Construction of a diagnostic prediction model of severe bacterial infection in febrile infants under 3 months old

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the selection of hospital admissions for the study." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sebastián Tornero Patricio, Liliana Charris-Castro, Mercedes Granero Asencio, Antonio Daponte Codina" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Sebastián" "apellidos" => "Tornero Patricio" ] 1 => array:2 [ "nombre" => "Liliana" "apellidos" => "Charris-Castro" ] 2 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Granero Asencio" ] 3 => array:2 [ "nombre" => "Antonio" "apellidos" => "Daponte Codina" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301953?idApp=UINPBA00005H" "url" => "/23412879/0000008700000006/v1_201711281541/S2341287917301953/v1_201711281541/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Construction of a diagnostic prediction model of severe bacterial infection in febrile infants under 3 months old" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "330" "paginaFinal" => "336" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Enrique Villalobos Pinto, Marciano Sánchez-Bayle" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Enrique" "apellidos" => "Villalobos Pinto" "email" => array:1 [ 0 => "evillalobospinto@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Marciano" "apellidos" => "Sánchez-Bayle" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Pediatría Hospitalaria, Servicio de Pediatría, Hospital Infantil Universitario Niño Jesús, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Creación de un modelo probabilístico de diagnóstico de infección bacteriana grave en lactantes febriles de 0 a 3 meses de vida" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1891 "Ancho" => 1621 "Tamanyo" => 125191 ] ] "descripcion" => array:1 [ "en" => "Comparative ROC curve for SBI (cut-off point, 80)." ] ] ] "textoCompleto" => "IntroductionFever is one of the main reasons for paediatric medical visits, accounting for 10–20% of emergency department visits.<a class="elsevierStyleCrossRef" href="#bib0090">1</a>In the field of paediatrics, fever is of greater significance due to the particular characteristics of the patients, the frequent nonspecificity of presenting symptoms in severe infections, and the anxiety that it produces in families and even in health professionals. These factors grow exponentially in young infants, especially those aged less than 3 months—the focus of our study—in who the diagnosis of a potential severe bacterial infection has more serious therapeutic and prognostic implications.Fever is usually a manifestation of infection, but in infants aged less than 3 months,<a class="elsevierStyleCrossRef" href="#bib0090">1</a> non-infectious aetiologies are more frequent and clinical diagnosis is usually challenging. Fever in these patients tends to be milder, but its presence may be a manifestation of severe disease. We ought to pay particular attention to the subset constituted by newborns (aged less than 4 weeks), who are considered a high-risk group, as up to 1/8 of those presenting with fever may have a severe bacterial infection (SBI). The most frequent causative agents in this age group are β-haemolytic group B streptococci (Streptococcus agalactiae), Enterobacter species (especially Escherichia coli) and Listeria monocytogenes.The primary objective of our study was to develop an index for the prediction of SBI in infants aged less than 3 months with fever of unknown origin, including clinical features and laboratory tests for acute phase reactants. Furthermore, we sought to establish the ideal cut-off point after which it would be possible to recommend antibiotic treatment fairly reliably and advance the appropriate use of empiric antibiotherapy.Participants and methodsWe conducted a prospective study of 5 years’ duration in infants aged 0 to 3 months that visited the emergency department with fever of unknown origin of 38°C or higher who, following emergency department protocols based on the recommendations of the Asociación Española de Pediatría (Spanish Association of Paediatrics), underwent microbiological testing and were admitted to hospital. We defined fever without source of short duration as fever whose aetiology remained unknown after a careful history taking and physical examination (PE) and with onset in the past 72h. In adherence with clinical protocols, all patients with a diagnosis of SBI received antibiotic treatment.A complete blood count with measurement of C-reactive protein (CRP) and procalcitonin (PCT) levels and collection of samples for microbiological testing—blood culture, urine culture (catheter specimen) and stool culture (in case of gastrointestinal manifestations)—were performed in all patients, and analysis of cerebrospinal fluid (following protocol) in 302 patients (43.01%).We considered the following to be SBIs<a class="elsevierStyleCrossRef" href="#bib0090">1</a>: urinary tract infection, occult bacteraemia, meningitis, pneumonia, bacterial gastroenteritis, septic arthritis, osteomyelitis and soft tissue infection.We also evaluated the original Rochester criteria with the addition of laboratory parameters, assigning one point for each of the laboratory values that were fulfilled and also one point for meeting the criteria established for the anamnesis and the PE.The Rochester criteria were the following:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Temperature≥38°C.</li><li class="elsevierStyleListItem" id="lsti0010">2.Anamnesis:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">a.Born at term.</li><li class="elsevierStyleListItem" id="lsti0020">b.Did not receive perinatal antibiotherapy.</li><li class="elsevierStyleListItem" id="lsti0025">c.Has no underlying disease.</li><li class="elsevierStyleListItem" id="lsti0030">d.Was not hospitalised longer than the mother.</li></ul></li><li class="elsevierStyleListItem" id="lsti0035">3.PE: good general health, with no signs of focal infection.</li><li class="elsevierStyleListItem" id="lsti0040">4.Laboratory values:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045">a.White blood cell (WBC) count: 5000–15,000/mm3.</li><li class="elsevierStyleListItem" id="lsti0050">b.Neutrophil count<1500.</li><li class="elsevierStyleListItem" id="lsti0055">c.Urine sediment with≤10WBC/hpf.</li></ul></li></ul>We established the following exclusion criteria:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsit0125">–Heart disease.</li><li class="elsevierStyleListItem" id="lsti0060">–Primary or secondary immunodeficiency.</li><li class="elsevierStyleListItem" id="lsti0065">–Lack of laboratory data (62 patients).</li></ul>We used SPSS for Windows, version 15.0. We summarised the results of quantitative variables as means and standard deviations, and of qualitative variables as percentages. Differences in quantitative variables were assessed by means of the parametric Student t test or the nonparametric Mann–Whitney test after checking the normality assumption with the Kolmogorov–Smirnov test. We analysed contingency tables for qualitative variables by means of the chi square test. We defined statistical significance as a p-value of less than 0.05.The association of the variables under study was assessed by means of binary logistic regression, with the dependent variable being the presence or absence of a positive culture, SBI or sepsis-meningitis. We used a backward elimination strategy, starting with a full model that included age, meeting the Rochester criteria, WBC and neutrophil counts and CRP and PCT levels, and then removing independent variables whose coefficient of regression corresponded to a p-value of less than 0.05 while retaining confounding variables in the model. We also analysed ROC curves for the final logistic regression models.We excluded the presence of collinearity by analysing condition indices and variance inflation factors.We calculated the sensitivity (Sen), specificity (Spe), positive likelihood ratio (LR+) and negative likelihood ratio (LR−) with their 95% confidence intervals (CIs) using the online software Interactive Statistical Calculation available at <a href="http://www.statpages.org/ctab22.html">http://www.statpages.org/ctab22.html</a>.ResultsWe included 702 infants, 328 of who were male (46.72%). There were positive culture results in 145 patients; 115 corresponded to urinary tract infections, followed in frequency by sepsis (n=20), meningitis (n=6) and invasive diarrhoea caused by Salmonella (n=3).Among the SBIs, we also found 21 cases of pneumonia, 13 of cellulitis and 2 of omphalitis.Following are the percentages of positive cultures, cases of sepsis-meningitis and cases of SBI with the corresponding 95% CIs:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0070">–Positive culture: 20.66% (17.82–23.81%).</li><li class="elsevierStyleListItem" id="lsti0075">–Sepsis: 2.85% (1.83–4.39%)</li><li class="elsevierStyleListItem" id="lsti0080">–Meningitis: 0.85% (0.35–1.90%).</li><li class="elsevierStyleListItem" id="lsti0085">–Sepsis-meningitis: 3.70% (2.52–5.39%).</li><li class="elsevierStyleListItem" id="lsti0090">–SBI: 22.39% (19.97–26.19%).</li></ul>The most frequent pathogen was E. coli, detected in 62.75% of cultures (n=91, 6 as the aetiological agent in meningitis) and 73.9% of urinary infections (n=85), followed by Enterococcus species, found in 15 patients. S. agalactiae was found in 35% of sepsis cases (n=7) and 20% of meningitis cases (n=1). Streptococcus pneumoniae accounted for 25% of sepsis cases (n=5) and 40% of meningitis cases (n=2).<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents data for epidemiological variables and the documented blood test values.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> presents the age and laboratory parameters by positive or negative result of culture, with a statistically significant increase in laboratory values associated with the former (P<.0001).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows an equivalent comparison based on the presence or absence of SBI, with similar results.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> presents the results of binary logistic regression for positive culture, SBI or diagnosis of sepsis and/or meningitis, which were statistically significant for the following: CRP and PCT, laboratory parameters, and a score of less than 4 in the Rochester criteria. The model was less reliable for sepsis and/or meningitis, with a noticeably smaller area under the curve (AUC) and larger p-values for sepsis and/or meningitis.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>When it came to the Rochester criteria, we obtained an AUC for SBI (corresponding to not meeting the criteria) of 0.69 (0.573–0.809), with a Sen of 0.917 (0.870–0.950), a Spe of 0.820 (0.804–0.831) and a LR− of 0.966 (0.947–0.980) for meeting fewer than 4 criteria.As supplementary information, we present the Sen and Spe for other cut-off points with their 95% confidence intervals in the predictive model for SBI:SBI 50: Sen, 0.75 (0.68–0.80); Spe, 0.66 (0.64–0.68)SBI 75: Sen, 0.86 (0.80–0.90); Spe, 0.68 (0.66–0.69)Thus, the model can be summarised into the following probability formulas:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0095">1.“The probability of obtaining a positive culture (pC+) is obtained by adding a constant (0.024), to the obtained CRP value×1.058, the obtained PCT value×1.087, and 36.097 if the score for the Rochester criteria is <4″ (pC+=0.024+CRP×1.058+PCT×1087+36.1 [R<4]).</li><li class="elsevierStyleListItem" id="lsti0100">2.“The probability of having a SBI is obtained by adding a constant (0.017) to the obtained CRP value×1.124, the obtained PCT value×1.128, and 67.701 if the score for the Rochester criteria is <4″ (pSBI=0.017+CRP×1.124+PCT×1.128+67.701 (R<4]).</li></ul><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> presents the cut-off points for the SBI and positive culture models, with a LR− of 0.10 and 0.17 for the cut-off points of 80 and 25, respectively, which indicate that there is a very low probability of obtaining a false negative (FN) with these models. The NPVs for SBI and positive culture were 0.982 (0.964–0.992) and 0.987 (0.970–0.995), respectively.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia><a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a> compare our model with the obtained laboratory values, and we did not find statistically significant differences in the model when we divided the sample into newborns and infants aged more than 1 month.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Thus, for positive culture (cut-off point, 25):<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0105">–<1month: AUC, 0.862, with a standard error of 0.041; 95% CI, 0.782–0.943.</li><li class="elsevierStyleListItem" id="lsti0110">–>1month: AUC: 0.832, with a standard error of 0.043; 95% CI, 0.798–0.914.</li></ul>For SBI (cut-off point, 80):<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0115">–<1month: AUC, 0.832, with a standard error of 0.043; 95% CI, 0.747–0.916.</li><li class="elsevierStyleListItem" id="lsti0120">–>1month: AUC, 0.837, with a standard error of 0.032; 95% CI, 0.775–0.899.</li></ul>Using this model, 56.26% of the patients in the sample would not receive unnecessary antibiotic treatment applying the established threshold for SBI, and 66.52% would not receive it applying the threshold for positive culture.DiscussionIn our sample, we found a prevalence of SBI of 22.64%, with a proportion of positive cultures of 20.65%; furthermore, the laboratory parameters showed significantly higher WBC and total neutrophil counts and CRP and PCT values in children with positive cultures and SBI.A systematic review of 14 studies<a class="elsevierStyleCrossRef" href="#bib0095">2</a> found a mean prevalence of 20.5% (4.5–29.3%).Analysing the laboratory parameters, we found that patients with SBI in our study (n=180) had a mean WBC count of more than 15000 (15982), a slightly lower mean neutrophil count (8139), CRP values of approximately 5mg/dL (4.96) and PCT values greater than 2ng/mL (2.23). We ought to remember that the AUC for the SBI model ranged between 0.66 for the WBC count and 0.73 for CRP.Other studies, such as the one by Cuello García et al.,<a class="elsevierStyleCrossRef" href="#bib0100">3</a> with AUCs of 0.6 for neutrophils, 0.55 for the total WBC count and 0.71 for CRP, report values slightly below those obtained in our study. Their study did not analyse the levels of PCT. Yet others have found AUC values greater than those found in our study, such as that by Fernández López<a class="elsevierStyleCrossRef" href="#bib0105">4</a> et al. from 2003, with AUCs of 0.95 for PCT and 0.81 for CRP, or the study of Andreola et al.,<a class="elsevierStyleCrossRef" href="#bib0110">5</a> with AUCs of 0.82, 0.85, 0.81 and 0.74 for PCT, CRP, total WBC count and neutrophils. Another study published in 2008 by Maniaci et al.<a class="elsevierStyleCrossRef" href="#bib0115">6</a> reported an AUC of 0.66 for the WBC count (the same as ours) and AUCs of 0.74 for the neutrophil count and 0.82 for PCT, greater than those obtained in our study.A validation study of a laboratory risk index score carried out by Galetto-Lacour et al. in 2010<a class="elsevierStyleCrossRef" href="#bib0120">7</a> found that the score varied with PCT values above or below 0.5 and 2, CRP values above or below 40 and 100, and positive versus negative urine dipstick results. This study (n=106 infants aged less than 3 months) obtained an AUC of 0.91 for the index score, which was greater than the AUCs obtained for PCT, CRP or WBC individually, which were of 0.84, 0.86 and 0.71, respectively.This last study, which is of great relevance, suggested that the combination of parameters achieved a greater diagnostic accuracy.Analysing the Rochester criteria in our sample, we found that 165 patients out of the 180 in whom a SBI was detected did not meet the low risk criteria, with the sensitivity, specificity, NPV and AUC reported above. When we analysed the sepsis-meningitis subset separately, we obtained a Sen of 63.63%, a Spe of 63.97% and a NPV of 98.19%. These figures, which were quite good for SBI overall, could certainly be improved in this subset, especially when it comes to sensitivity for ruling out sepsis-meningitis. The low number of these patients in our sample may explain the inaccuracy of the data. Thus, in the low-risk group, the risk of having a SBI (FN) was 2.13% and the risk of having sepsis-meningitis was 1.80%, whereas in the high-risk group, the risk of presenting a SBI (true positive) was 65.63% and the risk of having sepsis-meningitis was 5.4%.Our model did not exclude any patients with SBI, perhaps at the price of a decreased specificity, however, the model is enriched by taking into account laboratory parameters that were not originally included in the Rochester criteria.Our findings diverge from those of other published studies, the classic one being that by Baraff et al.,<a class="elsevierStyleCrossRef" href="#bib0125">8</a> which found a similar risk of SBI and sepsis-meningitis in the low-risk group (2.6% and 1.3%), but a much lower risk of SBI (24.3%) in the high-risk group, approximately 40% smaller than the risk we found. In different prospective studies that used these criteria, alone or combined with the Philadelphia criteria, the prevalence of SBI in the high-risk group ranged from 12.3% to 33.9% of patients,<a class="elsevierStyleCrossRefs" href="#bib0130">9–12</a> which also stood in contrast to our percentage of 65.63%. These same studies, however, have reported similar risk percentages in the low-risk group, with a variability that ranged between 0% and 5.97%. A literature review from 2010 that analysed all the studies published on the subject, a total of 21,<a class="elsevierStyleCrossRef" href="#bib0150">13</a> concluded that the estimated risk of SBI in the high-risk group ranged between 19.8% and 23.8% (in prospective versus retrospective studies), while it ranged between 0.67% and 2.71% in the low-risk group. These data are largely consistent with the low-risk group in our study, but not the high-risk group. This discrepancy may be explained by the populations under study, as our sample consisted of hospitalised patients, whereas these other studies were conducted in the general population.In our multivariate analysis, only the CRP and PCT values and a score of less than 4 for the Rochester criteria remained in the models for the presence of positive culture, SBI or diagnosis of sepsis and/or meningitis, although in the latter model both the R2 (0.234) and the AUC (0.650) were mediocre. Using the results obtained through logistic regression, we calculated the Sen, Spe, odds ratio (OR), LR+ and LR− for the cut-off points of 25 (for positive culture) and 80 (for SBI).There have been several previous “attempts” to establish a predictive model for SBI: we ought to mention a study published in 1991 by Downs et al.<a class="elsevierStyleCrossRef" href="#bib0155">14</a> in children aged 2–24 months which, based on the clinical status of the patient and the WBC count (greater or less than 15000 cells per field), concluded that the best approach to the management of febrile infants considered at risk was empiric antibiotherapy in all. It is worth noting that while this study mentioned factors such as the erythrocyte sedimentation rate or the level of CRP it did not take them into account, and that patients without manifestations of meningitis were excluded from the analysis. Along the same lines, in a review published 12 years later in the British Medical Journal,<a class="elsevierStyleCrossRef" href="#bib0160">15</a> Brook advocated a conservative approach to the management of febrile infants aged less than 3 months, proposing that they be admitted to hospital and be given empiric antibiotic treatment pending the results of bacterial culture, although the author already remarked on the disadvantages of hospitalisation, untoward comorbidity and side effects of antibiotherapy that may result from this approach. One year later, the American Medical Association<a class="elsevierStyleCrossRef" href="#bib0165">16</a> published a study conducted in 3066 febrile infants aged less than 3 months, a fairly large sample, analysing the role of clinical scales and the WBC count in the management of these patients. Unlike our study, it included patients that had been discharged from hospital, and concluded that the parameters associated most strongly to SBI were age and clinical appearance, without taking into account CRP or PCT levels. Continuing our review of models published in the literature that preceded the one presented here, we should probably comment on the one that has the most similarities with ours, which corresponds to the study by Bachur and Harper<a class="elsevierStyleCrossRef" href="#bib0170">17</a> published in 2001. This study included in the analysis 5279 infants aged less than 3 months that sought emergency care for fever. It did also not take into account CRP or PCT values, but it did consider the WBC count and results of urine analysis. The proportion of SBI that they reported was considerably lower compared to ours: 7% compared to 22.64%, the prevalence calculated in our series, which was similar to the prevalence found in the aforementioned study by Brook, although it was not specified whether cases of pneumonia were included in the analysis. The pathogen detected most frequently was group B streptococcus, contrary to our series, in which E. coli was most frequent; their sensitivity was slightly lower than ours (82% vs 87%), while they obtained a higher specificity (76% vs 68.3%), which probably has to do with the cut-off point that we established. Their reported OR of 12 was also lower than the one we obtained, which was 14.41.Our model also achieved a higher diagnostic accuracy than that achieved with the individual use of WBC count, neutrophil count, CRP or PCT. We did not find differences in the applicability of the model to newborns versus infants aged more than 1 month, and we could establish with a high degree of certainty the probability of obtaining positive culture results in our patients (except in cases of nonbacteraemic pneumonia) through the application of the alternative formula for positive culture.The high NPV and the low negative likelihood ratios (0.10 and 0.17, respectively, see <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>), along with the high impact of this model in our sample, provide reasonable grounds to decide against initiating antibiotic treatment in patients identified as being at low risk, although this requires subsequent validation. Furthermore, our model would only fail to classify 0.99% of patients with SBI and 0.71% of patients with positive cultures correctly.We expect and hope that this model will be useful in everyday clinical practice and as a basis for future studies.ConclusionsAfter conducting this study, we can reasonably conclude that it is possible to develop a predictive index for SBI (SBIPI) and for positive culture results (PCPI) for infants aged less than 3 months with fever of unknown origin integrating clinical and laboratory findings. Both indices were able to reliably diagnose most cases of SBI in our sample with the established cut-off points, with a LR− very close to zero.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres947369" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec919837" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres947370" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec919836" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Participants and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-04-07" "fechaAceptado" => "2017-02-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec919837" "palabras" => array:7 [ 0 => "Serious bacterial infection" 1 => "Fever" 2 => "Positive cultures" 3 => "Less than 3 months old" 4 => "C-reactive protein" 5 => "Procalcitonin" 6 => "Rochester criteria" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec919836" "palabras" => array:7 [ 0 => "Infección bacteriana grave" 1 => "Fiebre" 2 => "Cultivos positivos" 3 => "Menores de 3 meses" 4 => "Proteína C reactiva" 5 => "Procalcitonina" 6 => "Rochester" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionFever is a common cause of paediatric admissions in emergency departments. An aetiological diagnosis is difficult to obtain in those less than 3 months of age, as they tend to have a higher rate of serious bacterial infection (SBI). The aim of this study is to find a predictor index of SBI in children under 3 months old with fever of unknown origin. MethodsA study was conducted on all children under 3 months of age with fever admitted to hospital, with additional tests being performed according to the clinical protocol. Rochester criteria for identifying febrile infants at low risk for SBI were also analysed.A predictive model for SBI and positive cultures was designed, including the following variables in the maximum model: C-reactive protein (CRP), procalcitonin (PCT), and meeting not less than four of the Rochester criteria. ResultsA total of 702 subjects were included, of which 22.64% had an SBI and 20.65% had positive cultures. Children who had SBI and a positive culture showed higher values of white cells, total neutrophils, CRP and PCT. A statistical significance was observed with less than 4 Rochester criteria, CRP and PCT levels, an SBI (area under the curve [AUC] 0.877), or for positive cultures (AUC 0.888). Using regression analysis a predictive index was calculated for SBI or a positive culture, with a sensitivity of 87.7 and 91%, a specificity of 70.1 and 87.7%, an LR+ of 2.93 and 3.62, and a LR− of 0.17 and 0.10, respectively. ConclusionsThe predictive models are valid and slightly improve the validity of the Rochester criteria for positive culture in children less than 3 months admitted with fever." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa fiebre es motivo frecuente de consulta pediátrica y en menores de 3 meses su diagnóstico etiológico es difícil, siendo un grupo de pacientes con mayor tasa de infección bacteriana grave (IBG). Nuestro objetivo es encontrar un modelo predictivo de IBG en menores de 3 meses con fiebre sin foco. MétodosSe estudió a los niños menores de 3 meses con fiebre sin foco ingresados, realizándose pruebas complementarias según protocolo clínico. Se analizaron además los criterios de Rochester de bajo grado de IBG. Se diseñó un modelo predictivo de IBG y cultivo positivo, incluyendo las siguientes variables en el modelo máximo: proteína C reactiva (PCR), procalcitonina (PCT) y cumplimiento o no de menos de 4 criterios de Rochester. ResultadosSe incluyó a 702 sujetos; el 22,64% presentaba IBG y el 20,65% cultivos positivos. Los que presentaban IBG y cultivo positivo presentaron más leucocitos, neutrófilos totales, PCR y PCT. Se obtuvieron significación estadística en puntuación de Rochester menor de 4 y valores de PCR y PCT para IBG (área bajo la curva [ABC] 0,877) y para cultivos positivos (ABC 0,888). Con la regresión se obtuvieron unas fórmulas de predicción de IBG y cultivo positivo con sensibilidad del 87,7 y el 91%, especificidad del 70,1 y el 87,7%, CPP de 2,93 y 3,62 y CPN de 0,17 y 0,10, respectivamente. ConclusionesLos modelos predictivos son válidos y mejoran discretamente la validez de los criterios de Rochester para cultivo positivo en menores de 3 meses ingresados con fiebre." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Villalobos Pinto E, Sánchez-Bayle M. Creación de un modelo probabilístico de diagnóstico de infección bacteriana grave en lactantes febriles de 0 a 3 meses de vida. An Pediatr (Barc). 2017;87:330–336." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1897 "Ancho" => 1631 "Tamanyo" => 129497 ] ] "descripcion" => array:1 [ "en" => "Comparative ROC curve for positive culture (cut-off point: 25)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1891 "Ancho" => 1621 "Tamanyo" => 125191 ] ] "descripcion" => array:1 [ "en" => "Comparative ROC curve for SBI (cut-off point, 80)." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Minimum \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Maximum \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard deviation \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">702 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.3375 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.76569 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">675 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13035 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6576 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutrophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">375 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">500 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5820 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4240 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">641 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.6694 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.86526 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">701 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.9655 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.99245 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604457.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Epidemiological and blood test data." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive culture \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Negative culture \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.40 (0.83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.31 (0.74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15584 (6.593) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12356 (6409) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutrophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7664 (3753) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5447 (4174) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.82 (5.56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.06 (2.96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.47 (7.59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.57 (2.09) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604453.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Age and laboratory parameters by result of culture: mean (standard deviation)." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SBI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No SBI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.44 (0.80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.29 (0.74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.046 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15982 (6980) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11996 (6103) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutrophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8139 (5190) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5130 (3646) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.96 (5.40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.83 (2.68) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.23 (6.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.52 (2.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604456.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Age and laboratory values by presence of SBI: mean (standard deviation)." ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "pC+=0.024+CRP×1.058+PCT×1.087+36.1 (R<4).pSBI=0.017+CRP×1.124+PCT×1.128+67.701 (R<4)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive culture \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SBI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sepsis or meningitis \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.058 (1–1.118) P=.049 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.124 (1.047–1.207) P=.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.175 (1.079–1.216) P<.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.087 (0.996–1.187) P=.063 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.128 (1.015–1.254) P=.025 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.106 (0.994–1.118) P=.066 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rochester < 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36.097 (18.58–70.09) P<.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67.701 (33.41–137.15) P<.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36.09 (18.58–70.09) P=.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">R2 of the model \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.505 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.632 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.234 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Significance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P<.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P=.005 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Area under t \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.888 (0.859–0.916) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.877 (0.850–0.904) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.650 (0.573–0.727) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604455.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of binary logistic regression: coefficient (confidence interval)." ] ] 6 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Comparison of the models for SBI and positive culture: statistics." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive culture \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SBI \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cut-off point \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sensitivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.9 (85–95) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87.7 (80–92) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Specificity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74.7 (73–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.1 (68–71) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">OR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.29 (16.34–69.76) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.70 (9.15–30.93) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive likelihood ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.62 (3.19–3.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.93 (2.56–3.21) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Negative likelihood ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.10 (0.05–0.19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17 (0.10–0.20) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1604454.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Value of diagnostic tests for the positive culture and SBI models, with their corresponding cut-off points." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0090" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fiebre sin foco" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Rodrigo Gonzalo de Liria" 1 => "M. Méndez Hernández" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:3 [ "titulo" => "Protocolos diagnóstico-terapéuticos de la AEP: infectología pediátrica" "edicion" => "3a ed." "serieFecha" => "2011" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0095" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Van der Bruel" 1 => "M.J. Thompson" 2 => "T. Haj-Hassan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Br Med J" "fecha" => "2011" "volumen" => "342" "paginaInicial" => "d3082" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0100" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leucocitos en sangre, eritrosedimentación y proteína C reactiva en pacientes de 0 a 90 días de edad con fiebre sin focalización" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.A. Cuello García" 1 => "L. Tamez Gómez" 2 => "J. Valdez Ceballos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "An Pediatr (Barc)" "fecha" => "2008" "volumen" => "68" "paginaInicial" => "103" "paginaFinal" => "109" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0105" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants: results of a multicenter study and utility of a rapid qualitative test for this marker" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "and the Spanish Society of Pediatric Emergencies" "etal" => false "autores" => array:4 [ 0 => "A. Fernández López" 1 => "C. Luaces Cubells" 2 => "J.J. García García" 3 => "J. 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Construction of a diagnostic prediction model of severe bacterial infection in febrile infants under 3 months old

Creación de un modelo probabilístico de diagnóstico de infección bacteriana grave en lactantes febriles de 0 a 3 meses de vida

Enrique Villalobos Pinto

Corresponding author

evillalobospinto@gmail.com

Corresponding author.

, Marciano Sánchez-Bayle

Sección de Pediatría Hospitalaria, Servicio de Pediatría, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

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    "titulo" => "Construction of a diagnostic prediction model of severe bacterial infection in febrile infants under 3 months old"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparative ROC curve for SBI &#40;cut-off point&#44; 80&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Fever is one of the main reasons for paediatric medical visits&#44; accounting for 10&#8211;20&#37; of emergency department visits&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the field of paediatrics&#44; fever is of greater significance due to the particular characteristics of the patients&#44; the frequent nonspecificity of presenting symptoms in severe infections&#44; and the anxiety that it produces in families and even in health professionals&#46; These factors grow exponentially in young infants&#44; especially those aged less than 3 months&#8212;the focus of our study&#8212;in who the diagnosis of a potential severe bacterial infection has more serious therapeutic and prognostic implications&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Fever is usually a manifestation of infection&#44; but in infants <span class="elsevierStyleItalic">aged less than 3 months</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> non-infectious aetiologies are more frequent and clinical diagnosis is usually challenging&#46; Fever in these patients tends to be milder&#44; but its presence may be a manifestation of severe disease&#46; We ought to pay particular attention to the subset constituted by newborns &#40;aged less than 4 weeks&#41;&#44; who are considered a high-risk group&#44; as up to 1&#47;8 of those presenting with fever may have a severe bacterial infection &#40;SBI&#41;&#46; The most frequent causative agents in this age group are &#946;-haemolytic group B streptococci &#40;<span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#41;&#44; <span class="elsevierStyleItalic">Enterobacter</span> species &#40;especially <span class="elsevierStyleItalic">Escherichia coli</span>&#41; and <span class="elsevierStyleItalic">Listeria monocytogenes</span>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The primary <span class="elsevierStyleItalic">objective</span> of our study was to develop an index for the prediction of SBI in infants aged less than 3 months with fever of unknown origin&#44; including clinical features and laboratory tests for acute phase reactants&#46; Furthermore&#44; we sought to establish the ideal cut-off point after which it would be possible to recommend antibiotic treatment fairly reliably and advance the appropriate use of empiric antibiotherapy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Participants and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a prospective study of 5 years&#8217; duration in infants aged 0 to 3 months that visited the emergency department with fever of unknown origin of 38<span class="elsevierStyleHsp" style=""></span>&#176;C or higher who&#44; following emergency department protocols based on the recommendations of the Asociaci&#243;n Espa&#241;ola de Pediatr&#237;a &#40;Spanish Association of Paediatrics&#41;&#44; underwent microbiological testing and were admitted to hospital&#46; We defined fever without source of short duration as fever whose aetiology remained unknown after a careful history taking and physical examination &#40;PE&#41; and with onset in the past 72<span class="elsevierStyleHsp" style=""></span>h&#46; In adherence with clinical protocols&#44; all patients with a diagnosis of SBI received antibiotic treatment&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A complete blood count with measurement of C-reactive protein &#40;CRP&#41; and procalcitonin &#40;PCT&#41; levels and collection of samples for microbiological testing&#8212;blood culture&#44; urine culture &#40;catheter specimen&#41; and stool culture &#40;in case of gastrointestinal manifestations&#41;&#8212;were performed in all patients&#44; and analysis of cerebrospinal fluid &#40;following protocol&#41; in 302 patients &#40;43&#46;01&#37;&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We considered the following to be SBIs<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a>&#58; urinary tract infection&#44; occult bacteraemia&#44; meningitis&#44; pneumonia&#44; bacterial gastroenteritis&#44; septic arthritis&#44; osteomyelitis and soft tissue infection&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We also evaluated the original Rochester criteria with the addition of laboratory parameters&#44; assigning one point for each of the laboratory values that were fulfilled and also one point for meeting the criteria established for the anamnesis and the PE&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The Rochester criteria were the following&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Temperature<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>38<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Anamnesis&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">a&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Born at term&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">b&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Did not receive perinatal antibiotherapy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">c&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Has no underlying disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">d&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Was not hospitalised longer than the mother&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">PE&#58; good general health&#44; with no signs of focal infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Laboratory values&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">a&#46;</span><p id="par0090" class="elsevierStylePara elsevierViewall">White blood cell &#40;WBC&#41; count&#58; 5000&#8211;15&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">b&#46;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Neutrophil count<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1500&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">c&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Urine sediment with<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>WBC&#47;hpf&#46;</p></li></ul></p></li></ul></p><p id="par0105" class="elsevierStylePara elsevierViewall">We established the following <span class="elsevierStyleItalic">exclusion criteria</span>&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsit0125"><span class="elsevierStyleLabel">&#8211;</span><p id="par0365" class="elsevierStylePara elsevierViewall">Heart disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8211;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Primary or secondary immunodeficiency&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8211;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Lack of laboratory data &#40;62 patients&#41;&#46;</p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">We used SPSS for Windows&#44; version 15&#46;0&#46; We summarised the results of quantitative variables as means and standard deviations&#44; and of qualitative variables as percentages&#46; Differences in quantitative variables were assessed by means of the parametric Student <span class="elsevierStyleItalic">t</span> test or the nonparametric Mann&#8211;Whitney test after checking the normality assumption with the Kolmogorov&#8211;Smirnov test&#46; We analysed contingency tables for qualitative variables by means of the chi square test&#46; We defined statistical significance as a <span class="elsevierStyleItalic">p</span>-value of less than 0&#46;05&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The association of the variables under study was assessed by means of binary logistic regression&#44; with the dependent variable being the presence or absence of a positive culture&#44; SBI or sepsis-meningitis&#46; We used a backward elimination strategy&#44; starting with a full model that included age&#44; meeting the Rochester criteria&#44; WBC and neutrophil counts and CRP and PCT levels&#44; and then removing independent variables whose coefficient of regression corresponded to a <span class="elsevierStyleItalic">p</span>-value of less than 0&#46;05 while retaining confounding variables in the model&#46; We also analysed ROC curves for the final logistic regression models&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We excluded the presence of collinearity by analysing condition indices and variance inflation factors&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">We calculated the sensitivity &#40;Sen&#41;&#44; specificity &#40;Spe&#41;&#44; positive likelihood ratio &#40;LR&#43;&#41; and negative likelihood ratio &#40;LR&#8722;&#41; with their 95&#37; confidence intervals &#40;CIs&#41; using the online software Interactive Statistical Calculation available at <a href="http://www.statpages.org/ctab22.html">http&#58;&#47;&#47;www&#46;statpages&#46;org&#47;ctab22&#46;html</a>&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0140" class="elsevierStylePara elsevierViewall">We included 702 infants&#44; 328 of who were male &#40;46&#46;72&#37;&#41;&#46; There were positive culture results in 145 patients&#59; 115 corresponded to urinary tract infections&#44; followed in frequency by sepsis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&#44; meningitis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; and invasive diarrhoea caused by <span class="elsevierStyleItalic">Salmonella</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Among the SBIs&#44; we also found 21 cases of pneumonia&#44; 13 of cellulitis and 2 of omphalitis&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Following are the percentages of positive cultures&#44; cases of sepsis-meningitis and cases of SBI with the corresponding 95&#37; CIs&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8211;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Positive culture&#58; 20&#46;66&#37; &#40;17&#46;82&#8211;23&#46;81&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8211;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Sepsis&#58; 2&#46;85&#37; &#40;1&#46;83&#8211;4&#46;39&#37;&#41;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8211;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Meningitis&#58; 0&#46;85&#37; &#40;0&#46;35&#8211;1&#46;90&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8211;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Sepsis-meningitis&#58; 3&#46;70&#37; &#40;2&#46;52&#8211;5&#46;39&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8211;</span><p id="par0175" class="elsevierStylePara elsevierViewall">SBI&#58; 22&#46;39&#37; &#40;19&#46;97&#8211;26&#46;19&#37;&#41;&#46;</p></li></ul></p><p id="par0180" class="elsevierStylePara elsevierViewall">The most frequent pathogen was <span class="elsevierStyleItalic">E&#46; coli</span>&#44; detected in 62&#46;75&#37; of cultures &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91&#44; 6 as the aetiological agent in meningitis&#41; and 73&#46;9&#37; of urinary infections &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>85&#41;&#44; followed by <span class="elsevierStyleItalic">Enterococcus</span> species&#44; found in 15 patients&#46; <span class="elsevierStyleItalic">S&#46; agalactiae</span> was found in 35&#37; of sepsis cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41; and 20&#37; of meningitis cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> accounted for 25&#37; of sepsis cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; and 40&#37; of meningitis cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents data for epidemiological variables and the documented blood test values&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> presents the age and laboratory parameters by positive or negative result of culture&#44; with a statistically significant increase in laboratory values associated with the former &#40;<span class="elsevierStyleItalic">P<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;</span>0001&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0195" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows an equivalent comparison based on the presence or absence of SBI&#44; with similar results&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0200" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> presents the results of binary logistic regression for positive culture&#44; SBI or diagnosis of sepsis and&#47;or meningitis&#44; which were statistically significant for the following&#58; CRP and PCT&#44; laboratory parameters&#44; and a score of less than 4 in the Rochester criteria&#46; The model was less reliable for sepsis and&#47;or meningitis&#44; with a noticeably smaller area under the curve &#40;AUC&#41; and larger <span class="elsevierStyleItalic">p</span>-values for sepsis and&#47;or meningitis&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">When it came to the Rochester criteria&#44; we obtained an AUC for SBI &#40;corresponding to not meeting the criteria&#41; of 0&#46;69 &#40;0&#46;573&#8211;0&#46;809&#41;&#44; with a Sen of 0&#46;917 &#40;0&#46;870&#8211;0&#46;950&#41;&#44; a Spe of 0&#46;820 &#40;0&#46;804&#8211;0&#46;831&#41; and a LR&#8722; of 0&#46;966 &#40;0&#46;947&#8211;0&#46;980&#41; for meeting fewer than 4 criteria&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">As supplementary information&#44; we present the Sen and Spe for other cut-off points with their 95&#37; confidence intervals in the predictive model for SBI&#58;</p><p id="par0215" class="elsevierStylePara elsevierViewall">SBI 50&#58; Sen&#44; 0&#46;75 &#40;0&#46;68&#8211;0&#46;80&#41;&#59; Spe&#44; 0&#46;66 &#40;0&#46;64&#8211;0&#46;68&#41;</p><p id="par0220" class="elsevierStylePara elsevierViewall">SBI 75&#58; Sen&#44; 0&#46;86 &#40;0&#46;80&#8211;0&#46;90&#41;&#59; Spe&#44; 0&#46;68 &#40;0&#46;66&#8211;0&#46;69&#41;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Thus&#44; the model can be summarised into the following probability formulas&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">1&#46;</span><p id="par0230" class="elsevierStylePara elsevierViewall">&#8220;The probability of obtaining a positive culture &#40;pC&#43;&#41; is obtained by adding a constant &#40;0&#46;024&#41;&#44; to the obtained CRP value<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;058&#44; the obtained PCT value<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;087&#44; and 36&#46;097 if the score for the Rochester criteria is &#60;4&#8243; &#40;pC&#43;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRP<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;058<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PCT<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1087<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>36&#46;1 &#91;<span class="elsevierStyleItalic">R</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>4&#93;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">2&#46;</span><p id="par0235" class="elsevierStylePara elsevierViewall">&#8220;The probability of having a SBI is obtained by adding a constant &#40;0&#46;017&#41; to the obtained CRP value<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;124&#44; the obtained PCT value<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;128&#44; and 67&#46;701 if the score for the Rochester criteria is &#60;4&#8243; &#40;pSBI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;017<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRP<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;124<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PCT<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;128<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>67&#46;701 &#40;<span class="elsevierStyleItalic">R</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>4&#93;&#41;&#46;</p></li></ul></p><p id="par0240" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> presents the cut-off points for the SBI and positive culture models&#44; with a LR&#8722; of 0&#46;10 and 0&#46;17 for the cut-off points of 80 and 25&#44; respectively&#44; which indicate that there is a very low probability of obtaining a false negative &#40;FN&#41; with these models&#46; The NPVs for SBI and positive culture were 0&#46;982 &#40;0&#46;964&#8211;0&#46;992&#41; and 0&#46;987 &#40;0&#46;970&#8211;0&#46;995&#41;&#44; respectively&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0245" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a> compare our model with the obtained laboratory values&#44; and we did not find statistically significant differences in the model when we divided the sample into newborns and infants aged more than 1 month&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">Thus&#44; for positive culture &#40;cut-off point&#44; 25&#41;&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8211;</span><p id="par0255" class="elsevierStylePara elsevierViewall">&#60;1<span class="elsevierStyleHsp" style=""></span>month&#58; AUC&#44; 0&#46;862&#44; with a standard error of 0&#46;041&#59; 95&#37; CI&#44; 0&#46;782&#8211;0&#46;943&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8211;</span><p id="par0260" class="elsevierStylePara elsevierViewall">&#62;1<span class="elsevierStyleHsp" style=""></span>month&#58; AUC&#58; 0&#46;832&#44; with a standard error of 0&#46;043&#59; 95&#37; CI&#44; 0&#46;798&#8211;0&#46;914&#46;</p></li></ul></p><p id="par0265" class="elsevierStylePara elsevierViewall">For SBI &#40;cut-off point&#44; 80&#41;&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8211;</span><p id="par0270" class="elsevierStylePara elsevierViewall">&#60;1<span class="elsevierStyleHsp" style=""></span>month&#58; AUC&#44; 0&#46;832&#44; with a standard error of 0&#46;043&#59; 95&#37; CI&#44; 0&#46;747&#8211;0&#46;916&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8211;</span><p id="par0275" class="elsevierStylePara elsevierViewall">&#62;1<span class="elsevierStyleHsp" style=""></span>month&#58; AUC&#44; 0&#46;837&#44; with a standard error of 0&#46;032&#59; 95&#37; CI&#44; 0&#46;775&#8211;0&#46;899&#46;</p></li></ul></p><p id="par0280" class="elsevierStylePara elsevierViewall">Using this model&#44; 56&#46;26&#37; of the patients in the sample would not receive unnecessary antibiotic treatment applying the established threshold for SBI&#44; and 66&#46;52&#37; would not receive it applying the threshold for positive culture&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0285" class="elsevierStylePara elsevierViewall">In our sample&#44; we found a prevalence of <span class="elsevierStyleItalic">SBI</span> of 22&#46;64&#37;&#44; with a proportion of <span class="elsevierStyleItalic">positive cultures</span> of 20&#46;65&#37;&#59; furthermore&#44; the laboratory parameters showed significantly higher WBC and total neutrophil counts and CRP and PCT values in children with positive cultures and SBI&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">A systematic review of 14 studies<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> found a mean prevalence of 20&#46;5&#37; &#40;4&#46;5&#8211;29&#46;3&#37;&#41;&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Analysing the <span class="elsevierStyleItalic">laboratory parameters</span>&#44; we found that patients with SBI in our study &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>180&#41; had a mean WBC count of more than 15<span class="elsevierStyleHsp" style=""></span>000 &#40;15<span class="elsevierStyleHsp" style=""></span>982&#41;&#44; a slightly lower mean neutrophil count &#40;8139&#41;&#44; CRP values of approximately 5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;4&#46;96&#41; and PCT values greater than 2<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;2&#46;23&#41;&#46; We ought to remember that the AUC for the SBI model ranged between 0&#46;66 for the WBC count and 0&#46;73 for CRP&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Other studies&#44; such as the one by Cuello Garc&#237;a et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a> with AUCs of 0&#46;6 for neutrophils&#44; 0&#46;55 for the total WBC count and 0&#46;71 for CRP&#44; report values slightly below those obtained in our study&#46; Their study did not analyse the levels of PCT&#46; Yet others have found AUC values greater than those found in our study&#44; such as that by Fern&#225;ndez L&#243;pez<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> et al&#46; from 2003&#44; with AUCs of 0&#46;95 for PCT and 0&#46;81 for CRP&#44; or the study of Andreola et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> with AUCs of 0&#46;82&#44; 0&#46;85&#44; 0&#46;81 and 0&#46;74 for PCT&#44; CRP&#44; total WBC count and neutrophils&#46; Another study published in 2008 by Maniaci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> reported an AUC of 0&#46;66 for the WBC count &#40;the same as ours&#41; and AUCs of 0&#46;74 for the neutrophil count and 0&#46;82 for PCT&#44; greater than those obtained in our study&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">A validation study of a laboratory risk index score carried out by Galetto-Lacour et al&#46; in 2010<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> found that the score varied with PCT values above or below 0&#46;5 and 2&#44; CRP values above or below 40 and 100&#44; and positive versus negative urine dipstick results&#46; This study &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>106 infants aged less than 3 months&#41; obtained an AUC of 0&#46;91 for the index score&#44; which was greater than the AUCs obtained for PCT&#44; CRP or WBC individually&#44; which were of 0&#46;84&#44; 0&#46;86 and 0&#46;71&#44; respectively&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">This last study&#44; which is of great relevance&#44; suggested that the combination of parameters achieved a greater diagnostic accuracy&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Analysing the <span class="elsevierStyleItalic">Rochester criteria</span> in our sample&#44; we found that 165 patients out of the 180 in whom a SBI was detected did not meet the low risk criteria&#44; with the sensitivity&#44; specificity&#44; NPV and AUC reported above&#46; When we analysed the sepsis-meningitis subset separately&#44; we obtained a Sen of 63&#46;63&#37;&#44; a Spe of 63&#46;97&#37; and a NPV of 98&#46;19&#37;&#46; These figures&#44; which were quite good for SBI overall&#44; could certainly be improved in this subset&#44; especially when it comes to sensitivity for ruling out sepsis-meningitis&#46; The low number of these patients in our sample may explain the inaccuracy of the data&#46; Thus&#44; in the <span class="elsevierStyleItalic">low-risk</span> group&#44; the risk of having a SBI &#40;FN&#41; was 2&#46;13&#37; and the risk of having sepsis-meningitis was 1&#46;80&#37;&#44; whereas in the <span class="elsevierStyleItalic">high-risk</span> group&#44; the risk of presenting a SBI &#40;true positive&#41; was 65&#46;63&#37; and the risk of having sepsis-meningitis was 5&#46;4&#37;&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Our model did not exclude any patients with SBI&#44; perhaps at the price of a decreased specificity&#44; however&#44; the model is enriched by taking into account laboratory parameters that were not originally included in the Rochester criteria&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Our findings diverge from those of other published studies&#44; the classic one being that by Baraff et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> which found a similar risk of SBI and sepsis-meningitis in the low-risk group &#40;2&#46;6&#37; and 1&#46;3&#37;&#41;&#44; but a much lower risk of SBI &#40;24&#46;3&#37;&#41; in the high-risk group&#44; approximately 40&#37; smaller than the risk we found&#46; In different prospective studies that used these criteria&#44; alone or combined with the Philadelphia criteria&#44; the prevalence of SBI in the high-risk group ranged from 12&#46;3&#37; to 33&#46;9&#37; of patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">9&#8211;12</span></a> which also stood in contrast to our percentage of 65&#46;63&#37;&#46; These same studies&#44; however&#44; have reported similar risk percentages in the low-risk group&#44; with a variability that ranged between 0&#37; and 5&#46;97&#37;&#46; A literature review from 2010 that analysed all the studies published on the subject&#44; a total of 21&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> concluded that the estimated risk of SBI in the high-risk group ranged between 19&#46;8&#37; and 23&#46;8&#37; &#40;in prospective versus retrospective studies&#41;&#44; while it ranged between 0&#46;67&#37; and 2&#46;71&#37; in the low-risk group&#46; These data are largely consistent with the low-risk group in our study&#44; but not the high-risk group&#46; This discrepancy may be explained by the populations under study&#44; as our sample consisted of hospitalised patients&#44; whereas these other studies were conducted in the general population&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">In our multivariate analysis&#44; only the CRP and PCT values and a score of less than 4 for the Rochester criteria remained in the models for the presence of positive culture&#44; SBI or diagnosis of sepsis and&#47;or meningitis&#44; although in the latter model both the <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span> &#40;0&#46;234&#41; and the AUC &#40;0&#46;650&#41; were mediocre&#46; Using the results obtained through logistic regression&#44; we calculated the Sen&#44; Spe&#44; odds ratio &#40;OR&#41;&#44; LR&#43; and LR&#8722; for the cut-off points of 25 &#40;for positive culture&#41; and 80 &#40;for SBI&#41;&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">There have been several previous &#8220;attempts&#8221; to establish a predictive model for SBI&#58; we ought to mention a study published in 1991 by Downs et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> in children aged 2&#8211;24 months which&#44; based on the clinical status of the patient and the WBC count &#40;greater or less than 15<span class="elsevierStyleHsp" style=""></span>000 cells per field&#41;&#44; concluded that the best approach to the management of febrile infants considered at risk was empiric antibiotherapy in all&#46; It is worth noting that while this study mentioned factors such as the erythrocyte sedimentation rate or the level of CRP it did not take them into account&#44; and that patients without manifestations of meningitis were excluded from the analysis&#46; Along the same lines&#44; in a review published 12 years later in the <span class="elsevierStyleItalic">British Medical Journal</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> Brook advocated a conservative approach to the management of febrile infants aged less than 3 months&#44; proposing that they be admitted to hospital and be given empiric antibiotic treatment pending the results of bacterial culture&#44; although the author already remarked on the disadvantages of hospitalisation&#44; untoward comorbidity and side effects of antibiotherapy that may result from this approach&#46; One year later&#44; the American Medical Association<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> published a study conducted in 3066 febrile infants aged less than 3 months&#44; a fairly large sample&#44; analysing the role of clinical scales and the WBC count in the management of these patients&#46; Unlike our study&#44; it included patients that had been discharged from hospital&#44; and concluded that the parameters associated most strongly to SBI were age and clinical appearance&#44; without taking into account CRP or PCT levels&#46; Continuing our review of models published in the literature that preceded the one presented here&#44; we should probably comment on the one that has the most similarities with ours&#44; which corresponds to the study by Bachur and Harper<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a> published in 2001&#46; This study included in the analysis 5279 infants aged less than 3 months that sought emergency care for fever&#46; It did also not take into account CRP or PCT values&#44; but it did consider the WBC count and results of urine analysis&#46; The proportion of SBI that they reported was considerably lower compared to ours&#58; 7&#37; compared to 22&#46;64&#37;&#44; the prevalence calculated in our series&#44; which was similar to the prevalence found in the aforementioned study by Brook&#44; although it was not specified whether cases of pneumonia were included in the analysis&#46; The pathogen detected most frequently was group B streptococcus&#44; contrary to our series&#44; in which <span class="elsevierStyleItalic">E&#46; coli</span> was most frequent&#59; their sensitivity was slightly lower than ours &#40;82&#37; vs 87&#37;&#41;&#44; while they obtained a higher specificity &#40;76&#37; vs 68&#46;3&#37;&#41;&#44; which probably has to do with the cut-off point that we established&#46; Their reported OR of 12 was also lower than the one we obtained&#44; which was 14&#46;41&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Our model also achieved a higher diagnostic accuracy than that achieved with the individual use of WBC count&#44; neutrophil count&#44; CRP or PCT&#46; We did not find differences in the applicability of the model to newborns versus infants aged more than 1 month&#44; and we could establish with a high degree of certainty the probability of obtaining positive culture results in our patients &#40;except in cases of nonbacteraemic pneumonia&#41; through the application of the alternative formula for positive culture&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">The high NPV and the low negative likelihood ratios &#40;0&#46;10 and 0&#46;17&#44; respectively&#44; see <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#44; along with the high impact of this model in our sample&#44; provide reasonable grounds to decide against initiating antibiotic treatment in patients identified as being at low risk&#44; although this requires subsequent validation&#46; Furthermore&#44; our model would only fail to classify 0&#46;99&#37; of patients with SBI and 0&#46;71&#37; of patients with positive cultures correctly&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">We expect and hope that this model will be useful in everyday clinical practice and as a basis for future studies&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0355" class="elsevierStylePara elsevierViewall">After conducting this study&#44; we can reasonably conclude that it is possible to develop a predictive index for SBI &#40;SBIPI&#41; and for positive culture results &#40;PCPI&#41; for infants aged less than 3 months with fever of unknown origin integrating clinical and laboratory findings&#46; Both indices were able to reliably diagnose most cases of SBI in our sample with the established cut-off points&#44; with a LR&#8722; very close to zero&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0360" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fever is a common cause of paediatric admissions in emergency departments&#46; An aetiological diagnosis is difficult to obtain in those less than 3 months of age&#44; as they tend to have a higher rate of serious bacterial infection &#40;SBI&#41;&#46; The aim of this study is to find a predictor index of SBI in children under 3 months old with fever of unknown origin&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A study was conducted on all children under 3 months of age with fever admitted to hospital&#44; with additional tests being performed according to the clinical protocol&#46; Rochester criteria for identifying febrile infants at low risk for SBI were also analysed&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A predictive model for SBI and positive cultures was designed&#44; including the following variables in the maximum model&#58; C-reactive protein &#40;CRP&#41;&#44; procalcitonin &#40;PCT&#41;&#44; and meeting not less than four of the Rochester criteria&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 702 subjects were included&#44; of which 22&#46;64&#37; had an SBI and 20&#46;65&#37; had positive cultures&#46; Children who had SBI and a positive culture showed higher values of white cells&#44; total neutrophils&#44; CRP and PCT&#46; A statistical significance was observed with less than 4 Rochester criteria&#44; CRP and PCT levels&#44; an SBI &#40;area under the curve &#91;AUC&#93; 0&#46;877&#41;&#44; or for positive cultures &#40;AUC 0&#46;888&#41;&#46; Using regression analysis a predictive index was calculated for SBI or a positive culture&#44; with a sensitivity of 87&#46;7 and 91&#37;&#44; a specificity of 70&#46;1 and 87&#46;7&#37;&#44; an LR&#43; of 2&#46;93 and 3&#46;62&#44; and a LR&#8722; of 0&#46;17 and 0&#46;10&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The predictive models are valid and slightly improve the validity of the Rochester criteria for positive culture in children less than 3 months admitted with fever&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La fiebre es motivo frecuente de consulta pedi&#225;trica y en menores de 3 meses su diagn&#243;stico etiol&#243;gico es dif&#237;cil&#44; siendo un grupo de pacientes con mayor tasa de infecci&#243;n bacteriana grave &#40;IBG&#41;&#46; Nuestro objetivo es encontrar un modelo predictivo de IBG en menores de 3 meses con fiebre sin foco&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se estudi&#243; a los ni&#241;os menores de 3 meses con fiebre sin foco ingresados&#44; realiz&#225;ndose pruebas complementarias seg&#250;n protocolo cl&#237;nico&#46; Se analizaron adem&#225;s los criterios de Rochester de bajo grado de IBG&#46; Se dise&#241;&#243; un modelo predictivo de IBG y cultivo positivo&#44; incluyendo las siguientes variables en el modelo m&#225;ximo&#58; prote&#237;na <span class="elsevierStyleSmallCaps">C</span> reactiva &#40;PCR&#41;&#44; procalcitonina &#40;PCT&#41; y cumplimiento o no de menos de 4 criterios de Rochester&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; a 702 sujetos&#59; el 22&#44;64&#37; presentaba IBG y el 20&#44;65&#37; cultivos positivos&#46; Los que presentaban IBG y cultivo positivo presentaron m&#225;s leucocitos&#44; neutr&#243;filos totales&#44; PCR y PCT&#46; Se obtuvieron significaci&#243;n estad&#237;stica en puntuaci&#243;n de Rochester menor de 4 y valores de PCR y PCT para IBG &#40;&#225;rea bajo la curva &#91;ABC&#93; 0&#44;877&#41; y para cultivos positivos &#40;ABC 0&#44;888&#41;&#46; Con la regresi&#243;n se obtuvieron unas f&#243;rmulas de predicci&#243;n de IBG y cultivo positivo con sensibilidad del 87&#44;7 y el 91&#37;&#44; especificidad del 70&#44;1 y el 87&#44;7&#37;&#44; CPP de 2&#44;93 y 3&#44;62 y CPN de 0&#44;17 y 0&#44;10&#44; respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los modelos predictivos son v&#225;lidos y mejoran discretamente la validez de los criterios de Rochester para cultivo positivo en menores de 3 meses ingresados con fiebre&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Villalobos Pinto E&#44; S&#225;nchez-Bayle M&#46; Creaci&#243;n de un modelo probabil&#237;stico de diagn&#243;stico de infecci&#243;n bacteriana grave en lactantes febriles de 0 a 3 meses de vida&#46; An Pediatr &#40;Barc&#41;&#46; 2017&#59;87&#58;330&#8211;336&#46;</p>"
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1897
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            "Tamanyo" => 129497
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparative ROC curve for positive culture &#40;cut-off point&#58; 25&#41;&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparative ROC curve for SBI &#40;cut-off point&#44; 80&#41;&#46;</p>"
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Minimum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Maximum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard deviation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">702&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;3375&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;76569&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">675&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6576&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutrophils&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">375&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29<span class="elsevierStyleHsp" style=""></span>160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5820&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4240&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">641&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;6694&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;86526&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">701&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;9655&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;99245&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Epidemiological and blood test data&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive culture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Negative culture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;40 &#40;0&#46;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;31 &#40;0&#46;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15<span class="elsevierStyleHsp" style=""></span>584 &#40;6&#46;593&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12<span class="elsevierStyleHsp" style=""></span>356 &#40;6409&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutrophils&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7664 &#40;3753&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5447 &#40;4174&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;82 &#40;5&#46;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;06 &#40;2&#46;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;47 &#40;7&#46;59&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;57 &#40;2&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;44 &#40;0&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;29 &#40;0&#46;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#46;046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11<span class="elsevierStyleHsp" style=""></span>996 &#40;6103&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutrophils&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8139 &#40;5190&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5130 &#40;3646&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;96 &#40;5&#46;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;83 &#40;2&#46;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCT &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;23 &#40;6&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;52 &#40;2&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67&#46;701 &#40;33&#46;41&#8211;137&#46;15&#41;<br><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
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                    0 => array:2 [
                      "titulo" => "Fiebre sin foco"
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                          "autores" => array:2 [
                            0 => "C&#46; Rodrigo Gonzalo de Liria"
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                        "titulo" => "Protocolos diagn&#243;stico-terap&#233;uticos de la AEP&#58; infectolog&#237;a pedi&#225;trica"
                        "edicion" => "3<span class="elsevierStyleSup">a</span> ed&#46;"
                        "serieFecha" => "2011"
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                0 => array:2 [
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                      "titulo" => "Diagnostic value of laboratory tests in identifying serious infections in febrile children&#58; systematic review"
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                        0 => array:2 [
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                          "autores" => array:3 [
                            0 => "A&#46; Van der Bruel"
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                            2 => "T&#46; Haj-Hassan"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Br Med J"
                        "fecha" => "2011"
                        "volumen" => "342"
                        "paginaInicial" => "d3082"
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                  ]
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              "etiqueta" => "3"
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                0 => array:2 [
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                      "titulo" => "Leucocitos en sangre&#44; eritrosedimentaci&#243;n y prote&#237;na C reactiva en pacientes de 0 a 90 d&#237;as de edad con fiebre sin focalizaci&#243;n"
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                          "autores" => array:3 [
                            0 => "C&#46;A&#46; Cuello Garc&#237;a"
                            1 => "L&#46; Tamez G&#243;mez"
                            2 => "J&#46; Valdez Ceballos"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "An Pediatr &#40;Barc&#41;"
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                        "volumen" => "68"
                        "paginaInicial" => "103"
                        "paginaFinal" => "109"
                      ]
                    ]
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              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants&#58; results of a multicenter study and utility of a rapid qualitative test for this marker"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "and the Spanish Society of Pediatric Emergencies"
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Fern&#225;ndez L&#243;pez"
                            1 => "C&#46; Luaces Cubells"
                            2 => "J&#46;J&#46; Garc&#237;a Garc&#237;a"
                            3 => "J&#46; Fern&#225;ndez Pou"
                          ]
                        ]
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                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1097/01.inf.0000091360.11784.21"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "2003"
                        "volumen" => "22"
                        "paginaInicial" => "895"
                        "paginaFinal" => "903"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14551491"
                            "web" => "Medline"
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                0 => array:2 [
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                      "titulo" => "Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "S&#46; Bressan"
                            2 => "S&#46; Callegaro"
                            3 => "A&#46; Liverani"
                            4 => "M&#46; Plebani"
                            5 => "L&#46; da Dalt"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2017.02.007

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Year/Month	Html	Pdf	Total

2024 November	6	10	16
2024 October	35	30	65
2024 September	50	31	81
2024 August	71	55	126
2024 July	60	27	87
2024 June	56	18	74
2024 May	54	41	95
2024 April	43	25	68
2024 March	31	23	54
2024 February	36	27	63
2024 January	37	20	57
2023 December	34	16	50
2023 November	53	24	77
2023 October	42	21	63
2023 September	25	20	45
2023 August	27	16	43
2023 July	41	26	67
2023 June	37	27	64
2023 May	39	21	60
2023 April	33	15	48
2023 March	34	30	64
2023 February	38	19	57
2023 January	21	22	43
2022 December	53	25	78
2022 November	59	41	100
2022 October	48	36	84
2022 September	25	28	53
2022 August	39	52	91
2022 July	34	35	69
2022 June	31	42	73
2022 May	40	47	87
2022 April	33	26	59
2022 March	58	43	101
2022 February	31	44	75
2022 January	36	31	67
2021 December	30	46	76
2021 November	39	42	81
2021 October	57	59	116
2021 September	39	29	68
2021 August	28	40	68
2021 July	24	39	63
2021 June	32	33	65
2021 May	39	56	95
2021 April	114	87	201
2021 March	40	44	84
2021 February	24	22	46
2021 January	37	31	68
2020 December	36	29	65
2020 November	36	17	53
2020 October	32	14	46
2020 September	35	27	62
2020 August	23	30	53
2020 July	22	42	64
2020 June	25	16	41
2020 May	30	21	51
2020 April	27	22	49
2020 March	39	15	54
2020 February	26	15	41
2020 January	29	20	49
2019 December	43	19	62
2019 November	18	12	30
2019 October	25	9	34
2019 September	23	10	33
2019 August	52	27	79
2019 July	25	34	59
2019 June	247	33	280
2019 May	196	35	231
2019 April	63	45	108
2019 March	38	34	72
2019 February	37	15	52
2019 January	48	25	73
2018 December	43	34	77
2018 November	95	32	127
2018 October	155	12	167
2018 September	57	12	69
2018 August	3	0	3
2018 July	2	0	2
2018 June	2	0	2
2018 May	3	0	3
2018 April	24	0	24
2018 March	24	0	24
2018 February	12	0	12
2018 January	16	0	16
2017 November	0	16	16

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