Do children with uncomplicated severe acute malnutrition need antibiotics? A systematic review and meta-analysis.

Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation

Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia

BACKGROUND: Community-acquired pneumonia (CAP) is the most frequent infection-related cause of death. The reference standard to diagnose CAP is a new infiltrate on chest radiograph in the presence of recently acquired respiratory signs and symptoms. This study aims to evaluate the diagnostic and prognostic accuracy of clinical signs and symptoms and laboratory biomarkers for CAP. METHODS: 545 patients with suspected lower respiratory tract infection, admitted to the emergency department of a university hospital were included in a pre-planned post-hoc analysis of two controlled intervention trials. Baseline assessment included history, clinical examination, radiography and measurements of procalcitonin (PCT), highly sensitive C-reactive protein (hsCRP) and leukocyte count. RESULTS: Of the 545 patients, 373 had CAP, 132 other respiratory tract infections, and 40 other final diagnoses. The AUC of a clinical model including standard clinical signs and symptoms (i.e. fever, cough, sputum production, abnormal chest auscultation and dyspnea) to diagnose CAP was 0.79 [95% CI, 0.75–0.83]. This AUC was significantly improved by including PCT and hsCRP (0.92 [0.89–0.94]; p < 0.001). PCT had a higher diagnostic accuracy (AUC, 0.88 [0.84–0.93]) in differentiating CAP from other diagnoses, as compared to hsCRP (AUC, 0.76 [0.69–0.83]; p < 0.001) and total leukocyte count (AUC, 0.69 [0.62–0.77]; p < 0.001). To predict bacteremia, PCT had a higher AUC (0.85 [0.80–0.91]) as compared to hsCRP (p = 0.01), leukocyte count (p = 0.002) and elevated body temperature (p < 0.001). PCT, in contrast to hsCRP and leukocyte count, increased with increasing severity of CAP, as assessed by the pneumonia severity index (p < 0.001). CONCLUSION: PCT, and to a lesser degree hsCRP, improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms. PCT is useful in the severity assessment of CAP

Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE) : A multicentre observational study

Funding Information: This project has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No. 668303. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all research nurses for their help in collecting data, and Anda Nagle (Riga) and the Institute of Microbiology at University Medical Centre Ljubljana for their help in collecting data on antimicrobial resistance. Members of the PERFORM consortium are listed in S11 Text. Publisher Copyright: Copyright: © 2020 Hagedoorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Methods and findings Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. Conclusions In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.publishersversionPeer reviewe

Profound Depletion of HIV-1 Transcription in Patients Initiating Antiretroviral Therapy during Acute Infection

Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on cART. Thus, antiretroviral treatment initiated during the acute phase of infection prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs in peripheral blood

Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

Rapport de synthèse: Enjeux de la recherche : La pneumonie communautaire chez l'enfant est un problème de santé publique considérable. Elle est responsable de 2 millions de mort par année, 70% survenant dans les pays en voie de développement. Sous nos latitudes son incidence est de 40/1000 enfants par année, ce qui représente une morbidité importante. Deux difficultés surviennent lorsqu'on cherche à diagnostiquer une pneumonie. La première est de distinguer une pneumonie bactérienne d'une virale, particulièrement chez les petits enfants où les infections virales des voies respiratoires inférieures sont fréquentes. L'OMS a définit la pneumonie selon des critères exclusivement cliniques et une étude effectuée à Lausanne en 2000 a montré que ces critères peuvent être utilisés dans nos contrées. La seconde difficulté est de définir l'agent causal de la pneumonie, ceci pour plusieurs raisons : L'aspiration endotrachéale, seul examen fiable, ne peut être obtenue de routine chez l'enfant vu son caractère invasif, la culture des secrétions nasopharyngées reflète la flore physiologique de la sphère ORL et une bactériémie n'est présente que dans moins de 10% des pneumonies. L'étiologie de la pneumonie reste souvent inconnue, et de ce fait plusieurs enfants reçoivent des antibiotiques pour une infection non bactérienne ce qui contribue au développement de résistances. L'objectif de cette étude était d'effectuer une recherche extensive de l'agent causal de la pneumonie et de déterminer quels facteurs pourraient aider le clinicien à différencier une pneumonie virale de bactérienne, en corrélant l'étiologie avec la sévérité clinique et les marqueurs de l'inflammation. Contexte de la recherche : II s'agissait d'une étude prospective, multicentrique, incluant les enfants âgés de 2 mois à 5 ans hospitalisés pour une pneumonie, selon les critères de l'OMS, dans le service de pédiatrie de Lausanne et Genève entre mars 2003 et Décembre 2005, avant l'implantation de la vaccination antipneumococcique de routine. Chaque enfant, en plus des examens usuels, bénéficiait d'une recherche étiologique extensive : Culture virale et bactérienne, PCR (Mycoplasma Pneumoniae, Chlamydia Pneumoniae, Virus Influenza A et B, RSV A et B, Rhinovirus, Parainfluenza 1-3, enterovirus, human metapneumovirus, coronavirus OC43, E229 ; et NL 63) et détection d'AG viraux dans les sécrétions nasopharyngées ; sérologies virales et bactériennes à l'entrée et 3 semaines après la sortie (AG Influenza A et B, Parainfluenza 1,2 et 3, RSV, Adenovirus, M.Pneumoniae et S.Pneumoniae). Conclusions : Un agent pathogène a été découvert chez 86% des 99 patients retenus confirmant le fait que plus la recherche étiologique est étendue plus le pourcentage d'agent causal trouvé est élevé. Une infection bactérienne a été découverte chez 53% des patients dont 45% avaient une infection à S. Pneumoniae confirmant l'importance d'une vaccination antipneumococcique de routine. La déshydratation et les marqueurs de l'inflammation tels que la C-Reactive Protein et la Procalcitonine étaient significativement plus élevés dans les pneumonies bactériennes. Aucune corrélation n'a été trouvée entre le degré de sévérité de la pneumonie et l'étiologie. L'étude a confirmé la haute prévalence d'infections virales (67%) et de co-infection (33%) dans la pneumonie de l'enfant sans que l'on connaisse le rôle réel du virus dans la pathogenèse de la pneumonie. Perspectives : d'autres études à la suite de celle-ci devraient être effectuées en incluant les patients ambulatoires afin de déterminer, avec un collectif plus large de patient, une éventuelle corrélation entre sévérité clinique et étiologie. Abstract : Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization

Usefulness of procalcitonin and C-reactive protein rapid tests for the management of children with urinary tract infection

BACKGROUND: Urinary tract infection (UTI) is a common problem in children. Because clinical findings and commonly used blood indices are nonspecific, the distinction between lower and upper urinary tract infection cannot be made easily in this population. However, this distinction is important because renal infection can induce parenchymal scarring. The objective of this study was to determine the accuracy of procalcitonin (PCT) compared with C-reactive protein (CRP) rapid tests to predict renal involvement in children with febrile UTI. METHODS: PCT and CRP were measured in the blood of children admitted to the emergency room with fever, signs and symptoms of urinary tract infection and/or a positive urine dipstick analysis. Renal parenchymal involvement was assessed by a 99mTc-labeled dimercaptosuccinic acid renal scan in the acute phase of infection in all children. Sensitivity, specificity and likelihood ratios were determined for both tests. RESULTS: Fifty-four children with a proven urinary tract infection were enrolled: 63% had renal involvement; and 37% had infection restricted to the lower urinary tract. No difference was found for age, sex and total white blood cell count between the groups. The calculated likelihood ratios of procalcitonin and C-reactive protein rapid tests were between 3.8 and 7 and 1.5 and 2.8, respectively. A positive PCT value predicted renal involvement in 87 to 92% of children with febrile UTI, compared with 44 to 83% using CRP values. CONCLUSIONS: A rapid determination of procalcitonin concentration could be useful for the management of children with febrile UTI in the emergency room

A three-step diagnosis of pediatric pneumonia at the emergency department using clinical predictors, C-reactive protein, and pneumococcal PCR.

Recommendations for the management of community-acquired pneumonia (CAP) advocate that, in the absence of the clinical and laboratory findings typical of bacterial CAP, antibiotics are not required. However, the true value of the clinical and laboratory predictors of pediatric CAP still needs to be assessed. This prospective cohort study in three emergency departments enrolled 142 children with radiological pneumonia. Pneumonia with lung consolidation was the primary endpoint; complicated pneumonia (bacteremia, empyema, or pleural effusion) was the secondary endpoint. We showed that three clinical signs (unilateral hypoventilation, grunting, and absence of wheezing), elevated procalcitonin (PCT), C-reactive protein (CRP), negative nasopharyngeal viral PCR, or positive blood pneumococcal PCR (P-PCR) were significantly associated with both pneumonia with consolidation and complicated pneumonia. Children with negative clinical signs and low CRP values had a low probability of having pneumonia with consolidation (13%) or complicated pneumonia (6%). Associating the three clinical signs, CRP &gt;80 mg/L and a positive P-PCR ruled in the diagnosis of complicated pneumonia with a positive predictive value of 75%. A model incorporating clinical signs and laboratory markers can effectively assess the risk of having pneumonia. Children with negative clinical signs and low CRP are at a low risk of having pneumonia. For children with positive clinical signs and high CRP, a positive blood pneumococcal PCR can more accurately confirm the diagnosis of pneumonia. What is Known: • Distinguishing between bacterial and viral pneumonia in children is challenging. • Reducing the inappropriate use of antibiotics is a priority. What is New: • Children with negative clinical signs and low C-reactive protein (CRP) values have a low probability of having pneumonia. • Children with high CRP values can be tested using a pneumococcal PCR to rule in the diagnosis of pneumonia with a high positive predictive value

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

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