ICU admission were extracted for statistical analysis. The endpoints were 28-day, ICU and in-hospital mortality. Results A total of 2,782 septic patients were included. Univariate analysis indicated that the relationship between serum TG levels and the risk of mortality was significantly nonlinear. Both the Lowess smoothing technique and restricted cubic spline analyses revealed a U-shaped association between serum TG levels and mortality among septic patients. The lowest mortality rate was associated with a serum TG level of 300–500 mg/dL. Using 300∼500 mg/dL as the reference range, we found that both hypo-TG (…

Abstract Background Sepsis in low-birth-weight neonates remains one of the most significant causes of neonatal morbidity and mortality. Approximately 3 million newborns suffer from sepsis globally every year. The aim of this study was to compare demographic and clinical features, as well as etiology and antibiotic susceptibility, of the main pathogens related to neonatal sepsis in two neonatal intensive units during a two-year period. Methods We observed early-onset (EO-BSI) and late-onset bloodstream infections (LO-BSI) cases in two high-reference neonatal intensive care units (NICU) over a 24-month period (2016–2017). Samples of patients’ blood were tested for the presence of the microorganisms. All bacterial isolates were tested for susceptibility to antibiotics. Results The majority of sepsis cases weighed above 1000 g and were born by cesarean section. About 10% of the EO-BSI group died. There were differences in the EO-BSI /LO-BSI ratio in the compared wards due to differences among the admitted children. The most common pathogens isolated from blood were coagulase-negative staphylococci (CoNS) were represented by two dominating species: S. epidermidis and S. haemolyticus, followed by Klebsiella spp. strains and E.coli, which were mostly found in EO-BSI cases. No single S. agalactiae (GBS) strain was isolated. The majority of CoNS strains were resistant to methicillin, half were resistant to aminoglycosides, and one-third were resistant to macrolides and lincosamides. Half of the Gram-negative rods were resistant to beta-lactams. Conclusions The epidemiology of sepsis in two observed NICUs is comparable to data obtained from other studies with a predominance of methicillin-resistant CoNS in LO-BSI and beta-lactam resistant E. coli in EO-BSI. It is of importance that the campaign for controlling GBS carriage in pregnant women in Poland resulted in the disappearance of GBS as a cause of sepsis. Unfortunately, there are no such measures to control E.coli related sepsis. …

Abstract Background Sepsis in low-birth-weight neonates remains one of the most significant causes of neonatal morbidity and mortality. Approximately 3 million newborns suffer from sepsis globally every year. The aim of this study was to compare demographic and clinical features, as well as etiology and antibiotic susceptibility, of the main pathogens related to neonatal sepsis in two neonatal intensive units during a two-year period. Methods We observed early-onset (EO-BSI) and late-onset bloodstream infections (LO-BSI) cases in two high-reference neonatal intensive care units (NICU) over a 24-month period (2016–2017). Samples of patients’ blood were tested for the presence of the microorganisms. All bacterial isolates were tested for susceptibility to antibiotics. Results The majority of sepsis cases weighed above 1000 g and were born by cesarean section. About 10% of the EO-BSI group died. There were differences in the EO-BSI /LO-BSI ratio in the compared wards due to differences among the admitted children. The most common pathogens isolated from blood were coagulase-negative staphylococci (CoNS) were represented by two dominating species: S. epidermidis and S. haemolyticus, followed by Klebsiella spp. strains and E.coli, which were mostly found in EO-BSI cases. No single S. agalactiae (GBS) strain was isolated. The majority of CoNS strains were resistant to methicillin, half were resistant to aminoglycosides, and one-third were resistant to macrolides and lincosamides. Half of the Gram-negative rods were resistant to beta-lactams. Conclusions The epidemiology of sepsis in two observed NICUs is comparable to data obtained from other studies with a predominance of methicillin-resistant CoNS in LO-BSI and beta-lactam resistant E. coli in EO-BSI. It is of importance that the campaign for controlling GBS carriage in pregnant women in Poland resulted in the disappearance of GBS as a cause of sepsis. Unfortunately, there are no such measures to control E.coli related sepsis. …

Abstract Background Trueperella pyogenes (T. pyogenes) is a bacterium that colonizes the skin and mucosal surfaces of various domestic and wild animals. It rarely leads to infections in humans, with only a few descriptions available in the literature. Case presentation A 71-year-old Swiss farmer with a history of recurring basal cell carcinoma and metastasized pancreatic neuroendocrine tumor presented with signs of sepsis after a three-day history of general weakness, malaise and fever. Clinical and echocardiographic findings, as well as persistent bacteremia were consistent with mitral valve endocarditis caused by T. pyogenes. The patient’s condition gradually improved under antibiotic treatment with piperacillin/tazobactam (empiric therapy of sepsis), and later penicillin G based on resistance testing. He was discharged after 13 days and continued outpatient antibiotic therapy with ceftriaxone, resulting in a total antibiotic treatment duration of six weeks. This is the first literature review of T. pyogenes endocarditis in humans. Among nine cases of T. pyogenes endocarditis, three patients had documented contact with farm animals and five had an underlying condition that compromised the immune system. While antibiotic resistance of T. pyogenes is an emerging concern, susceptibility to beta-lactam antibiotics seems to persist. The mortality of T. pyogenes endocarditis described in the literature was high, with 66% of patients not surviving the disease. Conclusions T. pyogenes is a rare causative organism of infectious endocarditis in humans and descriptions are mainly restricted to case reports. In our review of the literature, we found that both an impaired immune system and contact with farm animals might be risk factors. Growth of T. pyogenes in blood cultures is unlikely to be missed during routine analysis, as it shows marked beta-hemolysis on blood agar culture plates, which generally leads to further characterization of the bacteria. Susceptibility to penicillin, ceftriaxone, and macrolides seems to be retained and the reported mortality in the few patients with T. pyogenes endocarditis is high. …

Abstract Purpose Clinical and direct medical cost data on RSV-related hospitalizations are relevant for public health decision-making. We analyzed nationwide data on RSV-coded hospitalizations from Germany in different age and risk groups. Methods Assessment of RSV-coded hospitalizations (ICD-10-GM RSV code J12.1/J20.5/J21.0 as primary discharge diagnosis) from 01/2010 to 12/2019, using remote data retrieval from the Hospital Statistics Database of the German Federal Statistical Office. Results Overall, 130,084 RSV-coded hospitalizations (123,091 children  59 years) were reported (median age 

Abstract The central nervous system is one of the most common sites of aspergillosis involvement in immunocompromised people, just after sinopulmonary infections. Neuroimaging modalities are crucial for the diagnosis of cerebral aspergillosis (CA). Here, we describe a rare case of concurrent mixed aspergillosis infection with Aspergillus fumigatus and Aspergillus niger in a 2-year-old leukemic boy. The first neuroimaging finding, which was followed by focal seizures, was recognized as extensive cerebral hemorrhage in the absence of thrombocytopenia and coagulopathy. As the patient survived for more than 4 months after diagnosis, we were able to perform a neuroimaging evaluation during long-term observation. In serial neuroimaging studies, a secondary fungal abscess was observed at the site of hemorrhagic infarctions. Finally, the patient died from bacterial sepsis. In this case study, we try to categorize the neuroimaging findings of CA into distinct phases to better understand how CA changes over time. …

Objective: Sepsis is a leading cause of mortality. Predicting outcomes is challenging and few biomarkers perform well. Defects in the renin–angiotensin system (RAS) can predict clinical outcomes in sepsis and may outperform traditional biomarkers. We postulated that RAS dysfunction (elevated active renin, angiotensin 1-7 [Ang-(1-7)], and angiotensin-converting enzyme 2 (ACE2) activity with depressed Ang-II and ACE activity) would be associated with mortality in a cohort of septic patients. Design: Post hoc analysis of patients enrolled in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized controlled trial. Setting: Forty-three hospitals across the United States. Patients: Biorepository samples of 103 patients. Interventions: We analyzed day 0 (within 24 hr of respiratory failure, septic shock, or both) and day 3 samples (n = 103 and 95, respectively) for assessment of the RAS. The association of RAS values with 30-day mortality was determined using Cox proportional hazards regression with multivariable adjustments for age, sex, VICTAS treatment arm, systolic blood pressure, Sequential Organ Failure Assessment Score, and vasopressor use. Measurements and Main Results: High baseline active renin values were associated with higher 30-day mortality when dichotomized to the median of 188.7 pg/mL (hazard ratio [HR] = 2.84 [95% CI, 1.10–7.33], p = 0.031) or stratified into quartiles (Q1 = ref, HRQ2 = 2.01 [0.37–11.04], HRQ3 = 3.22 [0.64–16.28], HRQ4 = 5.58 [1.18–26.32], p for linear trend = 0.023). A 1-sd (593.6 pg/mL) increase in renin from day 0 to day 3 was associated with increased mortality (HR = 3.75 [95% CI, 1.94–7.22], p < 0.001), and patients whose renin decreased had improved survival compared with those whose renin increased (HR 0.22 [95% CI, 0.08–0.60], p = 0.003). Ang-(1-7), ACE2 activity, Ang-II and ACE activity did not show this association. Mortality was attenuated in patients with renin over the median on day 0 who received the VICTAS intervention, but not on day 3 (p interaction 0.020 and 0.137, respectively). There were no additional consistent patterns of mortality on the RAS from the VICTAS intervention. Conclusions: Baseline serum active renin levels were strongly associated with mortality in critically ill patients with sepsis. Furthermore, a greater relative activation in circulating renin from day 0 to day 3 was associated with a higher risk of death.

Abstract Purpose Clinical and direct medical cost data on RSV-related hospitalizations are relevant for public health decision-making. We analyzed nationwide data on RSV-coded hospitalizations from Germany in different age and risk groups. Methods Assessment of RSV-coded hospitalizations (ICD-10-GM RSV code J12.1/J20.5/J21.0 as primary discharge diagnosis) from 01/2010 to 12/2019, using remote data retrieval from the Hospital Statistics Database of the German Federal Statistical Office. Results Overall, 130,084 RSV-coded hospitalizations (123,091 children  59 years) were reported (median age 

To the Editor The MERCY randomized clinical trial in critically ill patients with sepsis found that the meropenem dosing strategy (continuous infusion vs intermittent bolus) did not improve the composite outcome of mortality and emergence of drug-resistant bacteria. However, we are concerned that the population for whom the administration of meropenem as a continuous infusion is expected to be most beneficial was not well represented in the trial.

In Reply Augmented kidney clearance (defined as a GFR ≥130 mL/min/1.73 m2) may increase meropenem clearance, resulting in a lower chance of achieving a target plasma concentration with a bolus administration. Augmented kidney clearance occurs in approximately 20% of patients with critical illness, especially in younger patients, in those with burns, and during the first week of hospital admission. None of these circumstances were frequent in the MERCY trial; patients were older (mean age, 64 years) and mainly had respiratory infections (33% of patients). Meropenem therapy was usually initiated later than 1 week after hospital admission, following failure of other antibiotics (66% were already receiving treatment at randomization).

Abstract Purpose This study investigated the clinical and antimicrobial characteristics of Acinetobacter spp. bloodstream infection (BSI) in hematological patients. Risk factors for 30-day mortality and carbapenem-resistant Acinetobacter spp. (CRA) BSI acquisition were also identified. Methods We reviewed forty hematological patients with Acinetobacter spp. BSI in a large Chinese blood disease hospital between 2013 and 2022. The remaining CRA isolates were subjected to whole-genome sequencing. Results The 30-day mortality rate was high at 35%. Hematological patients with Acinetobacter spp. BSI often presented with severe conditions and co-infections at multiple sites. All strains were colistin-susceptible and 40.0% were CR. Multivariate analysis identified several risk factors associated with CRA BSI acquisition, including previous exposure to carbapenems within 30 days and CRA colonization. Very severe aplastic anaemia, tetracycline-resistant Acinetobacter spp. BSI, and unresolved neutropenia after infection were closely associated with 30-day mortality. Non-survivors often presented with higher median PCT and CRP levels and severe complications, such as intracranial infection, cardiac dysfunction, respiratory failure, and severe sepsis or septic shock. Our study also identified inappropriate empirical antibiotic therapy as an independent predictor of 30-day mortality (OR: 11.234, 95% CI: 1.261–20.086, P = 0.030). This study was the first to report A. oleivorans as a human pathogen, and to identify its unique oxacillinase, OXA-325. Conclusion An environment-originated non-pathogenic species can become pathogenic when the body’s immunity is compromised. Our results also highlighted the importance of improving neutropenia after infection, treating severe organ dysfunction, and administering appropriate empirical antibiotic therapy to reduce mortality in this patient population. …

OBJECTIVES: To identify opportunities for improving hospital-based sepsis care and to inform an ongoing statewide quality improvement initiative in Michigan. DESIGN: Surveys on hospital sepsis processes, including a self-assessment of practices using a 3-point Likert scale, were administered to 51 hospitals participating in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan, at two time points (2020, 2022). Forty-eight hospitals also submitted sepsis protocols for structured review. SETTING: Multicenter quality improvement consortium. SUBJECTS: Fifty-one hospitals in Michigan. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the included hospitals, 92.2% (n = 47/51) were nonprofit, 88.2% (n = 45/51) urban, 11.8% (n = 6/51) rural, and 80.4% (n = 41/51) teaching hospitals. One hundred percent (n = 51/51) responded to the survey, and 94.1% (n = 48/51) provided a sepsis policy/protocol. All surveyed hospitals used at least one quality improvement approach, including audit/feedback (98.0%, n = 50/51) and/or clinician education (68.6%, n = 35/51). Protocols included the Sepsis-1 (18.8%, n = 9/48) or Sepsis-2 (31.3%, n = 15/48) definitions; none (n = 0/48) used Sepsis-3. All hospitals (n = 51/51) used at least one process to facilitate rapid sepsis treatment, including order sets (96.1%, n = 49/51) and/or stocking of commonly used antibiotics in at least one clinical setting (92.2%, n = 47/51). Treatment protocols included guidance on antimicrobial therapy (68.8%, n = 33/48), fluid resuscitation (70.8%, n = 34/48), and vasopressor administration (62.5%, n = 30/48). On self-assessment, hospitals reported the lowest scores for peridischarge practices, including screening for cognitive impairment (2.0%, n = 1/51 responded “we are good at this”) and providing anticipatory guidance (3.9%, n = 2/51). There were no meaningful associations of the Centers for Medicare and Medicaid Services’ Severe Sepsis and Septic Shock: Management Bundle performance with differences in hospital characteristics or sepsis policy document characteristics. CONCLUSIONS: Most hospitals used audit/feedback, order sets, and clinician education to facilitate sepsis care. Hospitals did not consistently incorporate organ dysfunction criteria into sepsis definitions. Existing processes focused on early recognition and treatment rather than recovery-based practices.

OBJECTIVES: Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies—lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes. DESIGN: Genetic and clinical epidemiology, and experimental models. SETTING: Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. PATIENTS OR SUBJECTS: Nine human cohorts with sepsis (total n = 12,514) were assessed for an association between sepsis mortality and PCSK9 loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in Pseudomonas aeruginosa and Staphylococcus aureus bacteremia sepsis models, and in lipopolysaccharide-induced animal models. INTERVENTIONS: Observational human cohort studies used genetic PCSK9 LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis. MEASUREMENTS AND MAIN RESULTS: Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 LOF was odds ratio = 0.86 (95% CI, 0.67–1.10; p = 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32–1.20; p = 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival. CONCLUSIONS: PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.

Challenging conventional wisdom is important and frequently useful. Septic shock is a form of distributive shock in which hypotension results from vasodilation. Although myocardial performance may not always be entirely normal, a phenomenon termed septic cardiomyopathy, cardiac output is usually preserved, in part by increased heart rate. Therapy of septic shock refractory to fluid administration entails administration of vasopressor agents; norepinephrine is generally preferred as an initial agent. In those cases in which cardiac output is felt to be low enough to compromise perfusion, inotropic agents may be used. In this context, use of β-blockers may well be regarded as counterintuitive inasmuch as their hemodynamic effects would tend to decrease arterial pressure and cardiac output. Despite this, investigators have challenged conventional wisdom and evaluated the effects of β-blockade for treating sepsis.

This Viewpoint discusses Hospital Sepsis Program Core Elements, a set of guidance provided by the Centers for Disease Control and Prevention to help hospitals develop multiprofessional programs that monitor and optimize management and outcomes of sepsis.

Abstract Background The efficacy of antiviral drugs that neutralize antibody drugs and fight against SARS-COV-2 is reported to be attenuated by genetic mutations of the virus in vitro. When B-cell immunocompromised patients are infected with SARS-COV-2, the infection can be prolonged, and genetic mutations can occur during the course of treatment. Therefore, for refractory patients with persistent COVID-19 infection, genomic analysis was performed to obtain data on drug resistance mutations as a reference to determine which antiviral drugs and antibody therapies might be effective in their treatment. Methods This was a descriptive analysis with no controls. Patients were diagnosed as having COVID-19, examined, and treated in the Kansai Medical University General Medical Center between January 2022 and January 2023. The subjects of the study were B-cell immunocompromised patients in whom genome analysis of SARS-CoV-2 was performed. Results During the study period, 984 patients with COVID-19 were treated at our hospital. Of those, 17 refractory cases underwent genomic analysis. All 17 patients had factors related to immunodeficiency, such as malignant lymphoma or post-organ transplantation. Eleven patients started initial treatment for COVID-19 at our hospital, developed persistent infection, and underwent genomic analysis. Six patients who were initially treated for COVID-19 at other hospitals became persistently infected and were transferred to our hospital. Before COVID-19 treatment, genomic analysis showed no intrahost mutations in the NSP5, the NSP12, and the RBD regions. After COVID-19 treatment, mutations in these regions were found in 12 of 17 cases (71%). Sixteen patients survived the quarantine, but one died of sepsis. Conclusions In genomic analysis, more mutations were found to be drug-resistant after COVID-19 treatment than before COVID-19 treatment. Although it was not possible to demonstrate the usefulness of genome analysis for clinical application, the change of the treatment drug with reference to drug resistance indicated by genomic analysis may lead to good outcome of immunocompromised COVID-19 patients. …