Impact of the Step-by-Step on febrile infants

ObjectiveTo evaluate the impact of introducing the Step-by-Step approach on care quality in young febrile infants.DesignObservational study including infants ≤90 days old with fever without source seen in a paediatric emergency department 5 years before (n=1222) and after (n=1151) its introduction. Quality of care was evaluated in terms of adherence to recommendations, resource use and safety.ResultsAdherence: percentages of infants undergoing both urine and blood tests and infants <15 days old receiving full sepsis evaluation increased (84.7% vs 91.0% and 23.9% vs 63.3%, respectively; p<0.01). Resource use: lumbar puncture and admission rates decreased (24.1% vs 18.7% and 43.6% vs 38.3%, respectively; p<0.01), while the rate of antibiotic therapy increased (30.2% vs 43.2%; p<0.01). Safety: the invasive bacterial infection rate among infants managed as outpatients was unchanged (0.7% vs 0.3%; p=0.24).ConclusionThe introduction of the Step-by-Step increased the quality of care provided to young febrile infants.

A retrospective review of serious infections in febrile infants 0–90 days old

Background: Fever without source in infants is a common clinical problem that accounts for many ambulatory care visits and hospitalisations. Currently, there is no reliable method of identifying those at risk of serious infection (SI). Objective: The goal of this study was to determine the incidence and identify the predictors of SI in febrile infants who presented to the emergency department (ED). Methods: This was a single-centre retrospective cohort study of children presenting to a Singapore tertiary hospital paediatric unit between 1 July 2018 and 31 December 2018. Children were included if they were aged 0–90 days and presented to the ED with a fever. SI was defined as urinary tract infection (UTI), sepsis, bacteraemia, meningitis (viral and bacterial), enterocolitis, osteomyelitis, abscess or pneumonia. Results: Of the 659 infants, 161 (24.4%) were diagnosed with SI. Meningitis (49.7%) was the most common SI, followed by UTI (45.3%), enterocolitis (5.6%), sepsis (3.1%) and bacteraemia (2.5%). Factors significantly associated with SI were aged 29–60 days, male sex, Severity Index Score (SIS) <10, absolute neutrophil counts >10×109/L, C-reactive protein (CRP) >20 mg/L and procalcitonin >0.5 ng/mL. Multivariate analysis entering all these items retained only male sex, SIS <10 and CRP >20. Conclusion: Among hospitalised infants aged 0–90 days, the incidence of SI was 24.4%, and invasive bacterial infection was 0.6%. Meningitis was the most common SI followed by UTI. SIS and CRP can be used to predict SI in infants <90 days old.

Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity

Goblet cells are essential for maintaining intestinal health and for the defense against invasive bacterial infection. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. Here we found that epithelial Gpr35 plays a critical role in goblet cell function. Genetic deletion of Gpr35 in epithelial cells but not in from macrophages results in goblet cell depletion and dysbiosis, rendering these mice more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows how the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota.

Invasive Bacterial Infections in Subjects with Genetic and Acquired Susceptibility and Impacts on Recommendations for Vaccination: A Narrative Review

The WHO recently endorsed an ambitious plan, “Defeating Meningitis by 2030”, that aims to control/eradicate invasive bacterial infection epidemics by 2030. Vaccination is one of the pillars of this road map, with the goal to reduce the number of cases and deaths due to Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus agalactiae. The risk of developing invasive bacterial infections (IBI) due to these bacterial species includes genetic and acquired factors that favor repeated and/or severe invasive infections. We searched the PubMed database to identify host risk factors that increase the susceptibility to these bacterial species. Here, we describe a number of inherited and acquired risk factors associated with increased susceptibility to invasive bacterial infections. The burden of these factors is expected to increase due to the anticipated decrease in cases in the general population upon the implementation of vaccination strategies. Therefore, detection and exploration of these patients are important as vaccination may differ among subjects with these risk factors and specific strategies for vaccination are required. The aim of this narrative review is to provide information about these factors as well as their impact on vaccination against the four bacterial species. Awareness of risk factors for IBI may facilitate early recognition and treatment of the disease. Preventive measures including vaccination, when available, in individuals with increased risk for IBI may prevent and reduce the number of cases.

Eculizumab-Associated Moraxella lacunata Bacteremia and Systemic Inflammatory Response Syndrome in a Toddler with Atypical Hemolytic Uremic Syndrome

Moraxella lacunata, a low-virulence Gram-negative coccobacillus, is classically associated with conjunctivitis and upper respiratory tract infections; systemic infections such as sepsis have rarely been reported, especially in children. We describe a 28-month-old girl with atypical hemolytic uremic syndrome and stage II chronic kidney disease on long-term eculizumab therapy who presented with systemic inflammatory response syndrome and was found to have Moraxella lacunata bloodstream infection. Eculizumab, a humanized monoclonal anti-C5 antibody, has been associated with susceptibility to infections with encapsulated bacteria, especially Neisseria meningitidis. This is the first report of an invasive bacterial infection with Moraxella lacunata in a pediatric eculizumab recipient.

Diagnostic Value of Mid-regional Pro-adrenomedullin (MR-proADM) as a Biomarker of Invasive Bacterial Infection in Children: A Systematic Review.

BackgroundIn children differentiating between the early stages of an invasive bacterial infection (IBI) and a benign self-limiting viral infection remains clinically challenging. This often leads to an over-use of antimicrobial drugs with resultant antimicrobial resistance due to the concern of not detecting a deteriorating child. Hence research into novel biomarkers for the early identification of IBI in children is of increasing interest. A more timely diagnosis through more accurate biomarkers may lead to improved clinical outcomes for children and reduced antimicrobial resistance. Mid-regional pro-adrenomedullin (MR-proADM) is a biomarker that is found at elevated levels in patients with IBI compared with those with viral infections. The aim of this systematic review was to determine the diagnostic accuracy of MR-proADM at identifying children with IBI. MethodsWe searched MEDLINE, Embase, Web of Science and Scopus from 1980 to the present day for all human clinical trials involving children that report the test accuracy of MR-proADM. Eligibility was assessed by screening titles and abstracts of articles found during the search process. This was then followed by full-text assessment and data extraction. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the methodological quality of identified studies. The following test characteristics were extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. ResultsA total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed. 4 studies (totaling 1404 patients) were able to be included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible.ConclusionThere is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI. Trial registrationPROSPERO CRD42018096295

Height of fever and invasive bacterial infection

ObjectiveWe aimed to evaluate the association of height of fever with invasive bacterial infection (IBI) among febrile infants <=60 days of age.MethodsIn a secondary analysis of a multicentre case–control study of non-ill-appearing febrile infants <=60 days of age, we compared the maximum temperature (at home or in the emergency department) for infants with and without IBI. We then computed interval likelihood ratios (iLRs) for the diagnosis of IBI at each half-degree Celsius interval.ResultsThe median temperature was higher for infants with IBI (38.8°C; IQR 38.4–39.2) compared with those without IBI (38.4°C; IQR 38.2–38.9) (p<0.001). Temperatures 39°C–39.4°C and 39.5°C–39.9°C were associated with a higher likelihood of IBI (iLR 2.49 and 3.40, respectively), although 30.4% of febrile infants with IBI had maximum temperatures <38.5°C.ConclusionsAlthough IBI is more likely with higher temperatures, height of fever alone should not be used for risk stratification of febrile infants.

Surveillance for Invasive Salmonella Disease in Bamako, Mali, From 2002 to 2018

Background Salmonella enterica bloodstream infections are an important cause of childhood morbidity and mortality, including in Mali. We report 17 years of surveillance for nontyphoidal and typhoidal S. enterica infections among inpatients and outpatients at l’Hôpital Gabriel Touré, the main source of pediatric tertiary care in Bamako, Mali. Methods Between June 2002 and December 2018, a blood culture was collected from 54 748 children aged ≤15 years with fever and/or suspected invasive bacterial infection who provided consent (38 152 inpatients, 16 596 outpatients). Bacterial pathogens were identified using standard microbiological techniques and serovars of S. enterica were determined by PCR and/or agglutination with antisera. Results Nontyphoidal Salmonella (NTS) was identified in 671 enrolled inpatients (1.8% of all enrolled inpatients, 13.8% of enrolled inpatients with a positive culture). S. Enteritidis, the most common NTS serovar, accounted for 38.5% of all NTS isolates (n = 258), followed by S. Typhimurium (31.7%, n = 213). The median (SD) age of children with a culture positive for NTS was 1.8 (3) years. Overall case fatality was 20.9%. An additional 138 inpatients (0.4%) had a positive culture for typhoidal Salmonella. NTS was identified in 11 outpatients (0.07%), while typhoidal Salmonella was found in 49 outpatients (0.3%). The annual incidence of invasive NTS disease decreased over the study period, but case fatality remained high. Conclusions Although incidence decreased, NTS remained a major cause of invasive bacterial infection and mortality among hospitalized children in Bamako, while typhoidal Salmonella was uncommon. Because 87% of NTS belonged to only 4 serovars, a multivalent vaccine may be an effective strategy to reduce the burden and mortality of invasive NTS.