Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.

Rapid molecular syndromic testing for aetiological diagnosis of gastrointestinal infections and targeted antimicrobial prescription: experience from a reference paediatric hospital in Spain.

Aetiological diagnosis of gastrointestinal infections is challenging since a wide range of bacteria, parasites and viruses can be causal agents and derived clinical manifestations appear quite similar. Our aim was to evaluate contribution of the novel QIAstat-DxGastrointestinal Panel (GIP) to aetiological diagnosis of gastrointestinal infections and rational antimicrobial prescription in a reference paediatric hospital. Evaluation included comparison of diagnostic yield and agreement of results of QIAstat-Dx GIP and conventional microbiological methods. Parallel testing was performed on stool samples collected prospectively from children admitted to Sant Joan de Deu Barcelona Hospital (Spain) during the period February-March 2019. Influence of the panel test use on antimicrobial prescription was assessed using a pre-post study design. Eighty-six (68.8%) out of 125 specimens were positive by QIAstat-Dx GIP versus 44 (35.2%) positive by a composite of conventional methods (p<0.001). Global agreement of panel test results with rotavirus-adenovirus antigen detection (92.8%) and a two-step antigen/toxin and PCR-based algorithm for toxigenic Clostridioides difficile detection (87.5%) was greater than that with bacterial culture (76.0%) and parasite microscopic identification (64.3%). Panel test results orientated antimicrobial prescription changes in 18 (14.4%) patients, including antimicrobial start in 11 cases initially untreated, targeted antimicrobial prescription in 5 and discontinuation in 2 cases empirically treated. Results showed that QIAstat-Dx GIP significantly expanded aetiological diagnosis of gastrointestinal infections compared to conventional microbiological methods while orientating a more judicious use of antimicrobial drugs in hospitalised children.

Diagnostic and prognostic value of procalcitonin and mid-regional pro-adrenomedullin in septic paediatric patients.

Early diagnosis of sepsis and its severity stratification at admission is critical to improve patient outcomes and to ensure the optimal use of health care resources. In order to assess the diagnostic potential of mid-regional pro-adrenomedullin (MR-proADM) in septic paediatric patients in comparison with procalcitonin (PCT), and to evaluate the usefulness of a single early determination of MR-proADM as a stratification and severity prediction tool, a prospective observational study was conducted. Seventy-three paediatric patients with a suspicion of sepsis were included. A single blood test was carried out at initial time to analyse infection biomarkers. PCT values were significantly higher in septic patients in comparison with non-septic patients (p = 0.03) with an AUC of 0.748 (p = 0.003). Levels of MR-proADM significantly increased in patients with severe sepsis (p = 0.048), with an AUC of 0.729 (p = 0.013). MR-proADM showed a positive correlation with pSOFA, PRISM III, and PELOD-2 severity scores. Levels of MR-proADM were significantly higher in patients who required vasoactive drugs (p = 0.02) or presented renal dysfunction (p = 0.004).Conclusion: PCT appeared to be superior to MR-proADM in diagnosing sepsis. Determining MR-proADM plasma levels at the initial phase of sepsis could be a useful tool for sepsis stratification and morbidity prediction before organ failure occurs. The present results need to be assessed with larger sample size studies.What is Known:•CRP and PCT are already included in clinical practice to assess sepsis and estimate disease severity, although their sensitivity and specificity are lower than desired.•ADM is a protein that has immune and vascular modulation actions, and its blood levels are increased in adult and paediatric sepsis.•ADM is a promising tool for early diagnosis and prognostic assessment in adult sepsis.What is New:•PCT appeared to be superior to MR-proADM in diagnosing paediatric sepsis.•MR-proADM plasma levels could be a useful tool for paediatric sepsis stratification and morbidity prediction.

Procalcitonin-guided protocol decreased the antibiotic use in paediatric patients with severe bronchiolitis.

AIM: Our aim was to determine the effectiveness and safety of a procalcitonin-guided protocol to decrease antibiotic use in infants with severe bronchiolitis. METHODS: This prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin-guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010-2014 and 366 in 2015-2017. RESULTS: We recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0-100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol. CONCLUSION: The implementation of a procalcitonin-guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.

Procalcitonin to stop antibiotics after cardiovascular surgery in a pediatric intensive care unit-The PROSACAB study.

INTRODUCTION AND OBJECTIVE: Children admitted to the pediatric intensive care unit after cardiovascular surgery usually require treatment with antibiotics due to suspicion of infection. The aim of this study was to assess the effectiveness of procalcitonin in decreasing the duration of antibiotic treatment in children after cardiovascular surgery. METHODS: Prospective, interventional study carried out in a pediatric intensive care unit. Included patients under 18 years old admitted after cardiopulmonary bypass. Two groups were compared, depending on the implementation of the PCT-guided protocol to stop or de-escalate the antibiotic treatment (Group 1, 2011-2013 and group 2, 2014-2018). This new protocol was based on the decrease of the PCT value by 20% or 50% with respect to the maximum value of PCT. Primary endpoints were mortality, stewardship indication, duration of antibiotic treatment, and antibiotic-free days. RESULTS: 886 patients were recruited. There were 226 suspicions of infection (25.5%), and they were confirmed in 38 cases (16.8%). The global rate of infections was 4.3%. 102 patients received broad-spectrum antibiotic (4.7±1.7 days in group 1, 3.9±1 days in group 2 with p = 0.160). The rate of de-escalation was higher in group 2 (30/62, 48.4%) than in group 1 (24/92, 26.1%) with p = 0.004. A reduction of 1.1 days of antibiotic treatment (group 1, 7.7±2.2 and group 2, 6.7±2.2, with p = 0.005) and 2 more antibiotic free-days free in PICU in group 2 were observed (p = 0.001), without adverse outcomes. CONCLUSIONS: Procalcitonin-guided protocol for stewardship after cardiac surgery seems to be safe and useful to decrease the antibiotic exposure. This protocol could help to reduce the duration of broad-spectrum antibiotics and the duration of antibiotics in total, without developing complications or adverse effects.

Extreme Hyperferritinemia in Dizygotic Twins With Human Parechovirus-3 Infection.

Human parechovirus-3 has been associated with severe clinical manifestations in infants, such as sepsis-like illness and meningoencephalitis. Nevertheless, the vast majority of patients have a favorable outcome. We report the occurrence of this infection in dizygotic infants with extreme hyperferritinemia and a transient impairment of natural killer cell cytotoxicity.

Performance of a rapid multi-analyte 2-photon excitation assay in children with acute respiratory infection.

The purpose of this study is to evaluate the diagnostic performance of the novel 2-photon excitation-based mariPOC© Assay (ArcDia Laboratories, Turku, Finland) for antigen detection of respiratory viruses versus real-time polymerase chain reaction (PCR). The mariPOC Assay and 2 multiplex real-time PCR techniques were performed on nasopharyngeal samples from pediatric patients with suspicion of acute respiratory infection admitted to a children's hospital in Spain during October 2011 to January 2013. A total of 233 samples were studied. Sensitivities and specificities (95% confidence interval) of the mariPOC Assay were for respiratory syncytial virus (RSV), 78.4% (69.7-85.6) and 99.2% (96.3-100.0); influenza virus (IFV) A, 66.7% (26.2-94.0) and 99.6% (97.9-100.0); IFV-B, 63.6% (33.6-87.2) and 100.0% (98.7-100.0); human metapneumovirus (hMPV), 60.0% (34.5-81.9) and 100.0% (98.6-100.0); adenovirus (ADV), 12.5% (0.6-48.0) and 100.0% (98.7-100.0), respectively. The mariPOC Assay is a highly specific method for simultaneous detection of 8 respiratory viruses but has sensitivities that range from moderately high for RSV to moderate for IFV and hMPV and low for ADV.

Cost of hospitalizing children with invasive pneumococcal pneumonia.

BACKGROUND: Although invasive pneumococcal pneumonia remains responsible for a significant number of child hospitalizations, specific data on hospital resource utilization and related costs are limited. OBJECTIVES: To assess the cost of hospitalizing children with invasive pneumococcal pneumonia and identify the cost determinants of the disease. PATIENTS AND METHODS: Economic evaluation based on an observational study of all children <18 years of age with culture-proved invasive pneumococcal pneumonia admitted to a referral hospital in Barcelona (Spain) during the period January 2001-December 2011. Analysis included demographic, microbiological, epidemiological and clinical variables. RESULTS: A total of 135 children were included in the study (median age 3.3 years). PCV13 serotypes were detected in 132 (97.8%) cases. Median hospital cost was €4533 (€4078-5435, 95% CI). Median length of stay was 11.0 days (10.6-13.0 days, 95% CI). Variables significantly associated with increased cost in the multivariate analysis were complicated pneumonia (≥2 and 1 complication) versus non-complicated pneumonia (€4919 and €2822 vs. €1399), performance of surgery versus no surgery (€4849 vs. €1435), intensive care versus no intensive care (€6488 vs. €3862) and identification of non-PCV7 serotypes versus PCV7 serotypes (€4656 vs. €1470). CONCLUSION: Invasive pneumococcal pneumonia in children makes substantial demands on hospital health care and financial resources that could be mitigated with universal PCV13 childhood immunization programmes and early management of complications.

Withholding or withdrawing life-sustaining treatments: an 8-yr retrospective review in a Spanish pediatric intensive care unit.

OBJECTIVE: To determine the death rate of patients who died in our pediatric intensive care unit after a decision to withhold or withdraw life-sustaining treatment was made and to describe the epidemiologic data, clinical (acute and chronic) conditions, end-of-life care, and decision-making processes corresponding to these patients. DESIGN: Long-term retrospective review of patients' charts. SETTING: Mixed university-affiliated pediatric intensive care unit. PATIENTS: Patients younger than 18 yrs old whose deaths occurred after life-sustaining treatment was withheld or withdrawn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Epidemiologic and clinical data, the treatments received, the decision-making process, and the end-of-life pathway were evaluated. Ninety-seven of 311 deaths occurred after a medical decision to withhold life-sustaining treatment. Among these patients, the most common reason for admission was respiratory failure (44 of 97), followed by cardiopulmonary arrest and sepsis. In 50 of 97 there was a previously known neurologic condition before admission, 11 of 97 had a neoplasm or hematologic malignancy, 10 of 97 had a congenital heart disease, and 8 of 97 had a neuromuscular disease. The most common action for forgoing life-sustaining treatment was withdrawal of treatment (chiefly respiratory support). The median time for deciding to withhold or withdraw life-sustaining treatment was on day 3 of admission. A total of 85 of 97 deaths occurred within 48 hrs after the decision was made and action taken. The decision to forgo life-sustaining treatment was proposed by the family in 14 of 97 patients, and there was an explicit agreement between the medical staff and the patient's family in 88 of 97. In all cases, palliative analgesic/sedative treatment effectively maintained the child's comfort. CONCLUSIONS: Withholding or withdrawing life-sustaining treatment was a frequent mode of death in our pediatric intensive care unit, occurring at a rate that falls in the midrange of literature values. The level of the parents' involvement with the team in the decision-making process, which was documented in 88 of 97 of the medical charts, was very high. Patients with chronic neurologic diseases or with severe cognitive sequelae constituted the main group in which the decision to forgo life-sustaining treatment was made.

Pandemic influenza A (2009 H1N1) in children with acute lymphoblastic leukaemia.

Pandemic influenza A (2009-H1N1) usually results in mild clinical illness, but in some individuals it can be life-threatening. There are no reports of this disease among paediatric patients with acute lymphoblastic leukaemia (ALL). We report ten consecutive patients with ALL and pandemic influenza treated in a single institution. Median age was 7 years (range: 3-12). All were treated with oseltamivir. There were no deaths. Two patients under intensive chemotherapy developed pneumonia and one required ventilatory support. ALL patients under maintenance treatment had mild disease. In conclusion, in our series only patients under intensive treatment developed a moderate to severe disease.