Sergio Manzano

Markers for bacterial infection in children with fever without source

Objectives To compare the diagnostic properties of procalcitonin (PCT), C reactive protein (CRP), total white blood cells count (WBC), absolute neutrophil count (ANC) and clinical evaluation to detect serious bacterial infection (SBI) in children with fever without source. Design Prospective cohort study. Setting Paediatric emergency department of a tertiary care hospital. Participants Children aged 1–36 months with fever and no identified source of infection. Intervention Complete blood count, blood culture, urine analysis and culture. PCT and CRP were also measured and SBI probability evaluated clinically with a visual analogue scale before disclosing tests results. Outcome measure Area under the curves (AUC) of the receiver operating characteristic curves. Results Among the 328 children included in the study, 54 (16%) were diagnosed with an SBI: 48 urinary tract infections, 4 pneumonias, 1 meningitis and 1 bacteraemia. The AUC were similar for PCT (0.82; 95% CI 0.77 to 0.86), CRP (0.88; 95% CI 0.84 to 0.91), WBC (0.81; 95% CI 0.76 to 0.85) and ANC (0.80; 95% CI 0.75 to 0.84). The only statistically significant difference was between CRP and ANC (Δ AUC 0.08; 95% CI 0.01 to 0.16). It is important to note that all the surrogate markers were statistically superior to the clinical evaluation that had an AUC of only 0.59 (95% CI 0.54 to 0.65). Conclusion The study data demonstrate that CRP, PCT, WBC and ANC had almost similar diagnostic properties and were superior to clinical evaluation in predicting SBI in children aged 1 month to 3 years.

Validity of the Canadian Paediatric Triage and Acuity Scale in a tertiary care hospital

OBJECTIVE We evaluated the validity of the Canadian Paediatric Triage and Acuity Scale (PaedCTAS) for children visiting a pediatric emergency department (ED). METHODS This was a retrospective study evaluating all children who presented to a pediatric university-affiliated ED during a 1-year period. Data were retrieved from the ED database. Information regarding triage and disposition was registered in an ED database by a clerk following patient management. In the absence of a gold standard for triage, admission to hospital, admission to pediatric intensive care unit (PICU) and length of stay (LOS) in the ED were used as surrogate markers of severity. The primary outcome measure was the correlation between triage level (from 1 to 5) and admission to hospital. The correlation between triage level and dichotomous outcomes was evaluated by a chi2 test and an analysis of variance (ANOVA) was used to evaluate the association between triage level and ED LOS. RESULTS Over the 1-year period, 58,529 patients were triaged in the ED. The proportion admitted to hospital was 63% for resuscitation (level 1), 37% for emergent (level 2), 14% for urgent (level 3), 2% for semiurgent (level 4) and 1% for nonurgent (level 5) (p < 0.001). There was also a good correlation between triage levels and LOS and admission to PICU (both p < 0.001). CONCLUSION This computerized version of PaedCTAS demonstrates a string association with admission to hospital, admission to PICU and LOS in the ED. These results suggest that PaedCTAS is a valid tool for triage of children in a pediatric ED.

Detection of Kingella kingae Osteoarticular Infections in Children by Oropharyngeal Swab PCR

OBJECTIVE: The purpose of this study was to investigate if oropharyngeal swab polymerase chain reaction (PCR) could predict osteoarticular infection (OAI) due to Kingella kingae in young children. METHODS: One hundred twenty-three consecutive children aged 6 to 48 months presenting with atraumatic osteoarticular complaints were prospectively studied. All had a clinical evaluation, imaging, and blood samples. Blood and oropharyngeal specimens were tested with a PCR assay specific for K kingae. OAI was defined as bone, joint, or blood detection of pathogenic bacteria, or MRI consistent with infection in the absence of positive microbiology. K kingae OAI was defined by blood, bone, or synovial fluid positivity for the organism by culture or PCR. RESULTS: Forty children met the OAI case definition; 30 had K kingae OAI, 1 had another organism, and 9 had no microbiologic diagnosis. All 30 oropharyngeal swabs from the K kingae case patients and 8 swabs from the 84 patients without OAI or with OAI caused by another organism were positive. The sensitivity and specificity of the oropharyngeal swab PCR assay for K kingae were 100% and 90.5%, respectively. CONCLUSIONS: Detection of K kingae DNA in oropharyngeal swabs of children with clinical findings of OAI is predictive of K kingae OAI. If these findings are replicated in other settings, detection of K kingae by oropharyngeal swab PCR could improve the recognition of OAI.

Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: A randomized controlled trial

OBJECTIVE The aim of the study was to evaluate the impact of procalcitonin (PCT) measurement on antibiotic use in children with fever without source. METHOD Children aged 1 to 36 months presenting to a pediatric emergency department (ED) with fever and no identified source of infection were eligible to be included in a randomized controlled trial. Patients were randomly assigned to 1 of 2 groups as follows: PCT+ (result revealed to the attending physician) and PCT- (result not revealed). Patients from both groups also had complete blood count, blood culture, urine analysis, and culture performed. Chest radiography or lumbar puncture could be performed if required. RESULTS Of the 384 children enrolled and equally randomized into the PCT+ and PCT- groups, 62 (16%) were diagnosed with a serious bacterial infection (urinary tract infection, pneumonia, occult bacteremia, or bacterial meningitis) by primary ED investigation. Ten were also found to be neutropenic (<500 x 10(6)/L). Of the remaining undiagnosed patients, 14 (9%) of 158 received antibiotics in the PCT+ group vs 16 (10%) of 154 in the PCT- group (Delta -2%; 95% confidence interval [CI], -8 to 5). A strategy to treat all patients with PCT of 0.5 ng/mL or greater with prophylactic antibiotic in this group of patients would have resulted in an increase in antibiotic use by 24% (95% CI, 15-33). CONCLUSION Semiquantitative PCT measurement had no impact on antibiotic use in children aged 1 to 36 months who presented with fever without source. However, a strategy to use prophylactic antibiotics in all patients with abnormal PCT results would have resulted in an increase use of antibiotics.

Interrater Agreement between Nurses for the Pediatric Canadian Triage and Acuity Scale in a Tertiary Care Center

OBJECTIVES The objective was to measure the interrater agreement between nurses assigning triage levels to children visiting a pediatric emergency departments (EDs) assisted by a computerized version of the Pediatric Canadian Triage and Acuity Scale (PedCTAS). METHODS This was a prospective cohort study evaluating children triaged from Level 2 (emergent) to Level 5 (nonurgent). A convenience sample of patients triaged during 38 shifts from April to September 2007 in a tertiary care pediatric ED was evaluated. All patients were initially triaged by regular triage nurses using a computerized version of the PedCTAS. Research nurses performed a second evaluation blinded to the first evaluation using the same triage tool. These research nurses were regular ED nurses performing extra hours for research purposes exclusively. The primary outcome measure was the interrater agreement between the two nurses as measured by the linear weighted kappa score. Secondary outcomes included the proportion of patient for which nurses did not apply the triage level suggested by Staturg (override) and agreement for these overrides. RESULTS A total of 499 patients were recruited. The overall interrater agreement was moderate (linear weighted kappa score of 0.55 [95% confidence interval {CI} = 0.48 to 0.61] and quadratic weighted kappa score of 0.61 [95% CI = 0.42 to 0.80]). There was a discrepancy of more than one level in only 10 patients (2% of the study population). Overrides occurred in 23.2 and 21.8% for regular and research triage nurses, respectively. These overrides were equally distributed between increase and decrease in triage level. CONCLUSIONS Nurses using Staturg, which is a computerized version of the PedCTAS, demonstrated moderate interrater agreement for assignment of triage level to children presenting to a pediatric ED.

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

COMPARING THE OROPHARYNGEAL COLONIZATION DENSITY OF KINGELLA KINGAE BETWEEN ASYMPTOMATIC CARRIERS AND CHILDREN WITH INVASIVE OSTEOARTICULAR INFECTIONS

Colonization of the oropharynx by Kingella kingae is currently considered to be a prerequisite for later development of invasive infections. However, the oropharyngeal K. kingae DNA bacterial load in children with osteoarticular infections caused by this microorganism is not different than that of asymptomatic carriers.

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.

Effects of amoxicillin treatment on the salivary microbiota in children with acute otitis media

Amoxicillin is a first-line antibiotic treatment for acute otitis media in children and one of the most commonly used antibiotics for human bacterial infections. We investigated changes in salivary bacterial communities among children treated with amoxicillin for acute otitis media (n = 18), using a culture-independent approach based on pyrosequencing of the V3 region of the bacterial 16S rRNA gene. The control group consisted of children with acute otitis media who were not given antibiotics (n = 15). One species-level phylotype assigned to the genus Streptococcus was identified across all (n = 99) saliva samples. Two additional species-level phylotypes from the genera Gemella and Granulicatella were shared by all (n = 45) samples of control subjects. Amoxicillin treatment resulted in reduced species richness and diversity, and a significant shift in the relative abundance of 35 taxa at different ranks from phylum to species-level phylotype. At the phylum level, prevalence of TM7 and Actinobacteria decreased at the end of treatment, whereas Proteobacteria had a higher relative abundance post-treatment. Multivariate analysis showed that samples from the same control subject taken over time intervals tended to cluster together. Among antibiotic-treated subjects, samples taken before and at the end of amoxicillin treatment formed two relatively well-separated clusters both of which greatly overlapped with samples taken about 3 weeks post-treatment. Our results point to a substantial but incomplete recovery of the salivary bacterial community from the antibiotic about 3 weeks after the end of treatment.

Oropharyngeal Kingella kingae carriage in children: characteristics and correlation with osteoarticular infections.

Background:The aim of this study was to investigate changes in oropharyngeal K. kingae carriage during the first 4 y of life, including seasonal variation and comparison of asymptomatic carriage with cases of invasive osteoarticular infections (OAI).Methods:Oropharyngeal bacterial K. kingae carriage was screened in 744 healthy children aged 7–48 mo between January 2009 and December 2012. Oropharyngeal swabs were analyzed by rt-PCR targeting the DNA of K. kingae RTX toxin, epidemiological characteristics of asymptomatic carriers and OAI case patients were recorded.Results:The carriage prevalence showed no significant difference between age groups or seasons. Compared with asymptomatic carriers, OAI cases were more likely to be aged from 7 to 12 mo (OR = 2.5; 95% CI (1.2–5.0)) and 13–24 mo (OR = 2.2; 95% CI (1.2–3.9)), and less likely over 36 mo (OR = 0.2; 95% CI (0.1–0.7)). Fewer OAI cases were identified in spring compared to asymptomatic carriers (OR = 0.3; 95% CI (0.1–0.7)), while more were detected in autumn (OR = 2.5; 95% CI (1.4–4.4)).Conclusion:Although oropharyngeal K. kingae colonization is a prerequisite for further invasive infection, this epidemiological study emphasizes that the carriage rate variations do not correlate with the variations of OAI incidence by gender, season, or age group.