Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)

Abstract

BackgroundSepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability.MethodsData were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis.ResultsPatients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3–6.1, P < 0.01; disability OR 3.4, 95% CI 1.8–6.4, P < 0.001).ConclusionsDespite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2052-7) contains supplementary material, which is available to authorized users.

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

“…Despite important reductions in the number of cases as a result of vaccination programs, Neisseria meningitidis (meningococcal) disease is still a major cause of invasive bacterial infections globally. 1,2 Complex interplays among host, pathogen, and environment determine the severity of disease. [3][4][5][6] The severity of infection ranges from harmless nasopharyngeal colonization to bacteremia, meningitis, sepsis, and lethal disease.…”

“…The protein C pathway. TM binds circulating thrombin (1) and forms a TM-thrombin complex, which activates PC bound to EPCR into aPC(2). APC then dissociates from the EPCR, binds to PS, and forms a complex that inactivates factor Va and factor VIIIa (3).…”

Modern Diagnostics of Sepsis and Septic Shock in Children

“…It should also be noted that, according to research, most cases of sepsis occur before the age of 3 years, which can probably be associated with the anatomical and physiological characteristics of young children (11,19,20). Children with chronic comorbidities had a higher mortality rate (21,22).…”

“…Among hospital infections, gram-negative bacteria -Pseudomonas aeruginosa, Klebsiella species, E. coli, Acinetobacter species, and Salmonella spp -most often lead to sepsis. Catheter-associated sepsis is caused by coagulasenegative staphylococci (6,19,20,23).…”

Etiology, Antibiotic Susceptibility and Prognostic Factors of Pediatric Community-Acquired Sepsis in Addis Ababa, Ethiopia

“…4 Case-fatality rates due to CAS range from 6% to 13% and factors such as age, severity of illness at onset of sepsis, presence of comorbidities, bacteremia and etiology have been associated with mortality. [4][5][6][7] PCV10 was introduced in Ethiopia in October 2011 as a three dose primary series (3p+0) without any booster dose 8 . A study by Muhe and colleagues on CAS in children younger than three months of age in Addis Ababa Ethiopia performed two decades before the introduction of PCV10 in the country has identi ed S. pneumoniae as the predominant cause of sepsis.…”