Sepsis In Young Infants Research Articles

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

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

World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study.

Bacterial sepsis is generally a major concern in ill infants. To help triaging decisions by front-line health workers in these situations, the World Health Organization (WHO) has developed danger signs (DS). The objective of this study was to evaluate the extent to which nine DS predict bacterial sepsis in young infants presenting with suspected sepsis in a low-income country setting. The study pragmatically evaluated nine DS in infants younger than 3 months with suspected sepsis in a regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. Main outcomes were positive blood or cerebrospinal fluid (CSF) cultures for neonatal pathogens, and mortality. Among 401 infants (gestational age [mean ± SD]: 37.1±3.3 weeks, birth weight 2865±785 grams), 41 had positive blood or CSF cultures for a neonatal pathogen. In-hospital mortality occurred in 9.7% of infants overall (N = 39/401), of which 61.5% (24/39) occurred within 48 hours of admission. Mortality was higher in infants with bacterial sepsis compared to other infants (22.0% [9/41] versus 8.3% [30/360]; p = 0.005). All DS were associated with mortality except for temperature instability and tachypnea, whereas none of the DS were significantly associated with bacterial sepsis, except for "unable to feed" (OR 2.25; 95%CI: 1.17-4.44; p = 0.017). The number of DS predicted mortality (OR: 1.75; 95%CI: 1.43-2.17; p<0.001; AUC: 0.756), but was marginally associated with positive cultures with a neonatal pathogen (OR 1.22; 95%CI: 1.00-1.49; p = 0.046; AUC: 0.743). The association between number of DS and mortality remained significant after adjusting for admission weight, the only statistically significant co-variable (OR 1.75 [95% CI: 1.39-2.23]; p<0.001). Considering all positive cultures including potential bacterial contaminants resulted a non-significant association between number of DS and sepsis (OR 1.09 [95% CI: 0.93-1.28]; p = 0.273). In conclusion, this study shows that DS were strongly associated with death, but were marginally associated with culture-positive pathogen sepsis in a regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality in infants in LMIC settings may be inaccurately estimated based on clinical signs alone.

Decreasing Variation to Enhance Accurate Identification of Hypothermic Infants in Pediatric Primary Care.

Hypothermia can be the first and only sign of sepsis in young infants, yet there is a paucity of standard recommendations for pediatric primary-care office management of those infants identified. The SMART aim of this study was to standardize the identification and care of infants age 0 to 49 days at risk of hypothermia in pediatric primary care by decreasing the percent of infants with temperatures ≤36.5°C from 24% to 10% within 2 years. Over the course of this project, variation in documented temperatures ≤36.5°C decreased from 24% to 7% of encounters. Temperatures ≤36.5°C were documented for 951 infants or 13.4% (1078 of 8020 encounters). Of the 951 infants with temperatures ≤36.5°C, 96.1% were rewarmed in the office. Thirty-one patients ultimately required hospitalization. Application of quality improvement in a primary-care office decreased low temperatures by standardizing care, empowering staff, and triaging at-risk infants to the most appropriate level of care.

Cronobacter sakazakii Infections in Two Infants Linked to Powdered Infant Formula and Breast Pump Equipment - United States, 2021 and 2022.

Cronobacter sakazakii, a species of gram-negative bacteria belonging to the Enterobacteriaceae family, is known to cause severe and often fatal meningitis and sepsis in young infants. C. sakazakii is ubiquitous in the environment, and most reported infant cases have been attributed to contaminated powdered infant formula (powdered formula) or breast milk that was expressed using contaminated breast pump equipment (1-3). Previous investigations of cases and outbreaks have identified C. sakazakii in opened powdered formula, breast pump parts, environmental surfaces in the home, and, rarely, in unopened powdered formula and formula manufacturing facilities (2,4-6). This report describes two infants with C. sakazakii meningitis reported to CDC in September 2021 and February 2022. CDC used whole genome sequencing (WGS) analysis to link one case to contaminated opened powdered formula from the patient's home and the other to contaminated breast pump equipment. These cases highlight the importance of expanding awareness about C. sakazakii infections in infants, safe preparation and storage of powdered formula, proper cleaning and sanitizing of breast pump equipment, and using WGS as a tool for C. sakazakii investigations.

Zinc Supplementation and the Prevention and Treatment of Sepsis in Young Infants: A Systematic Review and Meta-Analysis

Background: Prematurity and low birth weight are major risk factors for neonatal sepsis. Zinc supplements have been previously shown to be beneficial in pregnancy and small for gestational age birth outcomes. There is sparse information, however, on the potential benefits of zinc supplementation to prevent or treat serious infections in this age group. Objective: The aim of this study was to assess the efficacy of preventive and therapeutic zinc supplementation in young infant (<4 months) sepsis. Methods: MEDLINE, Cochrane CENTRAL, and other databases were searched from inception until 18 June 2021. Studies assessing preventive and therapeutic zinc supplementation in young infants in relation to incidence and outcomes of suspected sepsis were included. Meta-analyses of pooled effects were calculated for sepsis-related outcomes. Results: Nine randomized controlled trials involving 2,553 infants were included. Six studies reported therapeutic efficacy, whereas 3 evaluated preventive benefits of zinc supplementation. Preventive studies suggest a protective effect of zinc supplementation on neonatal mortality rate (NMR) (risk ratio (RR) 0.28; 95% CI 0.12–0.67, LOW certainty), but with no effect on the incidence of sepsis, both in preterm neonates. Among young infants, therapeutic zinc was associated with significant reductions in treatment failure (RR 0.61; 95% CI 0.44–0.85; MODERATE certainty) and further subgroup analysis showing significant reduction in infant mortality rate with 3 mg/kg/twice a day dosage only (RR 0.49; 95% CI 0.27–0.87, LOW certainty). Therapeutic zinc supplementation in neonates did not show any effect on hospital stay or NMR. Conclusion: Zinc supplementation could potentially reduce mortality and treatment failure in young infants but has no noteworthy influence on hospital stay and in the prevention of sepsis. Further studies with larger sample sizes are needed to confirm the direction and magnitude of effects if any.

1110. In Vivo Pharmacodynamics of Vancomycin Against Staphylococci in Young Infants

BackgroundCoagulase-negative staphylococci are the predominant pathogen causing late onset sepsis in young infants, however, the pharmacodynamic target for vancomycin therapy is unknown. This study aimed to determine the pharmacodynamic target of vancomycin in young infants with staphylococcal infections.MethodsRetrospective data were collected for infants aged 0-90 days with methicillin-resistant Staphylococcus aureus (MRSA or coagulase-negative staphylococci (CoNS) bacteraemia over a 4-year period at the Royal Children’s Hospital Melbourne, Australia. Vancomycin broth microdilution minimum inhibitory concentrations (MIC) were determined. A published pharmacokinetic model was externally validated using the study dataset and a time-to-event pharmacodynamic model developed using non-linear mixed effects modelling, with the event being the first negative blood culture. Simulations were performed to determine the 24-hour trough vancomycin concentration correlating with a 90% probability target attainment (PTA) of the area under the curve in the first 24-hours (AUC0-24) exceeding the identified target.ResultsThirty infants, 28 with CoNS and two with MRSA bacteraemia, who had 165 vancomycin concentrations determined were included. The vancomycin broth microdilution MIC was determined for 24 CoNS and one MRSA isolate, both with a median MIC of 1 mg/L (CoNS range 0.5 to 4). An AUC0-24 ≥3 00 mg/L·h was associated with a 7.8-fold increase in the chance of bacteriological cure for all staphylococci at any time point compared to an AUC0-24 < 300 mg/L·h (hazard ratio 95% CI: 3.21-18.8). The 24-hour trough concentrations associated with a 90% PTA of achieving this target were > 13-16 mg/L and > 8-12 mg/L for 6 and 12-hourly dosing, respectively. ConclusionOur study found that an AUC0-24 ≥ 300 mg/L·h was associated with a 7.8-fold increase in bacteriological cure in young infants with staphylococcal bloodstream infections. Disclosures All Authors: No reported disclosures

Antimicrobial susceptibilities and comparative whole genome analysis of two isolates of the probiotic bacterium Lactiplantibacillus plantarum, strain ATCC 202195

A synbiotic containing Lactiplantibacillus plantarum [American Type Culture Collection (ATCC) strain identifier 202195] and fructooligosaccharide was reported to reduce the risk of sepsis in young infants in rural India. Here, the whole genome of two isolates of L. plantarum ATCC 202195, which were deposited to the ATCC approximately 20 years apart, were sequenced and analyzed to verify their taxonomic and strain-level identities, identify potential antimicrobial resistant genes and virulence factors, and identify genetic characteristics that may explain the observed clinical effects of L. plantarum ATCC 202195. Minimum inhibitory concentrations for selected antimicrobial agents were determined using broth dilution and gradient strip diffusion techniques. The two L. plantarum ATCC 202195 isolates were genetically identical with only three high-quality single nucleotides polymorphisms identified, and with an average nucleotide identity of 99.99%. In contrast to previously published reports, this study determined that each isolate contained two putative plasmids. No concerning acquired or transferable antimicrobial resistance genes or virulence factors were identified. Both isolates were sensitive to several clinically important antibiotics including penicillin, ampicillin and gentamicin, but resistant to vancomycin. Genes involved in stress response, cellular adhesion, carbohydrate metabolism and vitamin biosynthesis are consistent with features of probiotic organisms.

Early congenital syphilis, an old disease still occurring in the modern era: case report and literature review

Introduction. Congenital syphilis is a well-known infectious disease caused by the passing of Treponema pallidum from the infected mother to the fetus. In most cases, it leads to fetal death. Still, in the survivors, it can manifest clinically as early congenital syphilis in the first two years of life or late congenital syphilis afterward. Current epidemiological data suggest that the incidence is very low in developed coun­tries due to screening. Case report. We report the case of a 2-month-old male infant who presented with a sepsis-like picture, generalized edema, and hepatosplenomegaly. He had elevated inflammatory markers (C-reactive protein and procalcitonin), acute kidney injury, and fulminant liver failure. The radiographic exam revealed periostitis of the long bones. The brain magnetic resonance imaging (MRI) revealed encephalitis, ventriculomegaly and cerebral atrophy, suggesting neurosyphilis. The diagnosis of con­ge­ni­tal syphilis was confirmed by the positive Venereal Disease Research Laboratory (VDRL) test. We initiated the treatment with penicillin, then we associated ceftriaxone for neurological involvement. He also needed blood trans­fu­sions due to severe anemia and thrombocytopenia, diu­re­tics, and hydrocortisone treatment. Conclusions. There are cases when screening methods are omitted, therefore congenital syphilis should always be considered in the differential diagnosis of sepsis in young infants.

Hypothermia: A Sign of Sepsis in Young Infants in the Emergency Department?

Diagnosis of sepsis in young infants can be challenging due to the nonspecific signs, which can include hypothermia. Whether the presence of hypothermia in young infants should prompt evaluation for serious infection is unclear. The objectives were to measure the prevalence of serious infection among infants ≤60 days of age with hypothermia in the emergency department (ED) and determine other clinical features of hypothermic infants who have serious infection. This is a retrospective analysis of all infants ≤60 days seen in a children's hospital ED from April 2014 to February 2017. Primary outcome was presence of serious infection, defined as urinary tract infection, bacteremia, meningitis, pneumonia, or herpes virus infection. Hypothermia was defined as a rectal temperature of 36.0°C or less. Of 4797 infants ≤60 days of age seen in the ED, 116 had hypothermia. The prevalence of serious infection was 2.6% (3/116) in hypothermic infants compared with 15.2% (61/401) in febrile infants (P < 0.01). Hypothermic infants with serious infections were more likely to have a history of prematurity, apnea, poor feeding, lethargy, ill-appearance, and respiratory signs than hypothermic infants without serious infection. All 3 hypothermic infants with serious infection had other concerning features. The prevalence of serious infection in hypothermic young infants in the ED is low. Serious infection is unlikely in infants with isolated hypothermia.

Protocol for a randomised controlled trial of continuous infusions of vancomycin to improve the attainment of target vancomycin levels in young infants: The VANC trial

IntroductionVancomycin is frequently used in the treatment of late-onset sepsis in young infants and is routinely administered as intermittent infusions (IIV); however, existing IIV dosing guidelines achieve target vancomycin levels...

Cerebral imaging and neurodevelopmental outcome after entero- and human parechovirus sepsis in young infants

Enterovirus (EV) and human parechovirus (HPeV) are major causes of sepsis-like illness in infants under 90 days of age and have been identified as neurotropic. Studies about acute and long-term neurodevelopment in infants with sepsis-like illness without the need for intensive care are few. This study investigates cerebral imaging and neurodevelopmental outcome following EV and HPeV infection in these infants. We studied infants under 90 days of age who were admitted to a medium care unit with proven EV- or HPeV-induced sepsis-like illness. In addition to standard care, we did a cerebral ultrasound and cerebral magnetic resonance imaging (MRI), as well as neurodevelopmental follow-up at 6 weeks and 6 months and Bayley Scale of Infant and Toddler Development 3rd edition (BSID-III) investigation at 1 year of age. Twenty-six infants, 22 with EV and 4 with HPeV, were analysed. No abnormalities were detected at cerebral imaging. At 1 year of age, two infants had a moderate delay on both the motor and cognitive scale, one on the cognitive scale only and three others on the gross motor scale only.Conclusion: Although our study population, especially the number of HPeV positive infants is small, our study shows that these infants do not seem to develop severe neurodevelopmental delay and neurologic sequelae more often than the normal Dutch population. Follow-up to school age allows for more reliable assessments of developmental outcome and is recommended for further studies to better assess outcome.What is known:• Enterovirus and Human Parechovirus infections are a major cause of sepsis-like illness in young infants.• After intensive care treatment for EV or HPeV infection, white matter abnormalities and neurodevelopmental delay have been described.What is new:• In our ‘medium care’ population, no abnormalities at cerebral imaging after EV- or HPeV-induced sepsis-like illness have been found.• At 1 year of age, infants who had EV- or HPeV-induced sepsis-like illness do not seem to develop severe neurodevelopmental delay and neurologic sequelae more often than the normal population.

Study of causative agent &amp; their susceptibility pattern in sepsis in young infants below 3 months of age

Introduction: Pathogens causing blood stream infections and their antibiotic susceptibility patterns constantly change over time & it is essential to monitor the epidemiology of infections to design appropriate antibiotic policy. Methodology: Blood culture reports of Children below 3 months of age admitted to our hospital over a period of 4 years were analysed to find the causative agents of sepsis & their antibiotic susceptibilities. All data were collected in validated preformatted proforma sheet & analysed using appropriate statistical methods. Results: Among 1401 blood cultures, culture positive growth was observed in 226 cases (16.1 %). In our study, Klebsiella pneumoniae was the commonest isolated in 23.4 % of blood cultures. Acinetobacter baumanii was the next commonest organism isolated in 13.7 % followed by MRSA growth in 11.9 %, MSSA in 4.8 %, E.coli in 8.8 %, Enterococcus faecalis in 7.5 %, B.cepacia in 6.6 %, P. aeruginosa in 5.3% & Enterobacter in 4.4 % of blood cultures. About 49% of K. pneumoniae were susceptible to Carbapenam & 60% of E.coli were susceptible to Amikacin & Tobramycin. All Enterobacter were sensitive to Imipenam, Meropenam, Ertapenam & Amikacin & 77% of A.baumanii were sensitive to Carbapenam. Yeasts were isolated in 8.4 %, the commonest being Candida tropicalis. Conclusion: It is essential to closely monitor the bacterial flora and their antibiotic sensitivity pattern to evolve rational antibiotic policy which is suitable for each unit. Guidelines on the reduction of emergence of drug resistance must be provided and instituted within the units.

Increased risk for group B Streptococcus sepsis in young infants exposed to HIV, Soweto, South Africa, 2004-2008(1).

Although group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants worldwide, epidemiologic data and knowledge about risk factors for the disease are lacking from low- to middle-income countries. To determine the epidemiology of invasive GBS disease among young infants in a setting with high maternal HIV infection, we conducted hospital-based surveillance during 2004-2008 in Soweto, South Africa. Overall GBS incidence was 2.72 cases/1,000 live births (1.50 and 1.22, respectively, among infants with early-onset disease [EOD] and late-onset [LOD] disease). Risk for EOD and LOD was higher for HIV-exposed than HIV-unexposed infants. GBS serotypes Ia and III accounted for 84.0% of cases, and 16.9% of infected infants died. We estimate that use of trivalent GBS vaccine (serotypes Ia, Ib, and III) could prevent 2,105 invasive GBS cases and 278 deaths annually among infants in South Africa; therefore, vaccination of all pregnant women in this country should be explored.

Sepsis in young infants with congenital heart disease

We sought to describe the incidence, pathogen distribution, and mortality associated with blood culture-proven sepsis in young infants with congenital heart disease (CHD) admitted to a neonatal intensive care unit (NICU). Cohort study of all blood cultures obtained from infants with CHD between 4 and 120 days of age cared for in 250 NICUs managed by the Pediatrix Medical Group in the United States between 1996 and 2007. Of 11,638 infants with CHD, 656 (6%) had 821 episodes of sepsis: a cumulative incidence of 71/1000 admissions. Gram-positive organisms were the most common cause (64%), and coagulase-negative Staphylococcus and Staphylococcus aureus were the most frequently isolated species. On multivariable regression, infants with sepsis were more likely to die compared to infants with sterile blood cultures (odds ratio [OR] = 1.53 [95% confidence interval: 1.09, 2.13]). Infants with Gram-negative bacteraemia and candidaemia were more likely to die than infants with sterile blood cultures (OR = 2.01 [1.20, 3.37], and OR = 3.18 [1.60, 6.34], respectively). Infants with CHD have a high incidence of culture-proven sepsis, especially with staphylococcal organisms. Gram-negative bacteraemia and candidaemia are strongly associated with increased mortality in this group of young infants.

Perianal Cellulites Associated with Group A Streptococci in Iranian Children

Methods: Sterile site isolates from infants less than 3 months of age admitted to CHBH were collected prospectively between January 2004 and December 2006. Clinical data were abstracted from the subjects’ medical records. Results: 1388 significant bacterial isolates from blood and cerebrospinal fluid were identified. Six pathogens accounted for 69.5% (965/1388) of the isolates. The most common isolate was Streptococcus agalactiae (n = 206; 14.8%) followed by Staphylococcus aureus (n = 185; 13.3%), Escherichia coli (n = 163; 11.7%), Viridans streptococcus (n = 148; 10.7%), Klebsiella pneumoniae (n = 146; 10.5%) and Acinetobacter baumanii (n = 119; 8.6%). 18% (37/206) of Streptococcus agalactiae isolates and 11% (18/163) of Escherichia coli isolates were from cerebrospinal fluid, compared to ≤10% in other pathogens. 83/172 (40.2%) of Streptococcus agalactiae (GBS) isolates were from infants ≤3 days of age. Incidence of early-onset (EO) GBS sepsis is 1.1/1000 live births. 89/172 (51.7%) of GBS isolates were from infants 4 days to 3 months of age, giving incidence of late-onset sepsis (LOS) of 1.2/1000 live births. Mean age of infants with LOS GBS sepsis is 12.5 days. S. aureus, E. coli, Viridans streptococcus and K. pneumoniae sepsis are predominantly LOS, with mean age of LOS cases being 31, 31, 24 and 35 days old respectively. Conclusions: Vertically transmitted bacteria are a significant cause of sepsis in young infants in South Africa. The increasing incidence of community-acquired Staphylococcus aureus sepsis in young infants is concerning and requires further investigation.

Sinusitis

Paranasal sinusitis is reported as a complication of prolonged nasal intubation and the source of sepsis in adult intensive care patients. In surgical neonates with congenital malformations, prolonged intubation with a nasotracheal (NT) or NG tube is often necessary, but sinusitis with complicating sepsis is seldom reported. Sinus x-rays may confirm the diagnosis; in infancy, prolonged nasal intubation delays the pneumatization of the sinuses and the mastoids, resulting in additional diagnostic problems. In a 1-yr period, we saw three patients with multiple septic episodes in which the source of sepsis was undetectable. Despite the absence of clinical symptoms and radiologic evidence of sinusitis or mastoiditis, surgical drainage revealed pus and led to the disappearance of septic episodes and ear, nose, and throat problems. There is an association between prolonged NT and NG intubation, and sinusitis or mastoiditis as an unrecognized source of sepsis in young infants. Absence of radiologic evidence of sinusitis or mastoiditis causes pitfalls in diagnosis and is related to delayed pneumatization of the sinuses and the mastoid in prolonged nasal intubation in young infants.

Role of the virology laboratory in diagnosis and management of patients with central nervous system disease.

A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection.

Viral and bacterial pathogens of suspected sepsis in young infants.

Clinical and laboratory data of 27 previously normal, healthy infants 2 months of age or less who were hospitalized for suspected sepsis during a 1-year period were reviewed. Results of bacterial cultures and viral studies revealed enteroviruses (seven echoviruses, one coxsackievirus) to be the predominant pathogens identified. Other viruses identified were one each of adenovirus, untypeable hemadsorbing virus and respiratory syncytial virus. Group B streptococcal and enterococcal bacteremia and salmonellosis were diagnosed in one case each. Gram-negative bacillary urinary tract infections occurred in two patients. No pathogens were identified in 11 patients. Although these data indicate an important role for enteroviruses in this syndrome during summer and fall, we believe that the occult bacteremia found in 7% of our patients justifies initial antibiotic therapy in very young infants with suspected sepsis.