Laurence Elisabeth Lacroix

Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source

Objective The identification of severe bacterial infection (SBI)in children with fever without source (FWS) remains a diagnostic problem. The authors previously developed in their Swiss population a risk index score, called the Lab-score, associating three independent predictors of SBI, namely C reactive protein (CRP), procalcitonin (PCT) and urinary dipstick. The objective of this study was to validate the Lab-score in a population of children with FWS different from the derivation model. Methods A prospective study, conducted in Padova, on 408 children aged 7 days to 36 months with FWS was recently published. PCT, CRP, white blood cell count (WBC) and urinary dipstick were determined in all children. The Lab-score was applied to this population and the diagnostic characteristics for the detection of SBI were calculated for the Lab-score and for any single variable used in the Italian study. Results For the identification of SBI, the sensitivity of a score ≥3 was 86% (95% CI 77% to 92%) and the specificity 83% (95% CI 79% to 87%). The area under the receiver operating characteristic curve for the Lab-score (0.91) was significantly superior to that of any single variable: 0.71 for WBC, 0.86 for CRP and 0.84 for PCT. The Lab-score performed better than other laboratory markers, even when applied to children of different age groups (<3 months, 3–12 months and >12 months). The results obtained in this validation set population were comparable with those of the derivation set population. Conclusions This study validated the Lab-score as a valuable tool to identify SBI in children with FWS.

Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants

BACKGROUND: A sequential approach to young febrile infants on the basis of clinical and laboratory parameters, including procalcitonin, was recently described as an accurate tool in identifying patients at risk for invasive bacterial infection (IBI). Our aim was to prospectively validate the Step-by-Step approach and compare it with the Rochester criteria and the Lab-score. METHODS: Prospective study including infants ≤90 days with fever without source presenting in 11 European pediatric emergency departments between September 2012 and August 2014. The accuracy of the Step-by-Step approach, the Rochester criteria, and the Lab-score in identifying patients at low risk of IBI (isolation of a bacterial pathogen in a blood or cerebrospinal fluid culture) was compared. RESULTS: Eighty-seven of 2185 infants (4.0%) were diagnosed with an IBI. The prevalence of IBI was significantly higher in infants classified as high risk or intermediate risk according to the Step by Step than in low risk patients. Sensitivity and negative predictive value for ruling out an IBI were 92.0% and 99.3% for the Step by Step, 81.6% and 98.3% for the Rochester criteria, and 59.8% and 98.1% for the Lab-score. Seven infants with an IBI were misclassified by the Step by Step, 16 by Rochester criteria, and 35 by the Lab-score. CONCLUSIONS: We validated the Step by Step as a valuable tool for the management of infants with fever without source in the emergency department and confirmed its superior accuracy in identifying patients at low risk of IBI, compared with the Rochester criteria and the Lab-score.

Impact of the lab-score on antibiotic prescription rate in children with fever without source: a randomized controlled trial

Background The Lab-score, based on the combined determination of procalcitonin, C-reactive protein and urinary dipstick results, has been shown accurate in detecting serious bacterial infections (SBI) in children with fever without source (FWS) on retrospective cohorts. We aimed to prospectively assess the utility of the Lab-score in safely decreasing antibiotic prescriptions in children with FWS and to determine its diagnostic characteristics compared to common SBI biomarkers. Methods Randomized controlled trial in children 7 days to 36 months old with FWS, allocated either to the Lab-score group (Lab-score reported, blinded WBC count) or to the control group (WBC, bands and C-reactive protein determined, blinded procalcitonin and Lab-score), followed up until recovery. Demographic data, antibiotic prescription rate, admission rate and diagnostic properties of the Lab-score were analyzed. Results 271 children were analyzed. No statistically significant difference concerning antibiotic prescription rate was observed: 41.2% (54 of 131) in the Lab-score group and 42.1% (59 of 140) in the control group (p = 1.000). If recommendations based on the Lab-score had been strictly applied, a hypothetical 30.6% treatment rate would have been encountered, compared to the overall 41.7% observed rate (p = 0.0095). A Lab-score ≥3 showed the following characteristics: sensitivity 85.1% (95% CI: 76.5–93.6%), specificity 87.3% (95% CI: 82.7–91.8%), positive predictive value 68.7% (95% CI: 58.7–78.7%), negative predictive value 94.1% (95% CI: 91.5–97.9%), positive and negative likelihood ratios: 6.68 and 0.17 respectively. Area under the receiver operating characteristic curve was best for the Lab-score (0.911, 95% CI: 0.871–0.950). Discussion No difference regarding antibiotic treatment rate was observed when using the Lab-score, due to lack of adherence to the related recommendations. However, if strictly followed, a significant 26.5% reduction of antibiotic prescriptions would have been encountered. Medical education needs to be reinforced in order to observe rather than treat low-risk well-appearing children with FWS. Trial Registration ClinicalTrials.gov NCT02179398

Nasopharyngeal carriage of individual Streptococcus pneumoniae serotypes during pediatric radiologically confirmed community acquired pneumonia following PCV7 introduction in Switzerland

BackgroundCommunity-acquired pneumonia (CAP) is a serious cause of morbidity among children in developed countries. The real impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal pneumonia is difficult to assess accurately.MethodsChildren aged ≤16 years with clinical and radiological pneumonia were enrolled in a multicenter prospective study. Children aged ≤16 years admitted for a minor elective surgery was recruited as controls. Nasopharyngeal samples for PCR serotyping of S. pneumoniae were obtained in both groups. Informations on age, gender, PCV7 vaccination status, day care/school attendance, siblings, tobacco exposure were collected.ResultsIn children with CAP (n=236), 54% of the nasopharyngeal swabs were PCR-positive for S. pneumoniae compared to 32% in controls (n=105) (p=0.003). Serotype 19A was the most common pneumococcal serotype carried in children with CAP (13%) and in controls (15%). Most common serotypes were non-vaccine types (39.4% for CAP and 47.1% for controls) and serotypes included only in PCV13 (32.3% for CAP and 23.5% for controls). There was no significant difference in vaccine serotype distribution between the two groups. In fully vaccinated children with CAP, the proportion of serotypes carried only in PCV13 was higher (51.4%) than in partially vaccinated or non vaccinated children (27.6% and 28.6% respectively, p=0.037).ConclusionsTwo to 4 years following introduction of PCV7, predominant S. pneumoniae serotypes carried in children with CAP were non PCV7 serotypes, and the 6 new serotypes included in PCV13 accounted for 51.4% of carried serotypes in fully vaccinated children.

Validation of a Novel Assay to Distinguish Bacterial and Viral Infections

A novel 3-protein host-assay’s diagnostic performance for distinguishing between bacterial and viral etiologies is validated in a double-blind, investigator-driven study in febrile children. BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

Recovery position significantly associated with a reduced admission rate of children with loss of consciousness

Background Loss of consciousness (LOC) is often seen in children. The response of caregivers to a child with LOC has been poorly investigated. Potential caregivers (parents, teachers) seem to have a poor knowledge of the recovery position (RP)—that is, the position into which an unconscious child should be placed in order to protect the airway. Objectives To report the management and diagnoses of LOC in childhood, and to evaluate variables associated with an increased hospital admission rate. Methods We conducted a prospective cohort study of consecutive children aged between 0 and 18 years diagnosed with LOC at 11 paediatric emergency departments (PEDs) of 6 European countries. The enrolment period was 3 months. Data were obtained from parental interviews, PED reports and clinical examination. Results 553 children were enrolled. The most frequent final diagnoses causing LOC were seizures (n=278, 50.3%), and vasovagal syncope (n=124, 22.4%). Caregivers put the child in the RP in 145 cases (26.2%). The RP was independently associated with a significant decrease in the admission rate (aOR=0.28; 95% CI 0.17 to 0.48; p<0.0001). Conclusions Our study demonstrates for the first time that the RP may reduce the admission rate of infants with LOC. Caregivers often perform inadequate manoeuvres when a child becomes unconscious. Campaigns aiming at increasing knowledge of the RP should be promoted.

Diagnostic performance of S100B protein serum measurement in detecting intracranial injury in children with mild head trauma

Objective To assess the accuracy of S100B serum level to detect intracranial injury in children with mild traumatic brain injury. Methods A multicenter prospective cohort study was carried out in the paediatric emergency departments of three tertiary hospitals in Switzerland between January 2009 and December 2011. Participants included children aged <16 years with a mild traumatic brain injury (GCS ≥13) for whom a head CT was requested by the attending physician. Venous blood was obtained within 6 h of the trauma in all children for S100B measurement before a head CT was performed. As the S100B value was not available during the acute care period, the patients management was not altered. The main measures were protein S100B value and the CT result. Results 20/73 (27.4%) included children had an intracranial injury detected on CT. S100B receiver operating characteristics area under the curve was 0.73 (95% CI 0.60 to 0.86). With a 0.14 µg/L cut-off point, S100B reached an excellent sensitivity of 95% (95% CI 77% to 100%) and 100% (95% CI 81% to 100%) in all children and in children aged >2 years, respectively. The specificity, however, was 34% (95% CI 27% to 36%) and 37% (95% CI 30% to 37%), respectively. Conclusions S100B has an excellent sensitivity but poor specificity. It is therefore an accurate tool to help rule out an intracranial injury but cannot be used as the sole marker owing to its specificity. Used with clinical decision rules, S100B may help to reduce the number of unnecessary CT scans.

Benzodiazepines in the acute management of seizures with autonomic manifestations: anticipate complications!

The use of rescue benzodiazepines in the management of seizures is widely accepted in emergency pediatric practice. They can, however, cause severe side effects, such as respiratory depression. We describe five patients who presented with severe respiratory depression following benzodiazepine administration for seizures with autonomic manifestations. We also discuss the relationship between the complications observed in our patients and the rescue treatment. A reduction in the dosage of benzodiazepines in the setting of epileptic patients with predominant autonomic symptoms may need to be considered.

Procalcitonin measurement for detection of serious bacterial infection in febrile children: comparison between two automated immunoassays

OBJECTIVES To assess the concordance of procalcitonin values at 3 cut-off ranges in a cohort of pediatric samples presenting with fever without source, using two different automated immunoassays. DESIGN AND METHODS 65 frozen samples from children presenting with fever without source were thawed, tested on both Kryptor and VIDAS systems, and compared using a regression analysis, a Bland-Altman difference plot, and analysis of concordance at the clinically relevant cut-off points. RESULTS Kryptor and VIDAS PCT results correlated remarkably well (r=0.952), with no significant difference in the frequency distribution over the 3 cut-off ranges (p=0.1384). The strength of the agreement was good (κ=0.759) with an overall concordance of 84.6%. CONCLUSION Correlation and concordance of PCT values measured by both systems were good. This finding allows clinical implementation of both techniques with the same nominal PCT cut-off values for detection of serious bacterial infection in children presenting with fever without source.

Catheterization of the Urethra in Male Children

Urethral catheterization may be needed in a child for diagnostic purposes or for performing voiding cystourethrography or monitoring urine output in very ill or postoperative patients. This video demonstrates a diagnostic urethral catheterization in a male infant.