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Invasive Salmonella infections result in a significant burden of disease including morbidity, mortality, and financial cost in many countries. Besides typhoid fever, the clinical impact of non-typhoid Salmonella infections is increasingly recognized with the improvement of laboratory detection capacity and techniques. A retrospective multicenter study was conducted to analyze the clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in hospitalized children in China during 2016-2018. A total of 130 children with invasive Salmonella infections were included with the median age of 12 months (range: 1-144 months). Seventy-nine percent of cases occurred between May and October. Pneumonia was the most common comorbidity in 33 (25.4%) patients. Meningitis and septic arthritis caused by nontyphoidal Salmonella (NTS) infections occurred in 12 (9.2%) patients and 5 (3.8%) patients. Patients 12 months (OR: 16.04) and with septic shock (OR: 23.4), vomit (OR: 13.33), convulsion (OR: 15.86), C-reactive protein (CRP) ≥ 40 g/L (OR: 5.56), and a higher level of procalcitonin (PCT) (OR: 1.05) on admission were statistically associated to an increased risk of developing meningitis. Compared to 114 patients with NTS infections, 16 patients with typhoid fever presented with higher levels of CRP and PCT (P 0.05). The rates of resistance to ampicillin, sulfamethoxazole/trimethoprim, ciprofloxacin, and ceftriaxone among Salmonella Typhi and NTS isolates were 50% vs 57.3%, 9.1% vs 24.8%, 0% vs 11.2%, and 0% vs 9.9%, respectively. NTS has been the major cause of invasive Salmonella infections in Chinese children and can result in severe diseases. Antimicrobial resistance among NTS was more common.

Neuroblastoma is a common malignant tumor in children, and patients often have a poor prognosis. Long noncoding RNAs (lncRNAs) are involved in the regulation of neuroblastoma progression. However, the regulatory effect of lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) on neuroblastoma is still not clear. The expression levels of DANCR, miR-338-3p and β-1, 4-galactosyltransferase III (B4GALT3) were determined by quantitative real-time PCR. 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, flow cytometry and transwell assays were used to evaluate the proliferation, apoptosis, migration and invasion abilities of neuroblastoma cells. Moreover, western blot analysis was performed to assess the levels of B4GALT3 and the proliferation, apoptosis and migration-related proteins. Besides, a dual-luciferase reporter assay was used to verify the interactions among DANCR, miR-338-3p and B4GALT3. Mice xenograft models were used to ascertain the effect of DANCR on neuroblastoma tumor growth in vivo. Our results revealed that DANCR was highly expressed in neuroblastoma tissues and cells, and its silencing impeded the progression of neuroblastoma cells. DANCR could interact with miR-338-3p. Knockdown of miR-338-3p recovered the inhibitory effect of DANCR knockdown on neuroblastoma progression. B4GALT3 was a target of miR-338-3p. B4GALT3 overexpression reversed the suppression effect of DANCR silencing on neuroblastoma progression. In-vivo experiments further confirmed that DANCR silencing inhibited neuroblastoma tumor growth. Our results indicated that DANCR promoted B4GALT3 expression to increase the proliferation, migration and invasion of neuroblastoma cells via sponging miR-338-3p, which provided a theoretical basis for the targeted therapy of neuroblastoma.

Objective To assess clinical characteristics, outcomes and antimicrobial resistance of invasive Klebsiella pneumoniae (KP) infections in Chinese pediatric patients in hospital and community settings. Methods This retrospective study was conducted in the nine tertiary hospitals during 2016–2018. The 324 pediatric inpatients who had KP isolated from blood and cerebrospinal fluid and had complete medical records reviewed were included. We analyzed the risk factors, outcomes and antimicrobial resistance pattern of KP-infected patients based on comparison between healthcare-associated KP infections (HAI) and community-acquired infections. Results Of the 324 enrolled patients, 275 (84.9%) were clinically defined as HAI, including 175 (63.6%) neonates and 100 (36.4%) aged >28 days. The overall prevalence of CRKP was 38.2% (43.4% in HAI verse 8.7% in CAI, P

Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions.Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children’s hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification.Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2% (n = 2,331) were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections (43.2%, n = 6,379). WHO Watch group antibiotics accounted for 70.4% of prescriptions (n = 12,915). The most prescribed antibiotic ATC classes were third-generation cephalosporins (41.9%, n = 7,679), followed by penicillins/β-lactamase inhibitors (16.1%, n = 2,962), macrolides (12.1%, n = 2,214) and carbapenems (7.7%, n = 1,331).Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented.

Objective: To assess clinical characteristics, outcomes and antimicrobial resistance of invasive Klebsiella pneumoniae (KP) infections in Chinese pediatric patients in hospital and community settings.Methods:This retrospective study was conducted in the nine tertiary hospitals during 2016-2018. The eligible pediatric inpatients who had KP isolated from blood and cerebrospinal fluid and had complete medical records reviewed were included. We compared the clinical characteristics, outcomes and antimicrobial resistance between community-acquired infections (CAI) and healthcare-associated infections (HAI), neonates and children old than 28 days, and carbapenem-resistant KP (CRKP) and carbapenem-sensitive KP (CSKP) infections.Result:In a total of enrolled 324 patients, 275 (84.9%) were clinically defined as HAI; 188 (58.0%) were neonates and 175 (93.5%) were attributable to HAI. The prevalence of CRKP was 35.8% (40.4% in HAI verse 10.2% in CAI, P Conclusions:Most of KP infections were healthcare-associated and the prevalence of invasive CRKP infections was high in pediatric patients in China. The continuous efforts of strengthening infection prevention control interventions are needed to reduce the health burden of severe KP infections in Chinese children.

Background: Bacterial meningitis (BM) remains a devastating disease in children, and it causes substantial neurological morbidity and mortality worldwide. However, there are few large-scale studies on the pathogens causing pediatric bacterial meningitis (PBM) and their antimicrobial resistance (AMR) patterns in China. The present multicenter survey summarized the features of the etiologies of BM in children and characterized their AMR patterns.Methods: Data from 1193 cerebrospinal fluid bacterial isolates from children with BM who were admitted to 13 children’s hospitals in China from 2016 to 2018 were analyzed retrospectively.Results: Of the 1142 patients with PBM, 65.9% (753) were less than 1 year old, and more than two-fifths (513, 44.9%) were younger than 3 months. The three leading pathogens causing PBM were Staphylococcus epidermidis (S. epidermidis) (16.5%), Escherichia coli (E. coli) (12.4%) and Streptococcus pneumoniae (S. pneumoniae) (10.6%). Infants under 3 months of age were at a relatively high risk of infection by E. coli (116/523; 22.2%), Enterococcus faecium (75/523; 14.3%), S. epidermidis (57/523; 10.9%), and Group B Streptococcus (55/523, 10.5%). However, Children more than 3 months of age were at a relatively high risk of infection by S. epidermidis (140/670; 20.9%), S. pneumoniae (117/670; 17.5%), and Staphylococcus hominis (57/670; 8.5%). Greater than 93.0% of E. coli isolates were sensitive to cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam, amikacin and carbapenems, and the resistance rates to ceftriaxone, cefotaxime and ceftazidime were 49.4%, 49.2% and 26.4%, respectively. From 2016 to 2018, the proportion of methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) isolates declined from 80.5% to 72.3%, and the frequency of penicillin-resistant Streptococcus pneumoniae (PRSP) isolates increased from 75.0% to 87.5%. The proportion of extended-spectrum β-lactamase (ESBL)-producing E. coli fluctuated between 44.4% and 49.2%, and the detection rate of ESBL production in Klebsiella pneumoniae (K. pneumoniae) ranged from 55.6% to 88.9%. The resistance of E. coli strains to carbapenems was 5.0%, but the overall prevalence of carbapenem-resistant (CR) K. pneumoniae was high (54.5%).Conclusions: The resistance of CoNS to methicillin and the high incidence of ESBL production in Gram-negative Enterobacteriaceae pose a critical challenge to infection control. Carbapenem-resistant K. pneumoniae isolates are a serious issue for the treatment of children with PBM.

This study aimed to investigate the microbiological profiles and antimicrobial resistance patterns of bloodstream pathogens in Chinese children. This retrospective study was conducted at 13 tertiary hospitals in China during 2016–2018. The first bloodstream isolates of the same species from one pediatric patient < 18 years were included to this study for analysis. Antimicrobial susceptibility testing was determined based on minimum inhibitory concentrations or Kirby-Bauer disk diffusion methods according to the 2018 Clinical and Laboratory Standards Institute guidelines. Overall, 9345 nonduplicate bloodstream isolates were collected. Top 10 pathogens included Coagulase-negative staphylococcus (CoNS) (44.4%), Escherichia coli (10.2%), Klebsiella pneumoniae (5.9%), Staphylococcus aureus (5.0%), Streptococcus pneumoniae (4.9%), Pseudomonas aeruginosa(2.8%), Enterococcus faecium (2.7%), Stenotrophomonas maltophilia (2.4%), Salmonella spp. (2.3%), and Streptococcus agalactiae (2.0%). The commonest pathogens apart from CoNS in age group 0–28 days, 29 days–2 months, 3-11 months, 1–5 years, and ≥ 5 years were Escherichia coli (17.2%), Escherichia coli (14.0%), Escherichia coli (7.9%), Streptococcus pneumoniae (10.7%) ,and Staphylococcus aureus (13.6%), respectively. The overall prevalence of extended-spectrum β-lactamases-producing Enterobacteriaceae, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, and carbapenem-resistant Pseudomonas aeruginosa were 41.4, 28.4, 31.7, and 5.6%, respectively. The overall prevalence of methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus was 38.1, 28.3, and 0.7%, respectively. The major bacterial pathogens have differences in different age groups, ward types, and regions in Chinese children, and the commonest causing microorganism was the Escherichia coli, especially in neonates and infants. High prevalence of important resistant phenotypes is of a serious concern.

BackgroundSevere acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus which mainly spreads from person-to-person. Presence of SARS-CoV-2 has been constantly reported in stools of patients with coronavirus disease 2019 (COVID-19). However, there is a paucity of data concerning fecal shedding of the virus in pediatric patients.ObjectiveTo investigate dynamic changes of SARS-CoV-2 in respiratory and fecal specimens in children with COVID-19.MethodsFrom January 17, 2020 to February 23, 2020, three pediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data of these children were collected. Real-time fluorescence reverse-transcriptase-polymerase-chain reaction (RT-PCR) was performed to detect SARS-CoV-2 RNA in throat swabs and fecal specimens. Patients were followed up to March 10, 2020, the final date of follow-up, and dynamic profiles of RT-PCR results were closely monitored.ResultsAll the three pediatric cases were household contacts of adults whose symptoms developed earlier. Severity of disease was mild to moderate and fever was the most consistent and predominant symptom at onset of illness of these children (two cases had body temperature higher than 38.5°C). All children showed increased lymphocytes (>4.4×109 /L) with normal white blood cell counts on admission. Radiological changes were not typical for COVID-19. All children showed good response to supportive treatment. Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained positive in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 turned negative 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.InterpretationSARS-CoV-2 may exist in gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

Background: With the ongoing outbreak of Coronavirus Disease 2019 (COVID-19), infected patients within and beyond the epidemic area, Wuhan, China, showed different epidemiological and clinical characteristics. Little is known about the pattern of coinfection with other common respiratory pathogens in COVID-19 patients outside of Wuhan. Methods: We conducted a double-centre study recruiting 68 patients with severe acute respiratory coronavirus 2 (SARS-CoV-2) infection confirmed by nucleic acid testing in Qingdao and Wuhan from January 17 to February 16, 2020. Indirect immuno-fluorescence was performed to detect the specific IgM antibody against common respiratory pathogens in collected acute phase serum. Findings: Of the 68 patients with SARS-CoV-2 infection, 30 (44.12%) were from Qingdao. The median age of Qingdao and Wuhan patients were 50 (IQR: 37-59) and 31 (IQR: 28-38) years, respectively, and the majority of patients were female in Qingdao (60.00%) and Wuhan (55.26%). Among COVID-19 patients in Qingdao, 24 (80.00%) of them had IgM antibodies against at least one respiratory pathogen, whereas only one (2.60%) of the patients in Wuhan had positive results for serum IgM antibody detection ( P

Objectives To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas. Study design Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification. Results A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%). Conclusions Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics.