Sepsis-related Deaths Research Articles

Epigenetic and metabolic programming of innate immunity in sepsis.

Sepsis, the 10th leading cause of death, is the most expensive condition in the United States. The immune response in sepsis transitions from hyperinflammatory to a hypoinflammatory and immunosuppressive phase; individual variations regarding timing and overlap between hyper- and hypoinflammation exist in a number of patients. While one third of the sepsis-related deaths occur during hyperinflammation, majority of the sepsis-mortality occurs during the hypoinflammatory phase. Currently, no phase-specific molecular-based therapies exist to treat sepsis. Coordinated epigenetic and metabolic perturbations orchestrate this shift from hyper- to hypoinflammation in innate immune cells during sepsis. These epigenetic and metabolic changes during sepsis progression and therapeutic opportunities they pose are described in this review.

A Large Proportion of Hospital Deaths Are Due to Sepsis

To better understand sepsis-related deaths at six U.S. hospitals (3 tertiary care, 3 community hospitals), investigators reviewed the records of 568

PP88 Economic Impact Of New Diagnostic Tools In Severe Sepsis

IntroductionConstantly rising healthcare costs and the increasing incidence of antimicrobial resistance represent a growing burden on public health, affecting patients, physicians, payers, and health authorities. This analysis assessed the economic impact of improved diagnostic accuracy among septic patients.MethodsA cost-consequence model was developed to evaluate two different scenarios for the treatment of severe sepsis: scenario one represents the current status of diagnostic performance used for an antimicrobial treatment; scenario two is based on the assumption that a more accelerated diagnostic process results in 15 percent more patients being treated with an efficient antimicrobial drug early in their therapy. Data for the average patient-related cost for diagnostics (EUR 1,182) and overall cost (EUR 12,090), length of hospital stay (average 18.7 days), and number of patients affected annually (n = 771) were derived from the German Diagnosis-Related Group Catalog for 2017. Further, the impact of optimal versus inadequate therapeutic approaches on length of hospital stay (38% decrease), hospitalization cost (40% decrease), and mortality rate (28% decrease) were derived from published sources.ResultsBy using more efficient tests to enable earlier detection of sepsis in patients who otherwise would not receive appropriate treatment, 36 additional patients were appropriately treated. The overall annual length of hospital stay can be shortened by 319 days and the number of sepsis-related deaths reduced by three. The overall annual costs in scenarios 1 and 2 amounted to EUR 11.4 and EUR 11.2 million, respectively. The main savings resulted from reduced expenses for hospital stay, drugs, readmissions, and progression to septic shock.ConclusionsIncreasing cost pressure and the rise in multi-resistant germs are a burden, which will increase over the next decade. The present analysis showed that a willingness to intervene early and stop detrimental developments, and to invest in effective technologies, can promote affordable health care.

Red-flag sepsis and SOFA identifies different patient population at risk of sepsis-related deaths on the general ward.

Controversy exists regarding the best diagnostic and screening tool for sepsis outside the intensive care unit (ICU). Sequential organ failure assessment (SOFA) score has been shown to be superior to systemic inflammatory response syndrome (SIRS) criteria, however, the performance of "Red Flag sepsis criteria" has not been tested formally.The aim of the study was to investigate the ability of Red Flag sepsis criteria to identify the patients at high risk of sepsis-related death in comparison to SOFA based sepsis criteria. We also investigated the comparison of Red Flag sepsis to quick SOFA (qSOFA), SIRS, and national early warning score (NEWS) scores and factors influencing patient mortality.Patients were recruited into a 24-hour point-prevalence study on the general wards and emergency departments across all Welsh acute hospitals. Inclusion criteria were: clinical suspicion of infection and NEWS 3 or above in-line with established escalation criteria in Wales. Data on Red Flag sepsis and SOFA criteria was collected together with qSOFA and SIRS scores and 90-day mortality.459 patients were recruited over a 24-hour period. 246 were positive for Red Flag sepsis, mortality 33.7% (83/246); 241 for SOFA based sepsis criteria, mortality 39.4% (95/241); 54 for qSOFA, mortality 57.4% (31/54), and 268 for SIRS, mortality 33.6% (90/268). 55 patients were not picked up by any criteria. We found that older age was associated with death with OR (95% CI) of 1.03 (1.02-1.04); higher frailty score 1.24 (1.11-1.40); DNA-CPR order 1.74 (1.14-2.65); ceiling of care 1.55 (1.02-2.33); and SOFA score of 2 and above 1.69 (1.16-2.47).The different clinical tools captured different subsets of the at-risk population, with similar sensitivity. SOFA score 2 or above was independently associated with increased risk of death at 90 days. The sequalae of infection-related organ dysfunction cannot be reliably captured based on routine clinical and physiological parameters alone.

The most common causative bacteria in maternal sepsis-related deaths in Japan were group A Streptococcus: A nationwide survey

The present retrospective study provides an in-depth analysis of the maternal sepsis-related deaths reported in Japan, and aims to guide future care regarding maternal sepsis. This is a nationwide, retrospective, descriptive cohort study. Data were retrospectively analyzed on all maternal death cases related to sepsis reported in Japan from 2010 through 2016. A total of 7,347,727 births and 317 maternal deaths were reported during the study period. The cause of maternal death was sepsis in 24 women (7.5%). Causative bacteria were Streptococcus pyogenes (54.2%), Chlamydia psittaci (8.3%), Mycobacterium tuberculosis (8.3%), Escherichia coli (4.2%), Neisseria meningitidis (4.2%), Epstein-Barr virus (4.2%), and unknown (16.6%). In maternal death due to S.pyogenes (13 women), onset periods ware antepartum in 10 women (76.9%) and postpartum in 3 (23.1%); death within 24h after hospital admission occurred in 7 women (53.8%); and the median time from hospital admission to death was 12h (6-744h). The most common causative bacteria in to maternal sepsis-related death were GAS. When encountering severe sepsis during the peripartum period, we recommend considering severe GAS infection and early intervention.

Sirtuins and Immuno-Metabolism of Sepsis.

Sepsis and septic shock are the leading causes of death in non-coronary intensive care units worldwide. During sepsis-associated immune dysfunction, the early/hyper-inflammatory phase transitions to a late/hypo-inflammatory phase as sepsis progresses. The majority of sepsis-related deaths occur during the hypo-inflammatory phase. There are no phase-specific therapies currently available for clinical use in sepsis. Metabolic rewiring directs the transition from hyper-inflammatory to hypo-inflammatory immune responses to protect homeostasis during sepsis inflammation, but the mechanisms underlying this immuno-metabolic network are unclear. Here, we review the roles of NAD+ sensing Sirtuin (SIRT) family members in controlling immunometabolic rewiring during the acute systemic inflammatory response associated with sepsis. We discuss individual contributions among family members SIRT 1, 2, 3, 4 and 6 in regulating the metabolic switch between carbohydrate-fueled hyper-inflammation to lipid-fueled hypo-inflammation. We further highlight the role of SIRT1 and SIRT2 as potential “druggable” targets for promoting immunometabolic homeostasis and increasing sepsis survival.

The golden hour of sepsis: An in-depth analysis of sepsis-related maternal mortality in middle-income country Suriname.

BackgroundSepsis was the main cause of maternal mortality in Suriname, a middle-income country. Objective of this study was to perform a qualitative analysis of the clinical and management aspects of sepsis-related maternal deaths with a focus on the ‘golden hour’ principle of antibiotic therapy.MethodsA nationwide reproductive age mortality survey was performed from 2010 to 2014 to identify and audit all maternal deaths in Suriname. All sepsis-related deaths were reviewed by a local expert committee to assess socio-demographic characteristics, clinical aspects and substandard care.ResultsOf all 65 maternal deaths in Suriname 29 (45%) were sepsis-related. These women were mostly of low socio-economic class (n = 23, 82%), of Maroon ethnicity (n = 14, 48%) and most deaths occurred postpartum (n = 21, 72%). Underlying causes were pneumonia (n = 14, 48%), wound infections (n = 3, 10%) and endometritis (n = 3, 10%). Bacterial growth was detected in 10 (50%) of the 20 available blood cultures. None of the women with sepsis as underlying cause of death received antibiotic treatment within the first hour, although most women fulfilled the diagnostic criteria of sepsis upon admission. In 27 (93%) of the 29 women from which sufficient information was available, substandard care factors were identified: delay in monitoring in 16 (59%) women, in diagnosis in 17 (63%) and in treatment in 21 (78%).ConclusionIn Suriname, a middle-income country, maternal mortality could be reduced by improving early recognition and timely diagnosis of sepsis, vital signs monitoring and immediate antibiotic infusion (within the golden hour).

Sepsis-related mortality in China: a descriptive analysis.

A population-level description and analysis of sepsis-related mortality in China is key to the planning and assessment of interventional strategies. Retrospective analysis of multiple cause of death (MCOD) recorded in the population-based national mortality surveillance system (NMSS) of China. All sepsis-related deaths occurring in 605 disease surveillance points (DSPs) covering 323.8 million population across China were included in our study. Age-standardized mortality and national estimate of sepsis-related deaths were estimated using the census population in 2010 and 2015, respectively. In 2015, a total of 1,937,299 deaths occurring in any of the 605 DSPs and standardized sepsis-related mortality rate was 66.7 (95% confidence interval [CI] 66.4-67.0) deaths per 100,000 population. This produced a national estimate of 1,025,997 sepsis-related deaths. Sepsis-related mortality rates exhibited significant geographic variation. In multilevel analysis, male sex (rate ratio [RR] 1.582, 95% CI 1.570-1.595), increasing age (RR 1.914 for 5-year group, 95% CI 1.910-1.917), and presence of comorbidity (RR 2.316, 95% CI 2.298-2.335) were independently associated with increased sepsis-related mortality. Higher disposable income (RR 0.717 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.515-0.978) and mean years of education (RR 0.808 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.684-0.955) were negatively associated with sepsis-related mortality. However, population-based hospital doctors were not significantly associated with sepsis-related mortality. The standardized sepsis-related mortality rate in China was high and varied according to socioeconomic indices, even though some uncertainty remained.

Analysis on sarcoglycans expression as markers of septic cardiomyopathy in sepsis-related death.

The post-mortem assessment of sepsis-related death can be carry out by many methods recently suggested as microbiological and biochemical investigations. In these cases, the cause of death is a multiple organ dysfunction due to a dysregulated inflammatory response occurring after the failure of infection control process. It was highlighted also that the heart can be a target organ in sepsis which determines the so-called septic cardiomyopathy characterized by myocardial depression. Several mechanisms to explain the pathophysiology of septic cardiomyopathy were suggested, but very few studies about the structural alterations of cardiac cells responsible for myocardial depression were carried out. The aim of this study was to evaluate whether sarcoglycans (SG) were involved in septic cardiac damage analyzing their expression in sepsis-related deaths and, particularly, if these proteins can be used as markers of septic myocardial dysfunction. Cases of septic-related death confirmed by clinical and autopsy records were investigated and compared to a control group of traumatic deaths. Indirect immunofluorescence analysis was performed to analyze α-SG, β-SG, δ-SG, ζ-SG, ε-SG, and γ-SG. Decrease of fluorescence staining pattern for all tested sarcoglycans was observed in the septic-related deaths compared to normal fluorescence staining pattern of control group. These results provide new findings about the myocytes structural alterations due to sepsis and suggest that these proteins could be used in forensic assessment of septic cardiomyopathy.

Mortality trends in a tertiary care hospital in Mysore

AIM: The aim of this study is to find out the various causes of mortality in a tertiary care hospital over a 1-year period. MATERIALS AND METHODS: All deaths occurring in the study period were retrospectively analyzed by analyzing the hospital records from the Medical Records Department for causes of death and various epidemiological parameters such as age and sex. RESULTS: A total of 1028 deaths were included the study. Deaths were more in males than females. More deaths were observed in the fifth and sixth decades of life. The maximum deaths, i.e., 356 were due to sepsis (34.6%) of which pneumonia was the cause in a majority of sepsis-related deaths (36.51%). Cardiovascular causes of death were 184 (17.89%) of which a majority of 130 (70.65%) were related to ischemic heart disease. The other causes of deaths included 137 (13.3%) from road traffic accidents, 117 (11.3%) due to cerebrovascular accidents, 73 (7.1%) due to gastrointestinal tract-related causes, 58 (5.64%) due to primary renal diseases, 45 (4.37%) from chronic respiratory ailments, 32 (3.11%) due to malignancies, 18 (1.75%) due to poisonings, and 4 (0.38%) deaths due to hematological disorders. CONCLUSION: The most common cause of overall mortality was sepsis followed by cardiac causes. Road traffic accidents also significantly contributed to the overall mortality. Steps are needed to be taken to educate the medical fraternity and the people about the prevalence and preventive strategies for communicable and noncommunicable diseases.

Rapid Protective Effects of Early BCG on Neonatal Mortality Among Low Birth Weight Boys: Observations From Randomized Trials.

Three randomized trials (RCTs) in low-weight (<2.5 kg) infants have shown that Bacille Calmette-Guérin (BCG) vaccine nonspecifically reduces all-cause mortality in the neonatal period. Using data from 3 RCTs of early BCG (n = 6583) we examined potential sex differences in the timing of the mortality reduction in the neonatal period, presenting metaestimates of the main outcome mortality rate ratios (MRR) for BCG-vaccinated and controls. Among controls, boys had a particularly high mortality during the first week after randomization: male-female MRR 2.71 (95% CI, 1.70-4.50). During the first week, BCG had a marked beneficial effect for boys, reducing mortality 3-fold (MRR [BCG/no BCG] = 0.36 [0.20-0.67]). In weeks 2-4 the effect waned for boys (MRR = 0.91 [0.51-1.69]). In girls, the pattern was opposite with a limited effect in the first week (MRR = 0.85 [0.46-1.54]), but a significant reduction in weeks 2-4 (MRR = 0.56 [0.31-1.00]). This was consistent in all 3 trials. Verbal autopsies linked early benefit to fewer sepsis-related deaths among BCG-vaccinated boys. The marked reduction in mortality in the days after BCG vaccination in boys emphasizes the importance of providing BCG soon after birth. ClinicalTrials.gov (NCT00146302) and ClinicalTrials.gov (NCT00625482).

Epidemiology and impact on all-cause mortality of sepsis in Norwegian hospitals: A national retrospective study.

BackgroundAlthough sepsis is the leading cause of death from infection, there are few population-level epidemiological sepsis reports. The impact of sepsis-related deaths on all-cause hospital mortality is insufficiently described, in particular in Europe where data are non-existent. The objective of this study was to provide nationwide epidemiological results on sepsis hospitalizations in Norway and to estimate sepsis’ contribution to overall hospital mortality in a European setting.MethodsWe performed a retrospective study using data from the Norwegian Patient Registry and Statistics Norway. The occurrence, patient characteristics and outcomes of sepsis hospitalizations during the years 2011 and 2012 were estimated and compared with Norwegian population data. Sepsis was defined as organ dysfunction caused by a dysregulated host response to infection and identified with International Classification of Diseases 10th revision codes.ResultsWe identified 18 460 sepsis admissions occurring in 13 582 individuals. The annual population incidence of hospitalized sepsis was 140 patients per 100 000 inhabitants; ranging from 10 to 2270 per 100 000 in different age groups and with statistically significant male predominance in all adult cohorts. Hospital mortality for sepsis admissions was 19.4% and overall, 26.4% of the included patients died while hospitalized for sepsis. Sepsis related deaths constituted 12.9% of all hospital fatalities, while hospitalizations with sepsis accounted for 1.0% of the total number of admissions and 3.5% of the total admission days during 2011 and 2012.ConclusionsThis study confirms that hospitalized sepsis is frequent in Norway and a major contributor to hospital fatalities in a European setting. The incidence is higher among men than women. Sepsis is in particular a disease of the elderly, and its impact on health-care will assumingly continue to increase in parallel with an aging population. Improvements in treatment and survival of sepsis could influence population mortality, and sepsis should receive greater attention in official death statistics in the future.

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching*

The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. Use of aspirin was associated with a 7% (95% CI, 2-12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I = 61.6%). These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns)

Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI -4·6 to 4·8) in the intention-to-treat analysis (5 [0·6%] of 866 neonates in the procalcitonin group vs 4 [0·5%] of 844 neonates in the standard group) and 0·1% (-5·2 to 5·3) in the per-protocol analysis (5 [0·7%] of 745 neonates in the procalcitonin group vs 4 [0·6%] of 663 neonates in the standard group). Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death. The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.

Cost and mortality impact of an algorithm-driven sepsis prediction system

Aims: To compute the financial and mortality impact of InSight, an algorithm-driven biomarker, which forecasts the onset of sepsis with minimal use of electronic health record data.Methods: This study compares InSight with existing sepsis screening tools and computes the differential life and cost savings associated with its use in the inpatient setting. To do so, mortality reduction is obtained from an increase in the number of sepsis cases correctly identified by InSight. Early sepsis detection by InSight is also associated with a reduction in length-of-stay, from which cost savings are directly computed.Results: InSight identifies more true positive cases of severe sepsis, with fewer false alarms, than comparable methods. For an individual ICU with 50 beds, for example, it is determined that InSight annually saves 75 additional lives and reduces sepsis-related costs by $560,000.Limitations: InSight performance results are derived from analysis of a single-center cohort. Mortality reduction results rely on a simplified use case, which fixes prediction times at 0, 1, and 2 h before sepsis onset, likely leading to under-estimates of lives saved. The corresponding cost reduction numbers are based on national averages for daily patient length-of-stay cost.Conclusions: InSight has the potential to reduce sepsis-related deaths and to lead to substantial cost savings for healthcare facilities.

AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol

IntroductionSepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis...

Coagulopathy in sepsis - a new look at an old problem.

Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis. According to a recently described new theory, immunothrombosis is a immune response in which the local activation of coagulation facilitates the recognition and destruction of pathogens. Small amounts of clot formation are beneficial for the host because of bacteria trapping and prevention of the systemic spread of infection. Sepsis is a dynamic syndrome and in all patients with sepsis coagulation changes may progress from a normal profile to hypercoagulability and hypofibrinolysis, hyperfibrinolysis, and ultimately hypocoagulability.

ISQUA16-2735HOSPITAL VARIATIONS IN POSTOPERATIVE SEPSIS AND RELATED OUTCOMES AFTER CORONARY ARTERY BYPASS GRAFTING SURGERY

To assess hospital variations in the incidence rates of sepsis and sepsis related deaths, sepsis case fatality, overall in-hospital mortality and 30-day post-discharge mortality, as well as readmission within 28 days after discharge among elective surgical patients who underwent coronary artery bypass grafting (CABG) in New South Wales (NSW), Australia. We selected elective surgical patients who underwent CABG surgery performed in 9 public acute hospitals (all principal referral hospitals) and in 12 private hospitals (7 major, 2 district and 3 community) in NSW from 2007 to 2013 using the state-wide Admitted Patient Data Collection records linked with the NSW Registry of Births, Deaths, and Marriages. Following the inclusion criteria …

Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study.

Sepsis is one of the most common causes of neonatal deaths globally. Most sepsis-related deaths occur in low-income and middle-income countries, where the epidemiology of neonatal sepsis remains poorly understood. Most of these countries lack proper surveillance networks, hampering accurate assessment of the burden of sepsis, implementation of preventive measures, and investment in research. We report results of neonates born in hospital from a multicentre collaboration on neonatal sepsis. In this cohort study, dedicated research teams prospectively followed up neonates born in one of three tertiary care centres in Delhi, India (Vardhaman Mahavir Medical College, Maulana Azad Medical College, and All India Institute of Medical Sciences [coordinating centre]) and subsequently admitted to the intensive care unit. Neonates were followed up daily until discharge or death. On clinical suspicion, neonates underwent sepsis work-up including blood cultures. The isolated organisms were identified and tested for antimicrobial susceptibility. We defined Gram-negative isolates resistant to any three of five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) as multidrug resistant. 13 530 neonates of 88 636 livebirths were enrolled between July 18, 2011, and Feb 28, 2014. The incidence of total sepsis was 14·3% (95% CI 13·8-14·9) and of culture-positive sepsis was 6·2% (5·8-6·6). Nearly two-thirds of total episodes occurred at or before 72 h of life (defined as early onset; 1351 [83%] of 1980). Two-thirds (645 [64%]) of 1005 isolates were Gram-negative including, Acinetobacter spp (22%), Klebsiella spp (17%), and Escherichia coli (14%). The pathogen mix in early-onset sepsis did not differ from that of late-onset sepsis (ie, after 72 h). High rates of multidrug resistance were observed in Acinetobacter spp (181/222, 82%), Klebsiella spp (91/169, 54%), and Escherichia coli (52/137, 38%) isolates. Meticillin resistance prevailed in 61% (85/140) of coagulase-negative staphylococci and 38% (43/114) of Staphylococcus aureus isolates. Nearly a quarter of the deaths were attributable to sepsis. The population-attributable risks of mortality were 8·6% in culture-negative sepsis, 15·7% in culture-positive sepsis by multidrug-resistant organisms, and 12·0% in culture-positive sepsis by non-multidrug-resistant organisms. The high incidence of sepsis and alarming degree of antimicrobial resistance among pathogens in neonates born in tertiary hospitals underscore the need to understand the pathogenesis of early-onset sepsis and to devise measures to prevent it in low-income and middle-income countries. Indian Council of Medical Research.

Growing burden of sepsis-related mortality in northeastern Italy: a multiple causes of death analysis.

BackgroundFew population-based data are available on mortality due to sepsis. The aim of the study was to estimate sepsis-related mortality rates and to assess the associated comorbidities.MethodsFrom multiple causes of death data (MCOD) of the Veneto Region (northeastern Italy), all deaths with sepsis mentioned anywhere in the death certificate were retrieved for the period 2008–2013. Among these deaths the prevalence of common chronic comorbidities was investigated, as well as the distribution of the underlying cause of death (UCOD), the single disease selected from all condition mentioned in the certificate and usually tabulated in mortality statistics. Age-standardized mortality rates were computed for sepsis selected as the UCOD, and for sepsis mentioned anywhere in the certificate.ResultsOverall 16,906 sepsis-related deaths were tracked. Sepsis was mentioned in 6.3 % of all regional deaths, increasing from 4.9 in 2008 to 7.7 % in 2013. Sepsis was the UCOD in 0.6 % of total deaths in 2008, and in 1.6 % in 2013. Age-standardized mortality rates increased by 45 % for all sepsis-related deaths, and by 140 % for sepsis as the UCOD. Sepsis was often reported in the presence of chronic comorbidities, especially neoplasms, diabetes, circulatory diseases, and dementia. Respiratory tract and intra-abdominal infections were the most frequently associated sites of infection.ConclusionsMCOD analyses provide an estimate of the burden of sepsis-related mortality. MCOD data suggest an increasing importance attributed to sepsis by certifying physicians, but also a real increase in mortality rates, thus confirming trends reported in some other countries by analyses of hospital discharge records.