A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study.

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34-7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82-1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6-8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6-8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).

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OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. DATA SOURCES: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". RESULTS: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. CONCLUSIONS: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

A Multicenter Epidemiological and Pathogenic Characteristics Study of Community-Acquired Bacterial Meningitis Children in China: Results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To explore the epidemiological and pathogenic characteristics of children with community-acquired bacterial meningitis. Methods: A multicenter, retrospective study was conducted among CABM patients under 15 years old from 33 hospitals in China from 2019 to 2020. The medical record, laboratory, and microbiological data were collected and analyzed. Results: A total of 1610 children with CABM were identified and presented at a median onset age of 45 days of whom 955 (59.3%) were males. CABM occurred mostly in infants <1 year of age (84.0%, 1352/1610). In etiology-confirmed cases, the pathogens were isolated from CSF culture in 515 (32.0%), 400 (24.8%) in blood culture, and 186 (11.6%) both in CSF and blood culture. In total, 126 pathogens were identified through CSF mNGS in 330 CABM cases; 21 S. pneumoniae isolates were detected in 83 CABM cases by antigen detection method. Major pathogens were E. coli (195, 24.7%), GBS (170, 21.5%), and S. pneumoniae (157, 19.9%). GBS (29.3%, 22/75) was the first pathogen of CABM in neonates aged 0-6 days old, while E. coli (44.7%, 76/170) in 7 to 28 days of age; S. pneumoniae (96.2%, 151/157) was the most common pathogen in >3 months old cases. About 9.7% (19/195) strains of E. coli produced ultra­broad­spectrum ß­lactamases. The common intracranial imaging complications were subdural effusion and (or) empyema in 349 (21.7%), hydrocephalus in 233 (14.5%), and cerebral abscess in 178 (11.1%). A total of 389 (24.2%) cases were completely cured and 1088 (67.6%) cases improved. Among 166 patients (10.3%) with adverse outcomes, 32 cases (2.0%) died, and 37 cases (2.3%) relapsed. Conclusion: The onset age of CABM in children is usually within 1 year of age, especially <3 months. The primary pathogens in infants less than 3 months old are E. coli and GBS, and the dominant pathogen in children older than 3 months old is S. pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. CABM should not be excluded even if CSF leukocyte counts are within normal range. Due to the low detection rate of pathogens in children with CABM, standardized CSF bacteriological examination should be paid more attention to increase the pathogen detection rate. Non­culture CSF detection methods may facilitate pathogenic diagnosis.

Predictive models for sepsis in children with Staphylococcus aureus bloodstream infections: a retrospective cohort study.

BACKGROUND: The presence of Staphylococcus aureus in the bloodstream can lead to the development of sepsis; however, the severity and risk factors of the systemic inflammatory response to Staphylococcus aureus bloodstream infections were unclear. This study is aimed to build a model to predict the risk of sepsis in children with Staphylococcus aureus bloodstream infections. METHODS: A retrospective analysis of hospitalized pediatric patients diagnosed with Staphylococcus aureus bloodstream infections was performed between January 2013 and December 2019. Each patient was assessed using the pediatric version of the Sequential Organ Failure Assessment score (pSOFA) within 24 h of blood culture collection. A nomogram based on logistic regression models was constructed to predict the risk factors for sepsis in children with Staphylococcus aureus bloodstream infections. It was validated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Of the 94 patients included in the study, 35 cases (37.2%) developed sepsis. The pSOFA scores ranged from 0 to 8, with 35 patients having a pSOFA score of ≥ 2. Six children (6.4%) died within 30 days, who were all from the sepsis group and had different pSOFA scores. The most common organs involved in sepsis in children with staphylococcal bloodstream infections were the neurologic system (68.6%), respiratory system (48.6%), and coagulation system (45.7%). Hospital-acquired infections (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-7.2), implanted catheters (aOR, 10.4; 95% CI, 3.8-28.4), procalcitonin level ≥ 1.7 ng/mL (aOR, 15.4; 95% CI, 2.7-87.1), and underlying diseases, especially gastrointestinal malformations (aOR, 14.0; 95% CI, 2.9-66.7) were associated with Staphylococcus aureus sepsis. However, methicillin-resistant Staphylococcus aureus infection was not a risk factor for sepsis. The nomogram had high predictive accuracy for the estimation of sepsis risk, with an AUC of 0.85. CONCLUSIONS: We developed a predictive model for sepsis in children with Staphylococcus aureus infection.

Association of Maternal Body Mass Index During Early Pregnancy With Offspring Lower Respiratory Infections: A Nationwide Cohort Study.

OBJECTIVE: To assess whether or to what extent maternal obesity during early pregnancy could increase the risk of offspring lower respiratory infections (LRI). STUDY DESIGN: This population-based cohort included 688,457 live singleton births born in Denmark between 2004 and 2016. The exposure was maternal body mass index (BMI) during early pregnancy, and the outcome was LRI in offspring. Cox regression models were used to estimate hazard ratios with their 95% confidence intervals (CI) for the association. We also performed subanalysis stratified by the LRI onset age, number of infection episodes before the age of 3, infection pathogens, infection sites, duration of hospital stay due to LRI and allergic constitution of children. RESULTS: A total of 64,725 LRIs in offspring were identified during follow-up. Maternal overweight (BMI 25.0-29.9 kg/m 2 ), moderate or severe obesity (BMI 30.0-39.9 kg/m 2 ) and very severe obesity (BMI ≥40 kg/m 2 ) were associated with a 7% (95% CI: 5%-9%), 16% (95% CI: 14%-19%) and 21% (95% CI: 13%-28%) increased risk of LRI in offspring, respectively. Higher maternal BMI was positively associated with earlier onset age, more episodes before the age of 3, and longer hospital stay of LRI in offspring. In addition, allergic constitution of offspring significantly enhanced the effect of maternal BMI on offspring LRI (44% increased risk, 95% CI: 5%-97% for very severe obesity). CONCLUSIONS: Maternal BMI during early pregnancy might be a risk factor for offspring LRI, especially in children with allergic constitution.

High-altitude resident pulmonary edema induced by SARS-CoV-2 infection in children - A case series.

From December 2022 to January 2023, seven children aged ≤14 years and residing in an area at 2999 m without altitude change in the past month developed severe cough, dyspnea, cyanosis, and severe pulmonary lesions within 2-3 days after SARS-CoV-2 infection. They were diagnosed to have high-altitude resident pulmonary edema. They completely recovered following 4-7 days of treatment with oxygen inhalation, vasodilation, diuretics, and glucocorticoids.

Neurological Disorders following COVID-19 Vaccination.

Nowadays, people all over the world have been receiving different types of coronavirus disease 2019 (COVID-19) vaccines. While their effectiveness has been well recognized, various post-vaccination disorders are not fully understood. In this review, we discuss neurological disorders related to vascular, immune, infectious, and functional factors following COVID-19 vaccination, and attempt to provide neuroscientists, psychiatrists, and vaccination staff with a reference for the diagnosis and treatment of these diseases. These disorders may present as a recurrence of previous neurological disorders or new-onset diseases. Their incidence rate, host and vaccine characteristics, clinical manifestations, treatment, and prognosis differ significantly. The pathogenesis of many of them remains unclear, and further studies are needed to provide more evidence. The incidence rate of severe neurological disorders is relatively low, most of which are reversible or treatable. Therefore, the benefits of vaccination outweigh the risk of COVID-19 infection, especially among fragile populations.

Early environmental exposure to oxytetracycline in Danio rerio may contribute to neurobehavioral abnormalities in adult zebrafish.

The common antibiotic oxytetracycline (OTC) is nowadays commonly found in natural aquatic environments. However, the underlying mechanisms of low-dose OTC exposure and its neurotoxic effects on aquatic animals remain unknown. In this study, we exposed zebrafish larvae to environmental concentrations of OTC in early life and performed neurobehavioral, 16S rRNA gene sequencing, and transcriptomic analyses. OTC exposure resulted in hyperactivity of larvae and a significant reduction in the number of neurons in the midbrain. The expression levels of 15 genes related to neural function changed. Additionally, the composition of 65 genera of the gut microbiota of larvae was altered, which may be one of the reasons for the abnormal neural development. We further studied the long-term outcomes among adult fish long after cessation of OTC exposure. OTC treatment caused adult fish to be depressive and impulsive, symbolizing bipolar disorder. Adult fish exposed to OTC had significantly fewer neurons and their gut bacteria composition did not recover 104 days after terminating OTC exposure. Finally, we analyzed the correlation between the gut microbiota of larvae, genes related to neural function, and metabolites of adult fish brain tissue. The results showed that the abundance of several members of the biome in larvae was related to the transcription levels of genes related to neural function, which were related to the metabolic levels in the adult brain. In conclusion, our study showed that early-life exposure to environmental concentrations of OTC can lead to persistent neurobehavioral abnormalities until adulthood through dysbiosis in the gut microbiota.

Multidimensional analysis using low-dose computed tomography to evaluate the severity of Mycoplasma pneumoniae pneumonia in children.

Background: It is unclear whether local pathological pulmonary changes truly reflect the severity of childhood Mycoplasma pneumoniae infection, which is characterized by rapid progress and potential mortality. This study multi-dimensionally analyzed low-dose computed tomography findings to assess the severity of Mycoplasma pneumoniae infection and predict its progress in such patients. Methods: In all, 752 children with Mycoplasma pneumoniae pneumonia (MPP) who underwent low-dose computed tomography examinations from February 2016 to July 2020 were retrospectively enrolled to conduct a cohort study. Clinical and radiological variables were analyzed using univariate analysis, and radiological variables were further analyzed using multivariable logistic regression in severe cases. Then, the correlation between the key computed tomography features and clinical symptoms, laboratory indicators, and medical costs were assessed using the chi-squared and Kruskal-Wallis H tests. Kaplan-Meier curves and Cox regression models were created to evaluate the correlations between the key computed tomography features, fever duration, and the length of hospital stay. Results: Of the 752 included patients, 16.2% (122/752) developed severe MPP. Atelectasis, pleural effusion, and lung consolidation occurred in 9.7% (73/752), 15.8% (119/752), and 90.3% (679/752) of patients, respectively. In addition to pleural effusion, the number of lobes of lung consolidation was the highest risk feature of severe MPP. Patients with consolidation in 2, 3, and 4 lobes had a 1.0-, 3.1-, and 7.5-fold increased risk of severe MPP, compared with patients with consolidation in fewer than 1 lobe. The duration of fever prior to admission had no effect on the proportions of the lobar consolidation (P=0.14) but did have significant effect on the incidence of pleural effusion (P=0.004). Levels of inflammatory markers and medical costs rose consistently with the increase in the number of lobar consolidations (P<0.001). After adjustments for pleural effusion, 1, 2, 3, and 4 lobes of consolidation remained positively associated with fever duration [1 lobe: hazard ratio (HR) =1.55, 95% CI: 1.10-2.18; 2 lobes: HR =1.65, 95% CI: 1.13-2.42l; 3 lobes: HR =1.82, 95% CI: 1.11-2.98; 4 lobes: HR =2.87, 95% CI: 1.25-6.61] compared to 0 lobes of consolidation. Compared to 0 lobes of consolidation, 1, 2, 3, and 4 lobes of consolidation were also positively correlated with the length of hospital stay (1 lobe: HR =2.24, 95% CI: 1.73-2.89; 2 lobes: HR =2.56, 95% CI: 1.91-3.43; 3 lobes: HR =2.87, 95% CI: 1.90-4.32; 4 lobes: HR =4.12, 95% CI: 2.01-8.46). Conclusions: Lobar consolidation is a stable and reliable computed tomography feature that can be used to assess the severity of MPP in children. Quantitative analysis of lobar consolidation can comprehensively and accurately predict the progression of Mycoplasma pneumoniae. Low-dose computed tomography is recommended for children with severe MPP with complicated courses.

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children.

Purpose: Heparin-binding protein (HBP) is a novel biomarker for inflammatory diseases. This study aimed to investigate the role of serum HBP in community-acquired pneumonia (CAP) in children and the association of HBP with the severity and prognosis. Patients and Methods: A total of 125 children with CAP admitted to the hospital were enrolled in this retrospective study. We analyzed the differences in clinical characteristics and examination findings between patients with different levels of HBP. The severe or complicated CAP was defined as having severe radiographic findings and/or systemic manifestations. Receiver operator characteristic (ROC) curves detected the performance of biomarkers in identifying patients with severe or complicated pneumonia. The multivariate logistic regression models assessed the association between HBP levels and the severity and prognosis. Finally, we constructed a predictive model based on HBP. Results: The rate of severe or complicated CAP for patients with upper-quartile HBP concentration (≥60 ng/mL) was 54.8%, significantly higher than that of patients with lower HBP concentration (26.6%). The level of HBP is substantially correlated with neutrophil counts, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A protein (r = 0.31, 0.26, 0.36, and 0.26, respectively). HBP achieved the highest level of discrimination for severe or complicated CAP among the biomarkers. Higher HBP concentration (≥60 ng/mL) was associated with a three-fold higher risk of severe or complicated CAP (adjusted odds ratio = 3.11, p < 0.05). A predictive model including four characteristics (HBP, lactate dehydrogenase, age and non-viral infection) for predicting severe or complicated CAP (with area under the ROC curve = 0.75) was built to create a nomogram. Conclusion: Substantially elevated serum HBP is significantly associated with severe or complicated CAP and poor prognosis in children. This finding warrants further investigation of the function of HBP in the pathogenesis of CAP.

Safety and clinical efficacy of linezolid in children: a systematic review and meta-analysis.

BACKGROUND: We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial infections. METHODS: A systematic literature search was conducted up to April 23, 2021, using linezolid and its synonyms as search terms. Two reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort studies. The extracted studies were included in a single-rate meta-analysis of adverse events and clinical outcomes using random-effects models. RESULTS: A total of 1082 articles were identified, and nine studies involving 758 children were included in the meta-analysis. The overall proportion of adverse events was 8.91% [95% confidence interval (CI) = 1.64%-36.52%], with diarrhea (2.24%), vomiting (2.05%), and rash (1.72%) being the most common. The incidences of thrombocytopenia and anemia were 0.68% and 0.16%, respectively. Some specific adverse events, including rash and gastrointestinal events, were more frequent in the oral administration subgroup. In terms of efficacy, the overall proportion of clinical improvement was 88.80% (95% CI = 81.31%-93.52%). Children with a history of specific bacteriological diagnosis or concomitant antibiotic therapy had a 1.13-fold higher clinical improvement than children without such histories. The proportion of microbial eradication was 92.68% (95% CI = 84.66%-96.68%). The proportion of all-cause mortality was 0.16% (95% CI = 0.00%-7.75%). CONCLUSIONS: Linezolid was well-tolerated in pediatric patients and was associated with a low frequency of adverse events, such as anemia, thrombocytopenia, and neutropenia. Moreover, linezolid was effective in children with diagnosed and suspected Gram-positive infections.

The role of flexible bronchoscopy in children with Mycoplasma pneumoniae pneumonia.

PURPOSE: To explore the effectiveness of flexible bronchoscopy in pediatric Mycoplasma pneumoniae pneumonia (MPP). METHODS: This retrospective cohort study included children with MPP admitted between 2016 and 2019 in Shanghai. Tracheobronchial manifestations, etiologic findings, therapeutic effect, and health-economic indicators were assessed in bronchoscopy (plus bronchoalveolar lavage (BAL)) and non-bronchoscopy group. We used propensity-score matching and multivariable logistic regression to investigate the effect of bronchoscopy and BAL on disease recovery. RESULTS: In 900 children with MPP, 24/278 (8.6%) of those who underwent bronchoscopy had sputum plugs. Coinfection rate was four-fold enhanced by BAL (19.6% vs. 4.5%, p < 0.01) in patients with severe MPP (SMPP) and nearly doubled (10.8% vs. 5.9%, p = 0.03) in those without SMPP, compared with no BAL. Total of 224 (24.9%) patients had multilobar consolidation; after BAL, a significantly shorter lesion-resolution duration was observed on imaging (OR: 0.2, 95% CI: 0.0-0.7). However, longer fever duration (OR: 2.8, 95% CI: 1.7-4.8), hospital stay (OR: 3.1, 95% CI: 1.9-5.1), and higher costs were found in the bronchoscopy group than in the non-bronchoscopy group. CONCLUSIONS: Through BAL, coinfection may explain one-fifth of causes for SMPP. Bronchoscopy with BAL may increase the detection rate of pathogen and resolve pulmonary lesions in patients with multilobar consolidation. IMPACT: Flexible bronchoscopy with bronchoalveolar lavage is of great assistance in the timely detection of coinfection, sputum plug and inflammatory polyps in children with Mycoplasma pneumoniae pneumonia (MPP), and improves the recovery of lung damage in MPP patients with multilobar consolidation. This study provides new insights into the indications of flexible bronchoscopy for the diagnosis and treatment of pediatric patients with MPP.

Development of a model for early differentiation of adenovirus pneumonia from Mycoplasma pneumoniae pneumonia.

Background: Adenovirus pneumonia (AVP) and Mycoplasma pneumoniae pneumonia (MPP) have similar clinical manifestations such as a high prevalence of lung consolidation, making the differential diagnosis difficult before the etiology is reported. This study aimed to compare AVP and MPP, and to build a predictive model to differentiate them early. Methods: We selected 198 cases of AVP and 876 cases of MPP. Clinical manifestations, computed tomography (CT) features, and biomarkers were compared. A logistic regression model was built to predict AVP. The area under the curve (AUC) of the receiver-operating characteristic was calculated to evaluate the discriminant ability of the prediction model. Results: Patients in the AVP group were mainly infants and toddlers, while the MPP group had more pre-school age children. The rate of hypoxemia and severe pneumonia was 3- and 11-times higher, respectively, in the AVP group than in the MPP group (5.6% vs. 1.8%, 27.8% vs. 2.5%, P<0.01). The proportion of patients with a Pediatric Logistic Organ Dysfunction-2 score ≥2 was 10 times higher in the AVP group than in the MPP group (17.4% vs. 1.7%, P<0.01). Bilateral pneumonia was present in 90.2% of the AVP group. Biomarkers, such as interleukin (IL)-2 receptor, IL-10 and lactic dehydrogenase (LDH), were considerably higher in the AVP group than in the MPP group (P<0.01). The predictive model included eight variables, namely: age, severe pneumonia, bilateral pneumonia, ground-glass attenuation, consolidation, atelectasis, C-reactive protein, and LDH. The AUC was 86.6%. Conclusions: Compared with MPP, AVP affects younger children, presents a more severe respiratory tract involvement, results in a larger range of lung lesions, and is associated with higher inflammatory biomarkers. Our predictive model includes a combination of clinical features, imaging findings, and biomarkers. It may help pediatricians in the early differentiation of AVP from MPP.

Association of long-term effects of low-level sulfamethoxazole with ovarian lipid and amino acid metabolism, sex hormone levels, and oocyte maturity in zebrafish.

Sulfamethoxazole (SMZ) is an important antibiotic used to prevent and treat infections in both clinical settings and animal husbandry. High levels of SMZ may exhibit endocrine toxicity. Environmental SMZ enters the human body via food and water; however, the toxicity of environmental doses of SMZ and its effects on reproductive health are unknown. In the present study, zebrafish were exposed to low concentrations of SMZ (1000 and 5000 ng/L) from 2 h post-fertilization to 120 d post-fertilization. Consequently, the proportion of mature oocytes in adult female zebrafish ovarian tissue increased by 98.2 %, indicating that SMZ promotes ovarian maturation. Metabolomics analysis revealed significant changes in ovarian lipid and amino acid levels after SMZ treatment. An enzyme-linked immunoassay used to detect sex hormones in the ovaries showed that SMZ exposure significantly increased the levels of estradiol, a follicle-stimulating hormone, and of luteinizing hormone. Furthermore, an association analysis showed that most of the differentially expressed metabolites in the ovary were strongly correlated with the levels of sex hormones secreted by the pituitary gland. Therefore, significantly increased transcript levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone detected in brain tissue suggested that SMZ may exhibit ovarian toxicity via the hypothalamus. In vitro experiments were performed to demonstrate that SMZ targets neurons in the hypothalamus. Exposure to SMZ significantly increased the GnRH content in GnRH neurons. Finally, molecular docking simulations indicated the potential interaction of SMZ with G protein-coupled receptor 54; this molecular binding can activate, synthesize, and release GnRH in neurons. In conclusion, long-term environmental exposure to SMZ may induce ovarian toxicity by affecting the hypothalamus-pituitary-gonad axis.

Early life environmental antibiotic exposure and preschool allergic diseases: A biomonitoring-based prospective study in eastern China.

Background: Globally, the prevalence of allergic diseases remains high, as does the level of environmental antibiotics. It has been found that clinical antibiotic application may increase preschool allergy risk. However, few biomonitoring studies have been conducted about the association between early life environmental trace dose antibiotic exposure and preschool allergy. Objective: To analyze the association between prenatal environmental antibiotic levels and allergic diseases using logistic regression models. Methods: A total of 743 pregnant women and their offspring from the Shanghai Allergy Birth Cohort completed five years follow-up, and 251 mother-infant pairs were finally included. Maternal urine samples were collected for 15 antibiotic quantitative measurements using liquid chromatography-tandem mass spectrometry. The high-antibiotic group was defined as having at least half of antibiotics exceeding the median concentration. Allergic diseases were assessed by clinicians through clinical history, standardized questionnaires, and annual physical examinations until the age of five. Skin-prick-test (SPT) was performed at 5 years old. Results: The incidence of allergic diseases was generally higher in the high-antibiotic than that in the low-antibiotic group. Compared to the low-comprehensive antibiotic group, children in the high-antibiotic group were weakly associated with allergic diseases but had a 6-fold increased risk of food allergens sensitivity (OR: 7.09, 95% CI: 1.59, 31.74). Association of above-median single prenatal antibiotic concentration exposure and allergic diseases was also observed (azithromycin and asthma, OR: 2.72, 95% CI: 1.15, 6.42; enrofloxacin and wheeze, OR: 2.22, 95% CI: 1.22, 4.05; trimethoprim and atopic dermatitis, OR: 2.00, 95% CI: 1.08, 3.71). Moreover, children with higher prenatal norfloxacin levels were more sensitive to food allergens (OR: 5.52, 95%CI: 1.54, 19.71). Conclusion: Early-life environmental antibiotic exposure may be correlated with an increased risk of asthma, wheeze, atopic dermatitis, and SPT positivity for food allergens in 5-year-old children.

Longitudinal analysis of exposure to a low concentration of oxytetracycline on the zebrafish gut microbiome.

Oxytetracycline, a widely produced and administered antibiotic, is uncontrollably released in low concentrations in various types of environments. However, the impact of exposure to such low concentrations of antibiotics on the host remains poorly understood. In this study, we exposed zebrafish to a low concentration (5,000 ng/L) of oxytetracycline for 1 month, collected samples longitudinally (Baseline, and Days 3, 6, 9, 12, 24, and 30), and elucidated the impact of exposure on microbial composition, antibiotic resistance genes, mobile genetic elements, and phospholipid metabolism pathway through comparison of the sequenced data with respective sequence databases. We identified Pseudomonas aeruginosa, a well-known pathogen, to be significantly positively associated with the duration of oxytetracycline exposure (Adjusted P = 5.829e-03). Several tetracycline resistance genes (e.g., tetE) not only showed significantly higher abundance in the exposed samples but were also positively associated with the duration of exposure (Adjusted P = 1.114e-02). Furthermore, in the exposed group, the relative abundance of genes involved in phospholipid metabolism had also decreased. Lastly, we characterized the impact of exposure on zebrafish intestinal structure and found that the goblet cell counts were decreased (~82%) after exposure. Overall, our results show that a low concentration of oxytetracycline can increase the abundance of pathogenic bacteria and lower the abundance of key metabolic pathways in the zebrafish gut microbiome that can render them prone to bacterial infections and health-associated complications.