Metagenomic Next-Generation Sequencing of Bloodstream Microbial Cell-Free Nucleic Acid in Children With Suspected Sepsis in Pediatric Intensive Care Unit.
Ontology highlight
ABSTRACT:
SUBMITTER: Yan G
PROVIDER: S-EPMC8421769 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundSevere pneumonia due to lower respiratory tract infections (LRTIs) is a significant cause of morbidity and mortality in children. Noninfectious respiratory syndromes resembling LRTIs can complicate the diagnosis and may also make targeted therapy difficult because of the difficulty of identifying LRTI pathogens. In the present study, a highly sensitive metagenomic next-generation sequencing (mNGS) approach was used to characterize the microbiome of bronchoalveolar lavage fluid (BALF) in children with severe lower pneumonia and identify pathogenic microorganisms that may cause severe pneumonia. The purpose of this study was to use mNGS to explore the potential microbiomes of children with severe pneumonia in a PICU.MethodsWe enrolled patients meeting diagnostic criteria for severe pneumonia admitted at PICU of the Children's Hospital of Fudan University, China, from February 2018 to February 2020. In total, 126 BALF samples were collected, and mNGS was performed at the DNA and/or RNA level. The pathogenic microorganisms in BALF were identified and correlated with serological inflammatory indicators, lymphocyte subtypes, and clinical symptoms.ResultsmNGS of BALF identified potentially pathogenic bacteria in children with severe pneumonia in the PICU. An increased BALF bacterial diversity index was positively correlated with serum inflammatory indicators and lymphocyte subtypes. Children with severe pneumonia in the PICU had the potential for coinfection with viruses including Epstein-Barr virus, Cytomegalovirus, and Human betaherpesvirus 6B, the abundance of which was positively correlated with immunodeficiency and pneumonia severity, suggesting that the virus may be reactivated in children in the PICU. There was also the potential for coinfection with fungal pathogens including Pneumocystis jirovecii and Aspergillus fumigatus in children with severe pneumonia in the PICU, and an increase in potentially pathogenic eukaryotic diversity in BALF was positively associated with the occurrence of death and sepsis.ConclusionsmNGS can be used for clinical microbiological testing of BALF samples from children in the PICU. Bacterial combined with viral or fungal infections may be present in the BALF of patients with severe pneumonia in the PICU. Viral or fungal infections are associated with greater disease severity and death.
| S-EPMC10064343 | biostudies-literature
Project description:Background: Survivors of pediatric sepsis often develop new morbidities and deterioration in quality of life after sepsis, leading to a need for improved follow-up for children who survive sepsis. Objective: To implement a follow-up system for pediatric sepsis survivors in a pediatric health system. Methods: We performed a retrospective case series of patients treated for sepsis from October 2018 through October 2019 in a pediatric intensive care unit in a quaternary children's hospital, and describe implementation of a follow-up system for sepsis survivors. Program planning started in 2017 with multidisciplinary meetings including physical, occupational, and speech therapists, teachers, neuropsychologists, and coordinators from other survivorship programs (neonatology, stroke, and oncology). In 2018, a workshop was held to consult with local and national experts. The Pediatric Sepsis Survivorship Program launched in October 2018 led by a nurse coordinator who met with families to educate about sepsis and offer post-discharge follow-up. Patients with high pre-existing medical complexity or established subspecialty care were referred for follow-up through existing care coordination or subspecialty services plus guidance to monitor for post-sepsis morbidity. For patients with low-moderate medical complexity, the nurse coordinator administered a telephone-based health-assessment 2-3 months after discharge to screen for new physical or psychosocial morbidity. Patients flagged with concerns were referred to their primary physician and/or to expedited neuropsychological evaluation to utilize existing medical services. Results: Of 80 sepsis patients, 10 died, 20 were referred to care coordination by the program, and 13 had subspecialty follow-up. Five patients were followed in different health systems, four were adults not appropriate for existing follow-up programs, four remained hospitalized, and four were missed due to short stay or unavailable caregivers. The remaining 20 patients were scheduled for follow-up with the Pediatric Sepsis Program. Nine patients completed the telephone assessment. Four patients were receiving new physical or occupational therapy, and one patient was referred for neuropsychology evaluation due to new difficulties with attention, behavior, and completion of school tasks. Conclusions: Implementation of an efficient, low-cost pediatric sepsis survivorship program was successful by utilizing existing systems of care, when available, and filling a follow-up gap in screening for select patients.
| S-EPMC8212949 | biostudies-literature
Project description:BackgroundPediatric sepsis remains a significant cause of morbidity and mortality worldwide. This study aimed to identify the incidence of sepsis and septic shock among patients admitted to the pediatric intensive care unit (PICU) of a tertiary center in Saudi Arabia. Patients' demographics and risk factors associated with sepsis-related mortality were also investigated.MethodsA retrospective cohort study was conducted in the PICU of King Abdulaziz Medical City, Jeddah (KAMC-J). KAMC-J is a tertiary care hospital in the western region of Saudi Arabia. A total of 2389 patients admitted to the PICU of KAMC-J between January 1, 2013 and December 31, 2017 were screened and evaluated for sepsis using The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).ResultsOf the 2389 total admissions to the PICU, 113 patients (4.9%) met the definition of Sepsis-3; 50.4% of the 113 patients met the definition of septic shock. Most patients (66.3%) were less than 6 years old, and 52.2% were male. Eight-five patients (75.2%) had underlying comorbidities. The respiratory system was the most common primary site of infection (57.5%). Bacterial and viral infections were the most common infectious etiology with reported rates of 29.2 and 21.2%, respectively. The median duration of PICU stay was 8 days and the 28-day PICU mortality rate was 23.9%. A Pediatric Sequential Organ Failure Assessment (pSOFA) Score greater than four and a pre-existing percutaneous central venous catheter were associated with a significant increase in mortality, with adjusted odds ratios of 3.6 (95% confidence interval: 1.30-9.93) and 9.27 (95% confidence interval: 1.28-67.29), respectively.ConclusionsThe incidence of sepsis in our institution is comparable to that reported internationally; however, the mortality rate is higher than that of developed countries. Nationwide studies identifying sepsis epidemiology are needed to improve the outcome of pediatric sepsis. Following international guidelines for central-line insertion and maintenance is of paramount importance.
| S-EPMC8103596 | biostudies-literature
Project description:Early diagnosis and triage of sepsis improves outcomes. We aimed to identify biomarkers that may advance diagnosis and triage of pediatric sepsis. Serum and plasma samples were collected from young children (1-23 months old) with sepsis on presentation to the Pediatric Intensive Care Unit (PICU-sepsis, n?=?46) or Pediatric Emergency Department (PED-sepsis, n?=?58) and PED-non-sepsis patients (n?=?19). Multivariate analysis was applied to distinguish between patient groups. Results were compared to our results for older children (2-17 years old). Common metabolites and protein-mediators were validated as potential biomarkers for a sepsis-triage model to differentiate PICU-sepsis from PED-sepsis in children age 1 month-17 years. Metabolomics in young children clearly separated the PICU-sepsis and PED-sepsis cohorts: sensitivity 0.71, specificity 0.93, and AUROC?=?0.90?±?0.03. Adding protein-mediators to the model did not improve performance. The seven metabolites common to the young and older children were used to create the sepsis-triage model. Validation of the sepsis-triage model resulted in sensitivity: 0.83?±?0.02, specificity: 0.88?±?0.05 and AUROC 0.93?±?0.02. The metabolic-based biomarkers predicted which sepsis patients required care in a PICU versus those that could be safely cared for outside of a PICU. This has potential to inform appropriate triage of pediatric sepsis, particularly in EDs with less experience evaluating children.
| S-EPMC6226431 | biostudies-literature
Project description:Background: The gut is thought to play an important role in the pathogenesis of sepsis. Changes in the gut microbiota are closely related to the occurrence and development of human diseases, but few studies have focused on taxonomic composition of gut microbiota in septic patients. Knowledge of changes in the gut microbiota is a key issue in intensive care. Clinicians must understand how an altered gut microbiota affects the susceptibility and prognosis of septic patients. Measurements and Main Results: In the single-center case control study, 20 septic patients and 20 healthy children were recruited. The taxonomic composition of gut microbiota was determined via 16S rRNA gene sequencing. Gut microbiota diversity in children with sepsis was significantly reduced compared with that in healthy children. The taxonomic composition of gut microbiota can effectively distinguish children with sepsis from healthy children. Thirteen taxa of gut microbiota were significantly increased in the guts of children with sepsis compared with those of healthy children. The increased abundances of Enterococcaceae, Enterococcus, and Enterococcus durans in gut of septic patients were significantly positively correlated with blood inflammation indicators CRP and WBC. The abundances of seven bacteria were significantly decreased in the guts of septic children compared with those of healthy children. The decreased abundance of Bifidobacteriales in gut of septic patients is significantly negatively correlated with blood inflammation index WBC. A machine-learning classifier was built for distinguishing sepsis and achieved the AUC value of 81.25%. It shows that the composition of gut microbiota has certain potential for diagnosis of sepsis. Conclusions: Gut microbiota alterations in septic patients exhibit proliferation of opportunistic pathogenic bacteria, the massive reduction of the commensal flora, and the significant decrease in the diversity of the gut microbiota. Dysbiosis may also account for some changes in the inflammation indexes.
| S-EPMC8058355 | biostudies-literature
Project description:Among surgical intensive care unit (SICU) patients, it is difficult to distinguish bacterial sepsis from other causes of systemic inflammatory response syndrome (SIRS). Biomarkers have proven useful to identify the presence of bacterial infection. We enrolled a prospective cohort of 69 SICU patients with suspected sepsis and assayed the concentrations of 9 biomarkers (?-2 macroglobulin [A2M], C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) at baseline, 24, 48, and 72hours. Forty-two patients (61%) had bacterial sepsis by chart review. A2M concentrations were significantly lower, and PCT concentrations were significantly higher in subjects with bacterial sepsis at 3 of 4 time points. Using optimal cutoff values, the combination of baseline A2M and 72-hour PCT achieved a negative predictive value of 75% (95% confidence interval, 54-96%). The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis.
| S-EPMC4841711 | biostudies-literature
Project description:Background Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples. Methods A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients’ lung BALF microbiomes were explored using the mNGS data. Results Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%). Conclusions mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.
| S-EPMC10466250 | biostudies-literature
Project description:BackgroundInfected pancreatic necrosis (IPN) is a life-threatening complication of acute pancreatitis (AP). Timely diagnosis of IPN could facilitate appropriate treatment, but there is a lack of reliable non-invasive screening tests. In this study, we aimed to evaluate the diagnostic value of plasma metagenomic next-generation sequencing (mNGS) based on circulating microbial cell-free DNA in patients with suspected IPN.MethodsFrom October 2020 to October 2021, 44 suspected IPN patients who underwent plasma mNGS were reviewed. Confirmatory diagnosis of IPN within two weeks after the index blood sampling was considered the reference standard. The confirmation of IPN relied on the microbiological results of drains obtained from the necrotic collections. The distribution of the pathogens identified by plasma mNGS was analyzed. Positive percent agreement (PPA) and negative percent agreement (NPA) were evaluated based on the conformity between the overall mNGS results and culture results of IPN drains. In addition, the clinical outcomes were compared between mNGS positive and negative patients.ResultsAcross all the study samples, thirteen species of bacteria and five species of fungi were detected by mNGS. The positivity rate of plasma mNGS was 54.55% (24/44). Of the 24 mNGS positive cases, twenty (83.33%, 95% CI, 68.42-98.24%) were consistent with the culture results of IPN drains. The PPA and NPA of plasma mNGS for IPN were 80.0% (20/25; 95% CI, 64.32-95.68%) and 89.47% (17/19; 95% CI, 75.67-100%), respectively. Compared with the mNGS negative group, patients in the positive group had more new-onset septic shock [12 (50.0%) vs. 4 (20.0%), p = 0.039].ConclusionIPN relevant pathogens can be identified by plasma mNGS, potentially facilitating appropriate treatment. The clinical application of mNGS in this cohort appears feasible.
| S-EPMC9356476 | biostudies-literature
Project description:IntroductionConsistent medical knowledge acquisition while caring for the critically ill can be challenging for learners and educators in the pediatric intensive care unit (PICU), a unit often distinguished by fluctuating acuity and severity. We implemented a standardized didactic curriculum for PICU residents to facilitate their acquisition and retention of knowledge in core PICU topics.MethodsWe developed a comprehensive standardized curriculum for PGY 2-PGY 4 PICU pediatric and internal medicine-pediatric residents. Thirteen core topics were administered as 30-minute didactic sessions during the rotation, using either PowerPoint slides or a dry-erase board. Residents were tested to assess knowledge acquisition and retention.ResultsSeventy-eight residents participated, 86% of whom completed posttests. Seventeen percent completed follow-up tests. Of the learners who participated, 60 (77%) completed pretests and posttests, indicating their confidence level each time. The pretest mean was 55% (SD = 14.4%), and the posttest mean was 64% (SD = 15.6%). This 9% increase was statistically significant (p = .001; CI, 3.9% to 14.8%). The follow-up test at 3 months, completed by 15% of this subgroup, demonstrated a mean score of 62% (SD = 14.5%). When matched with posttest scores (mean score of 64%, SD = 13.3%), there was no significant difference (p = .7398; CI, -11.7% to 16.2%), suggesting retention of previously acquired knowledge.DiscussionOur standardized didactic curriculum effectively facilitated the acquisition and retention of the medical knowledge of core PICU topics among PICU residents, in addition to their usual experiential learning.
| S-EPMC7566227 | biostudies-literature