Sepsis 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.
Data 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.
Patients 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).
Despite 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.
We conducted a retrospective, observational study of 42 children with intracranial empyema admitted to a pediatric neurosurgical center over a 9-year period. Intracranial empyema is rare, but causes ...significant morbidity and mortality. Twenty-eight cases had neurosurgical source control, more commonly for subdural collections.
Streptococcus anginosus
group bacteria are important pathogens in subdural empyema, whose isolation predicts more complicated postoperative courses.
Summary Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is ...linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.
Abstract Evidence suggests that Toll-like receptor 4 (TLR4) contributes to immune recognition of respiratory syncytial virus (RSV). The TLR4 gene harbours a polymorphism–Asp299Gly–previously ...associated with reduced TLR4 signalling. To understand of how host genetic variation influences the outcome of RSV infection in children, we examined the association between the TLR4 299Gly allele and severe RSV disease. By genotyping 236 children with RSV infection and 219 healthy controls we found no association between the risk of severe RSV infection and Asp299Gly polymorphisms ( P > 0.05), and we demonstrate that the TLR4 Asp299Gly genotype does not influence susceptibility to either RSV serotype A or B ( P > 0.05). Finally, examining the functional impact of the TLR4 Asp299Gly polymorphism ( n = 58), we demonstrate that proinflammatory cytokine production following TLR4 activation was indistinguishable between homozygous (Asp/Asp) and heterozygous (Asp/Gly) subjects. We conclude that the Asp299Gly TLR4 polymorphism does not alter receptor function and does not influence the risk of severe RSV infection.
Cystic echinococcosis is a zoonosis caused by the larvae of Echinococcus granulosus. Pulmonary disease may be asymptomatic until the cyst ruptures or becomes secondarily infected. We report a case of ...pulmonary cystic echinococcosis presenting in the United Kingdom, with discussion on management: optimum antihelminthic agent, length of treatment and type of operative intervention. Treatment should be individualized to the clinical scenario.
Following surgery, it is difficult to distinguish a postoperative inflammatory reaction from infection. This study examined the predictive value of the biomarkers; procalcitonin, C-reactive protein, ...lactate, neutrophils, lymphocytes, platelets, and the biphasic activated partial thromboplastin time waveform in diagnosing bacterial infection following cardiac surgery.
Prospective, observational study.
A regional, PICU in the United Kingdom.
Three-hundred sixty-eight children under the age of 16 admitted to the PICU for elective cardiac surgery were enrolled in the study.
All biomarker measurements were determined daily until postoperative day 7. Children were assessed for postoperative infection until day 28 and divided into four groups: bacterial infection, culture-negative sepsis, viral infection, and no infection. We used the Kruskal-Wallis test, chi-square test, analysis of variance, and area under the curve in our analysis.
In total, 71 of 368 children (19%) developed bacterial infection postoperatively, the majority being surgical site infections. In those with bacterial infection, procalcitonin was elevated on postoperative days 1-3 and the last measurement prior to event compared with those without bacterial infection. The most significant difference was the last measurement prior to event; 0.72 ng/mL in the bacterial infection group versus 0.13 ng/mL in the no infection group (for all groups; p < 0.001). Longitudinal profiles of all biomarkers were indistinct in the bacterial infection and nonbacterial infection groups except in those with culture-negative infections who had distinct procalcitonin kinetics on postoperative days 1-4. Children with culture-negative sepsis required longer ventilatory support and PICU stay and were more likely to develop complications than the other groups.
None of the biomarkers studied within 3 days of infection distinguished between infection and postoperative inflammatory reaction. However, procalcitonin kinetics peaked on postoperative day 2 and fell more sharply than C-reactive protein kinetics, which peaked at postoperative day 3. The monitoring of procalcitonin kinetics following cardiac surgery may help guide rational antimicrobial use.
BackgroundThe National Health Service England, Commissioning for Quality and Innovation for Antimicrobial Resistance (CQUIN AMR) aims to reduce the total antibiotic consumption and the use of certain ...broad-spectrum antibiotics in secondary care. However, robust baseline antibiotic use data are lacking for hospitalised children. In this study, we aim to describe, compare and explain the prescription patterns of antibiotics within and between paediatric units in the UK and to provide a baseline for antibiotic prescribing for future improvement using CQUIN AMR guidance.MethodsWe conducted a cross-sectional study using a point prevalence survey (PPS) in 61 paediatric units across the UK. The standardised study protocol from the Antibiotic Resistance and Prescribing in European Children (ARPEC) project was used. All inpatients under 18 years of age present in the participating hospital on the day of the study were included except neonates.ResultsA total of 1247 (40.9%) of 3047 children hospitalised on the day of the PPS were on antibiotics. The proportion of children receiving antibiotics showed a wide variation between both district general and tertiary hospitals, with 36.4% ( 95% CI 33.4% to 39.4%) and 43.0% (95% CI 40.9% to 45.1%) of children prescribed antibiotics, respectively. About a quarter of children on antibiotic therapy received either a medical or surgical prophylaxis with parenteral administration being the main prescribed route for antibiotics (>60% of the prescriptions for both types of hospitals). General paediatrics units were surprisingly high prescribers of critical broad-spectrum antibiotics, that is, carbapenems and piperacillin-tazobactam.ConclusionsWe provide a robust baseline for antibiotic prescribing in hospitalised children in relation to current national stewardship efforts in the UK. Repeated PPS with further linkage to resistance data needs to be part of the antibiotic stewardship strategy to tackle the issue of suboptimal antibiotic use in hospitalised children.
IntroductionProcalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in ...the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children.Methods and analysisBiomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic.Ethics and disseminationThe trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings.Trial registration numberISRCTN11369832.
We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, ...H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection.
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