Sepsis Current Awareness Bulletin July 2020

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Title: Mitochondrial Dysregulation in Sepsis: A Literature Review. Citation: Clinical Nurse Specialist: The Journal for Advanced Nursing Practice; Jul 2020; vol. 34 (no. 4); p. 170-177 Author(s): Graham ; Stacy, Kathleen Background: Until 2016, the condition Sepsis was widely understood to be the systemic immune response syndrome in the presence or suspicion of an infectious source. Systemic immune response syndrome, an adaptive response, has been repeatedly demonstrated to lack specificity for sepsis. The current definition of sepsis describes a dysregulated host response to infection, yet the dysregulated nature of the response has yet to be defined. Successful recognition and management of sepsis are critically dependent on understanding and operationalizing the definition of sepsis. Objective: The authors sought to review the current literature on sepsis and its relationship to oxygen downregulation within the mitochondria along the electron transport chain. Methods: Articles retrieved from databases PubMed and CINAHL, pertaining to human cells, post 2001, in English, original experimental, quasi-experimental, or cohort design. Articles were selected and retrieved by the first author and synthesized by both authors. Results: The 10 articles included in the review were all bench science cellular studies. They demonstrated consistent, statistically significant differences when investigating mitochondrial oxygen downregulation in sepsis versus control, offering strong, statistically significant support for the hypothesis of mitochondrial dysregulation in the septic host. Conclusions: The evidence makes a compelling case for mitochondrial dysregulation to inform the current definition of sepsis as a dysregulated host response. As the evidence points to a linear, progressive time/exposure-dependent disruption in oxygen downregulation in sepsis at the cellular level, it lends credence to the recommendations for early intervention and its relationship with survivability. Time is not on the side of the individual with sepsis.

Title: Association of weekend admission and clinical outcomes in hospitalized patients with sepsis: An observational study. Citation: Medicine; May 2020; vol. 99 (no. 19); p. 1-6 Author(s): Bernet ; Gut, Lara; Baechli, Ciril; Koch, Daniel; Wagner, Ulrich; Mueller, Beat; Schuetz, Philipp; Kutz, Alexander Abstract: Sepsis is associated with impaired clinical outcomes. It requires timely diagnosis and urgent therapeutic management. Because staffing during after-hours is limited, we explored whether after-hour admissions are associated with worse clinical outcomes in patients with sepsis.In this retrospective cohort study, we analyzed nationwide acute care admissions for a main diagnosis of sepsis in Switzerland between 2006 and 2016 using prospective administrative data. The primary outcome was in-hospital mortality using multivariable logistic regression models. Secondary outcomes were intensive care unit (ICU) admission, intubation, and 30-day readmission. We included 86,597 hospitalizations for sepsis, 60.1% admitted during routine-hours, 16.8% on weekends and 23.1% during night shift. Compared to routine-hours, we found a higher odds ratio (OR) for in-hospital mortality in patients admitted on weekends (Adjusted OR 1.05, 95% confidence interval [95% CI] 1.01, 1.10, P = .041). Also, the OR for ICU admission (OR 1.14, 95% CI 1.10, 1.19, P < .001) and intubation (OR 1.18, 95% CI 1.12, 1.25 P < .001) was higher for weekends compared to routine-hours. Regarding 30-day readmission, evidence for an association could not be observed. Night shift admission, compared to routine-hours, was associated with a higher OR for ICU admission and intubation (ICU admission: OR 1.28 (1.23, 1.32), P < .001; intubation: OR 1.31, 95% CI 1.25, 1.37, P < .001) but with a lower OR for in-hospital mortality (OR 0.93, 19% CI 0.89, 0.97, P = .001).Among hospitalizations with a main diagnosis of sepsis, weekend admissions were associated with higher OR for in-hospital mortality, ICU admission, and intubation. Whether these findings can be explained by staffing-level differences needs to be addressed.

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Title: Effect of Dexamethasone on Mortality in Adult and Elderly Patients with Sepsis: a Systematic Review Citation: SN Comprehensive Clinical Medicine; Jul 2020; vol. 2 (no. 7); p. 886-892 Author(s): Fratoni E.; dos Santos Nascimento M.V.P.; Bramorski Mohr E.T.; Monguilhott Dalmarco E.; da Silva Fontoura E.; de Moraes Trindade E.B.S. Abstract: Sepsis is a serious disease that affects many people worldwide, and many therapies are used, including corticosteroids such as dexamethasone. However, there is no conclusion as yet, concerning the use of dexamethasone in patients with sepsis or septic shock. The aim of this study was to perform a literature review to assess the mortality of patients with sepsis or septic shock using dexamethasone, answering the following question: What is the effect of dexamethasone on mortality in adult and elderly patients with sepsis compared with mortality in patients who do not use anti-inflammatory therapy? The protocol of this study was registered in the PROSPERO database. The systematic literature search was performed in four electronic databases. Bias risk assessments were performed using the Cochrane Collaboration tool, and notification quality was assessed using the CONSORT-based checklist. The literature search initially identified 13,999 records. The three selected studies included eighty adult patients with sepsis or septic shock who had received dexamethasone as an intervention. Of the three articles, two concluded that the use of dexamethasone significantly reduces the mortality in patients with sepsis or septic shock. The Cochrane Collaboration tool bias risk results showed that none of the studies was completely bias-free and through the CONSORT checklist, it was found that none of the studies met 50% or more of the applicable requirements. Thus, it is clear from this review that further randomized clinical trials comparing the use of dexamethasone to placebo in adjunctive therapy for sepsis patients are needed. The registration number in the PROSPERO database is CRD42018088150.Copyright © 2020, Springer Nature Switzerland AG.

Title: Epidemiology of hospital-onset versus community-onset sepsis in U.S. Hospitals and association with mortality: A retrospective analysis using electronic clinical data Citation: Critical Care MedicineCritical Care Medicine; 2019; vol. 47 (no. 9); p. 1169-1176 Author(s): Rhee C.; Wang R.; Zhang Z.; Klompas M.; Fram D.; Kadri S.S. Objectives: Prior studies have reported that hospital-onset sepsis is associated with higher mortality rates than community-onset sepsis. Most studies, however, have used inconsistent casefinding methods and applied limited risk-adjustment for potential confounders. We used consistent sepsis criteria and detailed electronic clinical data to elucidate the epidemiology and mortality associated with hospital-onset sepsis. Design(s): Retrospective cohort study. Measurements and Main Results: We identified sepsis using Centers for Disease Control and Prevention Adult Sepsis Event criteria and estimated the risk of in-hospital death for hospitalonset sepsis versus community-onset sepsis using logistic regression models. In patients admitted without community-onset sepsis, we estimated risk of death associated with hospital-onset sepsis using Cox regression models with sepsis as a time-varying covariate. Models were adjusted for baseline characteristics and severity of illness. Among 2.2 million hospitalizations, there were 95,154 sepsis cases: 83,620 (87.9%) community-onset sepsis and 11,534 (12.1%) hospital-onset sepsis (0.5% of hospitalized cohort). Compared to community-onset sepsis, hospitalonset sepsis patients were younger (median 66 vs 68 yr) but had more comorbidities (median Elixhauser score 14 vs 11), higher Sequential Organ Failure Assessment scores (median 4 vs 3), higher ICU admission rates (61% vs 44%), longer hospital length of stay (median 19 vs 8 d), and higher in-hospital mortality (33% vs 17%) (p < 0.001 for all comparisons). On multivariate analysis, hospital-onset sepsis was associated with higher mortality versus community-onset sepsis (odds ratio, 2.1; 95% CI, 2.0-2.2) and patients admitted without sepsis (hazard ratio, 3.0; 95% CI, 2.9-3.2). Conclusion(s): Hospital-onset sepsis complicated one in 200 hospitalizations and accounted for one in eight sepsis cases, with one in three patients dying in-hospital. Hospital-onset sepsis preferentially

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afflicted ill patients but even after risk-adjustment, they were twice as likely to die as community-onset sepsis patients; in patients admitted without sepsis, hospital-onset sepsis tripled the risk of death. Hospital-onset sepsis is an important target for surveillance, prevention, and quality improvement initiatives. Copyright © 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Title: Impact of a qSOFA-based triage procedure on antibiotic timing in ED patients with sepsis: A prospective interventional study Citation: American Journal of Emergency MedicineAmerican Journal of Emergency Medicine; Mar 2020; vol. 38 (no. 3); p. 477-484 Author(s): Petit J.; Passerieux J.; Maitre O.; Guerin C.; Rozelle C.; Cordeau O.; Cassonnet A.; Malet A.; Boulain T.; Barbier F.; Bellec C.; Carre V.; Elhadj C.; Delorme N.; Ducroquet P.; Ebrahim L.; Gauffre S.; Giovannetti O.; Guerineau A.; Lacroix M.; Leclerc M.; Leclerc R.; Maillard F.; Mediouni K.; Nabli N.; Pelletier C.; Popescu D.; Stoican L.; Surville J.; Tsegan-Yawo E. Background: It has not been investigated whether the quick sepsis-related organ failure assessment score (qSOFA), a new bedside tool for early sepsis detection, may help accelerating antibiotic initiation in ED patients with sepsis. Method(s): In this prospective pre/post quasi-experimental single-ED study, patients admitted with a suspected bacterial infection were managed using standard triage procedures only (baseline) or in association with qSOFA (intervention, with prioritization of patients with a qSOFA >= 2). Result(s): A total of 151/328 (46.0%) and 185/350 (52.8%) patients with definite bacterial infection met the criteria for sepsis in the baseline and intervention periods, respectively. The sensitivity and specificity of a qSOFA >= 2 for sepsis prediction were 17.3% (95% confidence interval [CI], 13.6%-21.7%) and 98.8% (95% CI, 97.0%-99.5%). Eleven (7.3%) and 28 (13.5%) patients with sepsis in the baseline and intervention periods received a first antibiotic dose within one hour following triage (primary endpoint, absolute difference 6.2%, 95% CI [-0.5%, 12.7%], P = 0.08). The proportions of patients with sepsis receiving a first antibiotic dose within three hours following triage (39.7% [50/151] versus 36.8% [68/185], absolute difference - 2.9%, 95% CI [-13.3%, 7.3%], P = 0.65), requiring ICU admission, or dying in the hospital were similar in both periods. The median ED occupation rate at triage was 104.3% (interquartile range [IQR], 80.4%-128.3%), with a median number of 157 ED visits per day (IQR, 147-169). Conclusion(s): A qSOFA-based triage procedure does not improve antibiotic timing and outcomes in patients with sepsis admitted to a high-volume ED. The qSOFA value at triage was poorly sensitive for early sepsis detection. Trial registration (ClinicalTrials.gov): NCT03299894.Copyright © 2019 Elsevier Inc.

Title: Association of a Care Bundle for Early Sepsis Management with Mortality among Patients with Hospital-Onset or Community-Onset Sepsis Citation: JAMA Internal MedicineJAMA Internal Medicine; May 2020; vol. 180 (no. 5); p. 707-716 Author(s): Baghdadi J.D.; Brook R.H.; Uslan D.Z.; Needleman J.; Cunningham W.E.; Bell D.S.; Wong M.D. Importance: The Early Management Bundle for Severe Sepsis/Septic Shock (SEP-1) is a quality metric based on a care bundle for early sepsis management. Published evidence on the association of SEP-1 with mortality is mixed and largely excludes cases of hospital-onset sepsis. Objective(s): To assess the association of the SEP-1 bundle with mortality and organ dysfunction in cohorts with hospital-onset or community-onset sepsis. Design, Setting, and Participant(s): This retrospective cohort study used data from 4 University of California hospitals from October 1, 2014, to October 1, 2017. Adult inpatients with a diagnosis consistent with sepsis or disseminated infection and laboratory or vital signs meeting the Sepsis-3 (Third International Consensus Definitions for Sepsis and Septic Shock) criteria were divided into

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community-onset sepsis and hospital-onset sepsis cohorts based on whether time 0 of sepsis occurred after arrival in the emergency department or an inpatient area. Data were analyzed from April to October 2019. Additional analyses were performed from December 2019 to January 2020. Exposures: Administration of SEP-1 and 4 individual bundle components (serum lactate level testing, blood culture, broad-spectrum intravenous antibiotic treatment, and intravenous fluid treatment). Main Outcomes and Measures: The primary outcome was in-hospital mortality. The secondary outcome was days requiring vasopressor support, measured as vasopressor days. Result(s): Among the 6404 patient encounters identified (3535 men [55.2%]; mean [SD] age, 64.0 [18.2] years), 2296 patients (35.9%) had hospital-onset sepsis. Among 4108 patients (64.1%) with community-onset sepsis, serum lactate level testing within 3 hours of time 0 was associated with reduced mortality (absolute difference, -7.61%; 95% CI, -14.70% to -0.54%). Blood culture (absolute difference, -1.10 days; 95% CI, -1.85 to -0.34 days) and broad-spectrum intravenous antibiotic treatment (absolute difference, -0.62 days; 95% CI, -1.02 to -0.22 days) were associated with fewer vasopressor days. Among patients with hospital-onset sepsis, broad-spectrum intravenous antibiotic treatment was the only bundle component significantly associated with any improved outcome (mortality difference, -5.20%; 95% CI, -9.84% to -0.56%). Care that was adherent to the complete SEP-1 bundle was associated with increased vasopressor days in patients with community-onset sepsis (absolute difference, 0.31 days; 95% CI, 0.11-0.51 days) but was not significantly associated with reduced mortality in either cohort (absolute difference, -0.07%; 95% CI, -3.02% to 2.88% in community-onset; absolute difference, -0.42%; 95% CI, -6.77% to 5.93% in hospital-onset). Conclusions and Relevance: SEP-1-adherent care was not associated with improved outcomes of sepsis. Although multiple components of SEP-1 were associated with reduced mortality or decreased days of vasopressor therapy for patients who presented with sepsis in the emergency department, only broad-spectrum intravenous antibiotic treatment was associated with reduced mortality when time 0 occurred in an inpatient unit. Current sepsis quality metrics may need refinement. Copyright © 2020 American Medical Association. All rights reserved.

Title: Sepsis and Septic Shock - Basics of diagnosis, pathophysiology and clinical decision making. Citation: The Medical clinics of North America; Jul 2020; vol. 104 (no. 4); p. 573-585 Author(s): Font, Michael D; Thyagarajan, Braghadheeswar; Khanna, Ashish K Abstract: Sepsis and septic shock are major causes of mortality among hospitalized patients. The sepsis state is due to dysregulated host response to infection, leading to inflammatory damage to nearly every organ system. Early recognition of sepsis and appropriate treatment with antibiotics, fluids, and vasopressors is essential to reducing organ system injury and mortality. This review summarizes the current understanding of the epidemiology, pathophysiology, diagnosis, and treatment of sepsis and septic shock.

Title: Challenges in developing a consensus definition of neonatal sepsis. Citation: Pediatric research; Jul 2020; vol. 88 (no. 1); p. 14-26 Author(s): McGovern, Matthew; Giannoni, Eric; Kuester, Helmut; Turner, Mark A; van den Hoogen, Agnes; Bliss, Joseph M; Koenig, Joyce M; Keij, Fleur M; Mazela, Jan; Finnegan, Rebecca; Degtyareva, Marina; Simons, Sinno H P; de Boode, Willem P; Strunk, Tobias; Reiss, Irwin K M; Wynn, James L; Molloy, Eleanor J; Infection, Inflammation, Immunology and Immunisation (I4) section of the ESPR Abstract: Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on

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microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.

Title: Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis. Citation: Intensive care medicine; Jun 2020 Author(s): Markwart, Robby; Saito, Hiroki; Harder, Thomas; Tomczyk, Sara; Cassini, Alessandro; Fleischmann-Struzek, Carolin; Reichert, Felix; Eckmanns, Tim; Allegranzi, Benedetta Purpose: Sepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear. We aimed to summarize the epidemiological evidence related to the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis. Methods: We searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018. We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin. We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed. Results: Of the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries. Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide. The proportion of HA sepsis among all hospital-treated sepsis cases was 23.6% (95% CI 17-31.8%, range 16-36.4%). In the ICU, 24.4% (95% CI 16.7-34.2%, range 10.3-42.5%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 48.7% (95% CI 38.3-59.3%, range 18.7-69.4%) had a hospital origin. The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 9.3 (95% CI 7.3-11.9, range 2-20.6)). In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 56.5 (95% CI 35-90.2, range 9.2-254.4) and it was particularly high in NICUs. Mortality of ICU patients with HA sepsis with organ dysfunction was 52.3% (95% CI 43.4-61.1%, range 30.1-64.6%). There was a significant inter-study heterogeneity. Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies. Conclusion: HA sepsis is of major public health importance, and the burden is particularly high in ICUs. There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients.

Title: Outcome of Immediate Versus Early Antibiotics in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis. Citation: Annals of emergency medicine; Jun 2020 Author(s): Rothrock, Steven G; Cassidy, David D; Barneck, Mitchell; Schinkel, Michiel; Guetschow, Brian; Myburgh, Christiaan; Nguyen, Linh; Earwood, Ryan; Nanayakkara, Prabath W B; Nannan Panday, Rishi S; Briscoe, Joshua G

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Study Objective: Debate exists about the mortality benefit of administering antibiotics within either 1 or 3 hours of sepsis onset. We performed this meta-analysis to analyze the effect of immediate (0 to 1 hour after onset) versus early (1 to 3 hours after onset) antibiotics on mortality in patients with severe sepsis or septic shock. Methods: This review was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searched databases included PubMed, EMBASE, Web of Science, and Cochrane Library, as well as gray literature. Included studies were conducted with consecutive adults with severe sepsis or septic shock who received antibiotics within each period and provided mortality data. Data were extracted by 2 independent reviewers and pooled with random effects. Two authors independently assessed quality of evidence across all studies with Cochrane's Grading of Recommendations Assessment, Development and Evaluation methodology and risk of bias within each study, using the Newcastle-Ottawa Scale. Results: Thirteen studies were included: 5 prospective longitudinal and 8 retrospective cohort ones. Three studies (23%) had a high risk of bias (Newcastle-Ottawa Scale). Overall, quality of evidence across all studies (Grading of Recommendations Assessment, Development and Evaluation) was low. Pooling of data (33,863 subjects) showed no difference in mortality between patients receiving antibiotics in immediate versus early periods (odds ratio 1.09; 95% confidence interval 0.98 to 1.21). Analysis of severe sepsis studies (8,595 subjects) found higher mortality in immediate versus early periods (odds ratio 1.29; 95% confidence interval 1.09 to 1.53). Conclusion: We found no difference in mortality between immediate and early antibiotics across all patients. Although the quality of evidence across studies was low, these findings do not support a mortality benefit for immediate compared with early antibiotics across all patients with sepsis.

Title: Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Citation: Intensive care medicine; Jun 2020 Author(s): Fleischmann-Struzek, C; Mellhammar, L; Rose, N; Cassini, A; Rudd, K E; Schlattmann, P; Allegranzi, B; Reinhart, K Purpose: To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates. Methods: Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes. Results: Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame). Conclusions: Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance.

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Title: Prognostic role of red blood cell distribution width in patients with sepsis: a systematic review and meta-analysis. Citation: BMC immunology; Jul 2020; vol. 21 (no. 1); p. 40 Author(s): Zhang, Lin; Yu, Cui-Hua; Guo, Kuan-Peng; Huang, Cai-Zhi; Mo, Li-Ya Background: Outcome prediction for patients with sepsis may be conductive to early aggressive interventions. Numerous biomarkers and multiple scoring systems have been utilized in predicting outcomes, however, these tools were either expensive or inconvenient. We performed a meta-analysis to evaluate the prognostic role of red blood cell distribution width (RDW) in patients with sepsis. Methods: The online databases of Embase, Web of science, Pubmed, Corchrane library, Chinese Wanfang database, CNKI database were systematically searched from the inception dates to June, 24th, 2020, using the keywords red cell distribution width and sepsis. The odds ratio (OR) or Hazards ratio (HR) with corresponding 95% confidence intervals (95%CI) were pooled to evaluate the association between baseline RDW and sepsis. A random-effects model was used to pool the data, and statistical heterogeneity between studies was evaluated using the I2 statistic. Sensitivity and subgroup analyses were performed to detect the publication bias and origin of heterogeneity. Results: Eleven studies with 17,961 patients with sepsis were included in the meta-analysis. The pooled analyses indicated that increased baseline RDW was associated with mortality (HR = 1.14, 95%CI 1.09-1.20, Z = 5.78, P < 0.001) with significant heterogeneity (I2 = 80%, Pheterogeneity < 0.001). Similar results were found in the subgroup analysis stratified by site of infection, comorbidity, Newcastle-Ottawa Scale (NOS) score, study design, patients' country. The predefined subgroup analysis showed that NOS score may be the origin of heterogeneity. Conclusions: For patients with sepsis, baseline RDW may be a useful predictor of mortality, patients with increased RDW are more likely to have higher mortality.

Title: Antibiotic treatment in patients with sepsis: a narrative review. Citation: Hospital practice (1995); Jul 2020 Author(s): Plata, Erika; Ferrer, Ricard; Ruiz Rodríguez, Juan Carlos; Morais, Rui; Póvoa, Pedro Abstract: Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, with unacceptably high morbidity and mortality. Similar to acute myocardial infarction or cerebral vascular accident, sepsis is a severe and continuous time-dependent condition. Thus, in the case of sepsis, early and adequate administration of antimicrobials must be a priority, ideally within the first hour of diagnosis, simultaneously with organ support. As a consequence of the emergence of multidrug-resistant pathogens, the choice of antimicrobials should be performed according to the local pathogen patterns of resistance. Individual antimicrobial optimization is essential to achieve adequate concentrations of antimicrobials, to reduce adverse effects, and to ensure successful outcomes, as well as preventing the emergence of multidrug-resistant pathogens. The loading dose is the administration of an initial higher dose of antimicrobials, regardless of the presence of organ dysfunction. Further doses should be implemented according to pharmacokinetics/pharmacodynamics of antimicrobials and should be adjusted according to the presence of renal or liver dysfunction. Extended or continuous infusion of beta-lactams and therapeutic drug monitoring can help to achieve therapeutic levels of antimicrobials. Duration and adequacy of treatment must be reviewed at regular intervals to allow effective de-escalation and administration of short courses of antimicrobials for most patients. Antimicrobial stewardship frameworks, leadership, focus on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches will help us to improve patients the process of care and overall quality of care.

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Title: Time to positive blood culture in early onset neonatal sepsis: A retrospective clinical study and review of the literature. Citation: Journal of paediatrics and child health; Jul 2020 Author(s): Marks, Lucinda; de Waal, Koert; Ferguson, John K Aim: Neonatal early onset sepsis (EOS) is a low-incidence, high-risk disease which has prompted significant overtreatment with antibiotics for the standard duration of 48 h. The aims of this study were to determine whether blood cultures collected from term and late preterm neonates for EOS would return a positive result for pathogenic bacteria within 24 h and to review the literature to supplement the results. Methods: This is a retrospective observational study of time to positive blood culture in the BACTEC culture system from neonates ≥34 weeks in a single referral centre between 1999 and 2018. A literature review was conducted through PubMed, MEDLINE and Embase using search terms of 'neonatal sepsis' AND 'blood culture'. Studies were included if they reported time to positive blood culture in EOS. Results: Forty positive cultures were included in this report, with 39 (98%) showing bacterial growth within 24 h. One culture, obtained after commencement of antibiotics, became positive at 3 days. Sixteen papers were included in our literature review and six presented data for an EOS cohort; a median of 96.5% of pathogenic EOS blood cultures become positive within 24 h. Conclusions: All pathogenic blood cultures collected pre-therapy from neonates ≥34 weeks suspected of EOS returned a positive result within 24 h of incubation. Similar studies have found that 92-100% of cultures are positive by 24 h. This data could contribute to re-evaluation of the current standard duration of antibiotic use in term and late preterm neonates with suspected EOS.

Title: Sepsis after elective neurosurgery: Incidence, outcomes, and predictive factors. Citation: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia; Jul 2020 Author(s): Pertsch, Nathan J; Tang, Oliver Y; Seicean, Andreea; Toms, Steven A; Weil, Robert J Abstract: Sepsis is a life-threatening condition resulting from systemic infection, with mortality rates approaching 30%. Most neurological surgeries are now performed electively, which permits medical optimization preoperatively. We performed a retrospective cohort analysis of 122,466 adult elective neurosurgical patients from 2012 to 2018 in the National Surgical Quality Improvement Program database. To select for a medically optimized population, patients were included if they arrived from home on the day of surgery, were not pregnant or puerperium, and had no documented evidence of preexisting infection. We analyzed demographic, comorbidity, and operative information; performed multivariate logistic regression to explore factors predictive of postoperative sepsis; and evaluated outcomes for patients who developed sepsis. Overall, 0.87% of patients developed postoperative sepsis (n = 1,067). The rate of sepsis was higher in the cranial subpopulation (1.21%; n = 330) and lower in the spinal subpopulation (0.77%; n = 733). The overall sepsis cohort was older, had more males, was more functionally dependent, had longer operation durations, and had higher rates of medical comorbidities. Minority race and smoking were not associated with sepsis. The sepsis cohort fared worse than the control cohort across all outcome measures, including prolonged length-of-stay (≥90th percentile), discharge anywhere but home, 30-day readmission, 30-day reoperation, and 30-day mortality. Results for the cranial and spine subpopulations follow similar trends. In summary, sepsis in the elective neurosurgical population is an uncommon but devastating cause of excess morbidity and mortality.

Title: Vitamin C and thiamine are associated with lower mortality in sepsis. Citation: The journal of trauma and acute care surgery; Jul 2020; vol. 89 (no. 1); p. 111-117

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Author(s): Byerly, Saskya; Parreco, Joshua P; Soe-Lin, Hahn; Parks, Jonathan J; Lee, Eugenia E; Shnaydman, Ilya; Mantero, Alejandro; Yeh, D Dante; Namias, Nicholas; Rattan, Rishi Background: The efficacy of vitamin C (VitC) and thiamine (THMN) in patients admitted to the intensive care unit (ICU) with sepsis is unclear. The purpose of this study was to evaluate the effect of VitC and THMN on mortality and lactate clearance in ICU patients. We hypothesized that survival and lactate clearance would be improved when treated with thiamine and/or VitC. Methods: The Philips eICU database version 2.0 was queried for patients admitted to the ICU in 2014 to 2015 for 48 hours or longer and patients with sepsis and an elevated lactate of 2.0 mmol/L or greater. Subjects were categorized according to the receipt of VitC, THMN, both, or neither. The primary outcome was in-hospital mortality. Secondary outcome was lactate clearance defined as lactate less than 2.0 mmol/L achieved after maximum lactate. Univariable comparisons included age, sex, race, Acute Physiology Score III, Acute Physiology and Chronic Health Evaluation (APACHE) IVa score, Sequential Organ Failure Assessment, surgical ICU admission status, intubation status, hospital region, liver disease, vasopressors, steroids, VitC and THMN orders. Kaplan-Meier curves, logistic regression, propensity score matching, and competing risks modeling were constructed. Results: Of 146,687 patients from 186 hospitals, 7.7% (n = 11,330) were included. Overall mortality was 25.9% (n = 2,930). Evidence in favor of an association between VitC and/or THMN administration, and survival was found on log rank test (all p < 0.001). After controlling for confounding factors, VitC (adjusted odds ratio [AOR], 0.69 [0.50-0.95]) and THMN (AOR, 0.71 [0.55-0.93]) were independently associated with survival and THMN was associated with lactate clearance (AOR, 1.50 [1.22-1.96]). On competing risk model VitC (AOR, 0.675 [0.463-0.983]), THMN (AOR, 0.744 [0.569-0.974]), and VitC+THMN (AOR, 0.335 [0.13-0.865]) were associated with survival but not lactate clearance. For subgroup analysis of patients on vasopressors, VitC+THMN were associated with lactate clearance (AOR, 1.85 [1.05-3.24]) and survival (AOR, 0.223 [0.0678-0.735]). Conclusion: VitC+THMN is associated with increased survival in septic ICU patients. Randomized, multicenter trials are needed to better understand their effects on outcomes. Level Of Evidence: Therapeutic Study, Level IV.

Title: Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy: A systematic review and meta-analysis. Citation: Journal of thrombosis and haemostasis : JTH; Jul 2020; vol. 18 (no. 7); p. 1618-1625 Author(s): Valeriani, Emanuele; Squizzato, Alessandro; Gallo, Andrea; Porreca, Ettore; Vincent, Jean-Louis; Iba, Toshiaki; Hagiwara, Akiyoshi; Di Nisio, Marcello Background: The efficacy and safety of recombinant human soluble thrombomodulin (rhsTM) have not been definitively proven. The effects may depend on the presence of sepsis-associated coagulopathy (SAC). Objectives: The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of rhsTM in patients with SAC defined by high international normalized ratio and low platelet count. Patients/Methods: EMBASE, MEDLINE, CENTRAL, and clinicaltrial.gov were searched for randomized controlled trials (RCTs) comparing rhsTM with placebo or no treatment in patients with sepsis. The efficacy outcome was 28-day mortality, and the safety outcome was major bleeding. Results: We included 3 RCTs with a total of 1633 patients. Twenty-eight-day mortality was higher in patients with SAC compared with those without SAC (risk ratio [RR] 1.32; 95% confidence intervals [CI], 1.06-1.64). rhsTM was associated with significantly lower 28-day mortality compared with placebo or no treatment in patients with SAC (RR 0.80; 95% CI, 0.65-0.98), but not in those without SAC (RR 1.17; 95% CI, 0.82-1.67) nor in the whole study population (RR 0.88; 95% CI, 0.74-1.04). There was no significant difference in major bleeding between rhsTM and controls in the whole population (RR 1.25; 95% CI, 0.80-1.96), patients with SAC (RR 0.94; 95% CI, 0.45-1.95), and those without SAC (RR 2.26; 95% CI, 0.95-5.35).

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Conclusions: In patients with sepsis, SAC is associated with higher 28-day mortality. The administration of rhsTM reduced 28-day mortality in patients with SAC, but not in those without SAC.

Title: Mediating Effects of Frailty Indicators on the Risk of Sepsis After Cancer. Citation: Journal of intensive care medicine; Jul 2020; vol. 35 (no. 7); p. 708-719 Author(s): Moore, Justin Xavier; Akinyemiju, Tomi; Bartolucci, Alfred; Wang, Henry E; Waterbor, John; Griffin, Russell Background: Cancer survivors are at increased risk of sepsis, possibly attributed to weakened physiologic conditions. The aims of this study were to examine the mediation effect of indicators of frailty on the association between cancer survivorship and sepsis incidence and whether these differences varied by race. Methods: We performed a prospective analysis using data from the REasons for Geographic and Racial Differences in Stroke cohort from years 2003 to 2012. We categorized frailty as the presence of ≥2 frailty components (weakness, exhaustion, and low physical activity). We categorized participants as "cancer survivors" or "no cancer history" derived from self-reported responses of being diagnosed with any cancer. We examined the mediation effect of frailty on the association between cancer survivorship and sepsis incidence using Cox regression. We repeated analysis stratified by race. Results: Among 28 062 eligible participants, 2773 (9.88%) were cancer survivors and 25 289 (90.03%) were no cancer history participants. Among a total 1315 sepsis cases, cancer survivors were more likely to develop sepsis (12.66% vs 3.81%, P < .01) when compared to participants with no cancer history (hazard ratios: 2.62, 95% confidence interval: 2.31-2.98, P < .01). The mediation effects of frailty on the log-hazard scale were very small: weakness (0.57%), exhaustion (0.31%), low physical activity (0.20%), frailty (0.75%), and total number of frailty indicators (0.69%). Similar results were observed when stratified by race. Conclusion: Cancer survivors had more than a 2-fold increased risk of sepsis, and indicators of frailty contributed to less than 1% of this disparity.

Title: Assessment of Health Care Exposures and Outcomes in Adult Patients With Sepsis and Septic Shock. Citation: JAMA network open; Jul 2020; vol. 3 (no. 7); p. e206004 Author(s): Fay, Katherine; Sapiano, Mathew R P; Gokhale, Runa; Dantes, Raymund; Thompson, Nicola; Katz, David E; Ray, Susan M; Wilson, Lucy E; Perlmutter, Rebecca; Nadle, Joelle; Godine, Deborah; Frank, Linda; Brousseau, Geoff; Johnston, Helen; Bamberg, Wendy; Dumyati, Ghinwa; Nelson, Deborah; Lynfield, Ruth; DeSilva, Malini; Kainer, Marion; Zhang, Alexia; Ocampo, Valerie; Samper, Monika; Pierce, Rebecca; Irizarry, Lourdes; Sievers, Marla; Maloney, Meghan; Fiore, Anthony; Magill, Shelley S; Epstein, Lauren Importance: Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data. Objective: To describe sepsis epidemiology in adults. Design, Setting, and Participants: This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge

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diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019. Main Outcomes and Measures: The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed. Results: Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality. Conclusions and Relevance: Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.

Title: Epidemiology and patient predictors of infection and sepsis in the prehospital setting. Citation: Intensive care medicine; Jul 2020; vol. 46 (no. 7); p. 1394-1403 Author(s): Lane, Daniel J; Wunsch, Hannah; Saskin, Refik; Cheskes, Sheldon; Lin, Steve; Morrison, Laurie J; Oleynick, Christopher J; Scales, Damon C Purpose: Paramedics are often the first healthcare contact for patients with infection and sepsis and may identify them earlier with improved knowledge of the clinical signs and symptoms that identify patients at higher risk. Methods: A 1-year (April 2015 and March 2016) cohort of all adult patients transported by EMS in the province of Alberta, Canada, was linked to hospital administrative databases. The main outcomes were infection, or sepsis diagnosis among patients with infection, in the Emergency Department. We estimated the probability of these outcomes, conditional on signs and symptoms that are commonly available to paramedics. Results: Among 131,745 patients transported by EMS, the prevalence of infection was 9.7% and sepsis was 2.1%. The in-hospital mortality rate for patients with sepsis was 28%. The majority (62%) of patients with infections were classified by one of three dispatch categories ("breathing problems," "sick patient," or "inter-facility transfer"), and the probability of infection diagnosis was 17-20% for patients within these categories. Patients with elevated temperature measurements had the highest probability for infection diagnosis, but altered Glasgow Coma Scale (GCS), low blood pressure, or abnormal respiratory rate had the highest probability for sepsis diagnosis. Conclusion: Dispatch categories and elevated temperature identify patients with higher probability of infection, but abnormal GCS, low blood pressure, and abnormal respiratory rate identify patients with infection who have a higher probability of sepsis. These characteristics may be considered by paramedics to identify higher-risk patients prior to arrival at the hospital.

Title: Sepsis: A Review for Home Healthcare Clinicians. Citation: Home healthcare now; ; vol. 38 (no. 4); p. 188-192 Author(s): Durning, Marijke Vroomen

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Abstract: Sepsis is a life-threatening response to infection that affects over 1.7 million people annually in the United States. Although sepsis can strike healthy and active people of all ages, those at highest risk are older adults, infants, and people with chronic illnesses or an impaired immune system. Many people who had sepsis recover and resume life as it was before. However, others require some level of postdischarge home healthcare. Up to 60% of survivors, particularly of severe sepsis and septic shock, are left with cognitive and/or physical limitations. About one-third of all sepsis survivors and more than 40% of older survivors are rehospitalized within 3 months of the initial sepsis diagnosis, most commonly due to a repeat episode of sepsis or another infection. Quality home healthcare follow-up of sepsis patients is paramount in lowering readmission rates, preventing reoccurrence of sepsis, and assisting patients and families during the postsepsis phase of healthcare.

Title: The renal safety of a single dose of gentamicin in patients with sepsis in the emergency department. Citation: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases; Jul 2020 Author(s): Cobussen, Maarten; Haeseker, Michiel B; Stoffers, Judith; Wanrooij, Vera H M; Savelkoul, Paul H M; Stassen, Patricia M Objectives: To determine the effect of a single-dose of gentamicin on the incidence and persistence of acute kidney injury (AKI) in patients with sepsis in the emergency department (ED). Methods: We retrospectively enrolled patients with sepsis in the ED in three hospitals. Local antibiotic guidelines recommended a single-dose of gentamicin as part of empirical therapy in selected patients in one hospital, whereas the other two hospitals did not. Multivariate analysis was used to evaluate the effect of gentamicin and other potential risk factors on the incidence and persistence of AKI after admission. AKI was defined according to the KDIGO criteria. Results: Of 1573 patients, 571/1573 (32.9%) received a single-dose of gentamicin. At admission, 181/571 (31.7%) of the gentamicin and 228/1002 (22.8%) of the non-gentamicin patients had AKI (p<0.001). After admission, AKI occurred in 64/571 (12.0%) of the gentamicin and in 82/1002 (8.9%) of the control group (p=0.06). Multivariate analysis showed that shock (OR 2.72 (95%CI, 1.31-5.67)), diabetes mellitus (OR 1.49 (95%CI, 1.001 - 2.23)), and higher baseline (i.e. pre-admission) serum creatinine (OR 1.007 (95%CI, 1.005-1.009)) were associated with the development of AKI after admission, but not gentamicin (OR 1.29 (95%CI, 0.89-1.86)). Persistent AKI was rare in both the gentamicin (16/260 (6.2%)) and the non-gentamicin group (15/454 (3.3%), p=0.09). Conclusions: Our study shows that a single-dose of gentamicin in patients with sepsis in the ED is safe with regard to renal function. The development of AKI after admission was associated with shock, diabetes mellitus, and a higher baseline creatinine.

Title: Corticosteroids in the Treatment of Sepsis. Citation: Academic emergency medicine : official journal of the Society for Academic Emergency Medicine; Jun 2020 Author(s): Allen, Robert; Tepler, Peter Abstract: The review summarized here by Annane et al found that corticosteroids may confer a short-term, but not overall, mortality benefit for patients with sepsis. Specifically, they found moderate certainty evidence for reduced 28-day mortality (relative risk [RR] 0.91, 95% confidence interval [CI] 0.84 to 0.99; n=11233).

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Title: Venoarterial Extracorporeal Membranous Oxygenation: Treatment Option for Sepsis-Induced Cardiogenic Shock? A Systematic Review. Citation: Critical care medicine; Jun 2020 Author(s): Sato, Ryota; Kuriyama, Akira Objectives: Clinicians often encounter adult patients with septic shock who fail to respond to fluid therapy and vasopressors. There is an increasing interest in venoarterial extracorporeal membranous oxygenation in the treatment of patients with septic shock, but its outcomes and safety remain unclear. The aim of this study is to describe in-hospital mortality and complication rate in adult patients with septic shock who underwent venoarterial extracorporeal membranous oxygenation, and to identify patients who may potentially benefit from venoarterial extracorporeal membranous oxygenation. Data Sources: The protocol for this systematic review was registered at International Prospective Register of Systematic Reviews (CRD42018098848). We searched MEDLINE, Embase, and Igaku Chuo Zasshi for studies of any design in which patients with septic shock were treated with venoarterial extracorporeal membranous oxygenation. Our search was updated on October 6, 2019. Study Selection: Two independent reviewers assessed whether titles and abstracts met the eligibility criteria. Studies were included when patients met the following criteria: 1) age 18 years old or older; 2) septic shock; and 3) treated with venoarterial extracorporeal membranous oxygenation as hemodynamic support. When there were disagreements between reviewers, the full text was reviewed, and discussion was continued until a consensus was reached. Data Extraction: Two authors independently extracted the selected patient and study characteristics and outcomes. Data Synthesis: A total of 6,457 studies were screened. Six retrospective studies were included. The in-hospital mortality rate of patients with septic shock who underwent venoarterial extracorporeal membranous oxygenation was 76.7% (188/245). Four studies provided cardiac function with left ventricular ejection fraction and/or cardiac index. In two of these four studies where median left ventricular ejection fraction and cardiac index were 16.0% and 1.3 L/min/m and median left ventricular ejection fraction and mean cardiac index were 30.0% and 2.4 L/min/m, respectively, the in-hospital mortalities were markedly lower (14.8% and 28.6%, respectively) than the other two studies (78.1% and 91.5%, respectively) that included populations with median left ventricular ejection fraction of 25.0% and mean cardiac index of 2.1 L/min/m. Complications were reported in five studies (39 events/174 cases), hemorrhage (22 events/174 cases) being the most common. Conclusions: Venoarterial extracorporeal membranous oxygenation remains a controversial treatment strategy in septic shock. The reported in-hospital mortality rates in patients with sepsis-induced cardiogenic shock who underwent venoarterial extracorporeal membranous oxygenation were quite inconsistent. There is a need for well-designed studies to assess the benefit and safety of venoarterial extracorporeal membranous oxygenation in patients with sepsis-induced cardiogenic shock.

Title: Effect of IV Push Antibiotic Administration on Antibiotic Therapy Delays in Sepsis. Citation: Critical care medicine; Jun 2020 Author(s): Gregorowicz, Alex J; Costello, Patrick G; Gajdosik, David A; Purakal, John; Pettit, Natasha N; Bastow, Samantha; Ward, Michael A Objectives: Timeliness of antibiotic administration is recognized as an important factor in reducing mortality associated with sepsis. According to guidelines, antibiotics should be administered within 1 hour of sepsis presentation and the Centers for Medicare & Medicaid Services mandates administration within 3 hours. This study evaluates the difference in time from sepsis diagnosis to first-dose completion of β-lactam antibiotics between IV push and IV piggyback administration. Design: Single-center, retrospective analysis.

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Setting: Urban, tertiary-care emergency department. Patients: Inclusion criteria were as follows: 1) adult patients (n = 274) diagnosed with severe sepsis or septic shock per Sepsis-2 criteria from September to November 2016 and from September to November 2017 and 2) received β-lactam antibiotic. Interventions: Initial β-lactam agent administered as either IV push or IV piggyback. Measurements and Main Results: Median time (interquartile range) from sepsis diagnosis to administration of a β-lactam antibiotic was 48 minutes (19-96 min) versus 72 minutes (8-180 min) and to administration of the complete broad-spectrum regimen was 108 minutes (66-144 min) versus 114 minutes (42-282 min) in the IV push (n = 143) versus IV piggyback (n = 131) groups, respectively. When controlling for time to sepsis diagnosis and other factors, IV push was associated with approximately 32-minute time savings to β-lactam (β = -0.60; 95% CI, -0.91 to -0.29) and approximately 32-minute time savings to broad-spectrum (β = -0.32; 95% CI, -0.62 to -0.02) antibiotic administrations. The IV push group was less likely to fail the goal of β-lactam antibiotics within 1 hour (44.6% vs 57.3%; odds ratio, 2.27; 95% CI, 1.34-3.86) and 3 hours (7.6% vs 24.5%; odds ratio, 4.31; 95% CI, 2.01-10.28) of sepsis diagnosis compared with IV piggyback. The IV push strategy did not affect mortality, need for ICU admission, or ICU length of stay. No adverse events, including infusion reactions, were found in either arm. Conclusions: Use of an IV push strategy may safely facilitate more rapid administration of β-lactam antibiotics and may allow for better compliance with sepsis management guidelines.

Sources Used: The following databases are used in the creation of this bulletin: BNI, CINAHL, EMBASE & Medline. Disclaimer: The results of your literature search are based on the request that you made, and consist of a list of references, some with abstracts. Royal United Hospital Bath Healthcare Library will endeavour to use the best, most appropriate and most recent sources available to it, but accepts no liability for the information retrieved, which is subject to the content and accuracy of databases, and the limitations of the search process. The library assumes no liability for the interpretation or application of these results, which are not intended to provide advice or recommendations on patient care