Objective To investigate the changing distribution and antibiotic resistance (AMR) profiles of Staphylococcus spp.and Enterococcus spp.isolated from children in China.Methods A retrospective analysis was conducted on the Staphylococcus spp.and Enterococcus spp.isolated from children under 18 years in 52 hospitals participating in the CHINET program from January 2015 to December 2021.The results of antimicrobial susceptibility test (AST) were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints (2021 edition).Results In the 7-year period,46334 strains of Staphylococcus were isolated from children,including 32537 strains of S.aureus and 13797 strains of coagulase-negative Staphylococcus.Meanwhile,16287 strains of Enterococcus were isolated,including E.faecium (8434 strains) and E.faecalis (6525 strains).S.aureus strains were mainly isolated from lower respiratory tract specimens (43.4％±6.7％),wound secretions (27.8％±4.3％) and blood (6.2％±1.2％).Most of the E.faecalis strains (58.6％±5.1％) and E.faecium strains (62.9％±2.0％) were isolated from urine.Both Staphylococcus and Enterococcus strains were most frequently isolated from internal medicine wards.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) was 29.5％ and 79.8％,respectively.The prevalence of MRSA was relatively high in neonates (0-28 days) and infants (>28 days to 1 year old),31.7％ and 30.9％,respectively.MRSA strains showed low and decreasing resistance rate to gentamicin,rifampicin,levofloxacin,and trimethoprim-sulfamethoxazole from 2015 to 2021.None of vancomycin-resistant or linezolid-resistant Staphylococcus was detected.Vancomycin-resistant or linezolid-resistant Enterococcus strains were rarely detected (0 to 1.0％).Moreover,more than 1.0％ of the E.faecalis isolates were resistant to linezolid in recent two years.Conclusions From 2015 to 2021,S.aureus,E.faecalis,and E.faecalis were still the most common gram-positive bacteria isolated from children.The prevalence of MRSA did not change significantly from 2015 to 2022.MRSA strains showed a trend of decreasing antimicrobial resistance.The antimicrobial resistance rates of E.faecalis and E.faecalis did not change significantly during the 7-year period.Ongoing AMR surveillance in the Staphylococcus and Enterococcus isolates from children is important for prevention,control,and treatment of the infections caused by Staphylococcus and Enterococcus in pediatric patients.

Objective To investigate the changing distribution and antibiotic resistance (AMR) profiles of Staphylococcus spp.and Enterococcus spp.isolated from children in China.Methods A retrospective analysis was conducted on the Staphylococcus spp.and Enterococcus spp.isolated from children under 18 years in 52 hospitals participating in the CHINET program from January 2015 to December 2021.The results of antimicrobial susceptibility test (AST) were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints (2021 edition).Results In the 7-year period,46334 strains of Staphylococcus were isolated from children,including 32537 strains of S.aureus and 13797 strains of coagulase-negative Staphylococcus.Meanwhile,16287 strains of Enterococcus were isolated,including E.faecium (8434 strains) and E.faecalis (6525 strains).S.aureus strains were mainly isolated from lower respiratory tract specimens (43.4％±6.7％),wound secretions (27.8％±4.3％) and blood (6.2％±1.2％).Most of the E.faecalis strains (58.6％±5.1％) and E.faecium strains (62.9％±2.0％) were isolated from urine.Both Staphylococcus and Enterococcus strains were most frequently isolated from internal medicine wards.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) was 29.5％ and 79.8％,respectively.The prevalence of MRSA was relatively high in neonates (0-28 days) and infants (>28 days to 1 year old),31.7％ and 30.9％,respectively.MRSA strains showed low and decreasing resistance rate to gentamicin,rifampicin,levofloxacin,and trimethoprim-sulfamethoxazole from 2015 to 2021.None of vancomycin-resistant or linezolid-resistant Staphylococcus was detected.Vancomycin-resistant or linezolid-resistant Enterococcus strains were rarely detected (0 to 1.0％).Moreover,more than 1.0％ of the E.faecalis isolates were resistant to linezolid in recent two years.Conclusions From 2015 to 2021,S.aureus,E.faecalis,and E.faecalis were still the most common gram-positive bacteria isolated from children.The prevalence of MRSA did not change significantly from 2015 to 2022.MRSA strains showed a trend of decreasing antimicrobial resistance.The antimicrobial resistance rates of E.faecalis and E.faecalis did not change significantly during the 7-year period.Ongoing AMR surveillance in the Staphylococcus and Enterococcus isolates from children is important for prevention,control,and treatment of the infections caused by Staphylococcus and Enterococcus in pediatric patients.

Objective:To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods:The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children′s hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children′s general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results:Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (β-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ 2=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ 2=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ 2=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10 9/L vs. (13±7)×10 9/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions:The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.

Objective To study the correlation between apolipoprotein E (APOE) genetic polymorphisms and sepsis in Chinese children.Methods The inpatients suffered with sepsis were enrolled as septic group and the healthy children from child health division were enrolled as control group.The study of APOE genotypes were carried out by polymerase chain reactions followed a high-resolution melting curve analysis.SPSS 16.0 statistical software was used for data analysis.Mann-Whitney U test was used to compare the age between the groups.Hardy-Weinberg equilibrium was tested using the Pearson x2-test.The x2-test was used to compare gender and the genotype distribution between the groups.The odd ratio (OR) was calculated together with its 95％ confidence interval (CI).Potential confounding effects of variables were corrected using a multivariate unconditional logistic regression model.All statistical tests were two-sided and P ＜ 0.05 indicates statistically significance.Results Among a total of 285 children collected from March 2011 to June 2012,there were 88 patients with sepsis and 197 healthy children.In the septic group,15 septic patients were complicated with central nervous system infection.Four apolipoprotein E genotypes were identified to be ε3/ε3,ε2/ε3,ε3/ε4,and ε2/ε4.The percentage of each genotype found in patients of the septic group and the control group was 64.4％ vs.73.1％ (ε3/ε3);16.8％ vs.10.7％ (ε2/ε3);18.8％ vs.14.7％ (ε3/ε4);0％ vs.1.5％ (ε2/ε4),respectively.The number of patients with the genotype ε3/ε3 among septic patients was significantly lower than that among the control individuals (P =0.047,1-β =0.334,OR =0.585,adjusted OR =0.559).The number of patients with the genotype ε3/ε3 among the septic patients with central nervous system infection was 33.3％,which was also significantly lower than that among the septic patients without CNS infection (67.1％).(P =0.014,1-β5 =0.685,OR =0.245,adjusted OR =0.275).Conclusions Apolipoprotein E genetic polymorphisms were associated with the occurrence of sepsis and central nervous system complications in children.The susceptibility of children with genotype ε3/ε3 to sepsis and central nerve system infection complications is significantly lower than that of children with other genotypes.

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.

Objective To assess the prevalence of Campylobacter in the children with acute bacterial diarrhea in Shanghai.Methods Epidemiological survey.Totally 6 641 children with acute bacterial infectious diarrhea from outpatients and inpatients in Children′s Hospital of Fudan University were submitted to the investigation during January 2011 to December 2012.The Campylobacter was isolated from stool samples collected from subjects in micro aerobic environment and identified by both multi-PCR and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry ( MALDI-TOF MS ) .Antimicrobial susceptibility tests were assayed by disk-diffusion method according to EUCAST standard.The isolates molecular typing was done by PFGE.SPSS16.0 was used to analyze the results.Results A total number of 6 641 subjects were enrolled, among them, 305 patients were infected with Campylobacter.The prevalence rate was 4.6%(305/6 641).Among the infected patients, 240 patients were infected with Campylobacter jejuni and 65 patients were infected with Campylobacter coli, the infectious rates of these two pathogenic bacteria were 3.6%and 1.0%, respectively.The peak infectious rate in patients older than 1 year of age was 6.2%(209/3 385) which was higher than that in children under 1 year of age (2.9%, 96/3 256),χ2 =35.98,P<0.001.The infectious rate in winter and spring (6.8%, 138/2 040) was higher than that in the other seasons ( 3.6%, 167/4 601 ) ,χ2 =28.59, P <0.001.Antimicrobial susceptibility test results showed that 91.5%( 279/305 ) isolates were resistant to ciprofloxacin and 11.8%( 36/305 ) isolates were resistant to erythromycin.A total of 9 genotypes of Campylobacter were found by PFGE cluster analysis.The similarity were ranged from 65.1%-100.0%for type A, 67.6%-100.0%for type B, 61.7%-100.0%for type C, 59.0%-100.0%for type D, 71.4%for type F, 80.0%for type H, 54.4%-90.9%for type I, and only one strain was classified as type E and G.Conclusions Campylobacter is a major pathogenic bacteria associated with acute bacterial infectious diarrhea in children especially in children older than 1 year of age in Shanghai.The prevalent pattern of this pathogen was sporadic and the sharp peak was in winter and spring.The isolates are highly resistant to ciprofloxacin but still sensitive to erythromycin.

Objective The aim of this study was to study the antibiotic resistance and resistance genes of methicillin-resistant Staphylococcus aureus (MRSA) in children from Shanghai area,and to determine the relationship between phenotypic and genotypic resistance profiles.Methods In this study,a total of 37 MRSA strains isolated from clinical specimens of hospitalized patients in Children's Hospital of Fudan University from March 2009 to November 2011 were collected.The mecA,ermA,ermB,ermC,aac (6') /aph (2),aph (3')-Ⅲ,ant (4',4),and qacA genes were detected by polymerase chain reaction (PCR).Resistance to antibiotics was detected by agar dilution tests.The data analysis was done by chi square test.Results Among the 37 MRSA isolates,all (100.0 ％) were mecA gene positive,9 (24.3％) were ermB gene positive,none was ermA/C gene positive,21 (56.8％) were aac (6')/aph (2) gene positive,10 (27.0％) were aph (3')-Ⅲ gene positive,6 (16.2％) were ant(4',4) gene positive,and 9 were qacA gene positive (24.3％).The positive rate of aac(6')/aph(2) in hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) was significantly higher than that of community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) (85.7％ vs18.8％,x2=60.340,P=0.000).Among the 37 MRSAisolates,37 (100.0％) were resistant to penicillin,ampicillin-sulbactam,cefazolin,cefoxitin and cefuroxime.The 37 isolates were all susceptible to teicoplanin,vancomycin,and linezolid.The resistant rates to gentamicin,erythromycin,clindamycin,sulfamethoxazole,fosfomycin,rifampicin,and levofloxacin were 51.4％ (19/37),81.1％ (30/37),51.4％ (19/37),16.2％ (6/37),27.0％ (10/37),37.8％ (14/37) and 54.0％ (20/37),respectively.Compared with CA-MRSA,HAMRSA isolates had significantly higher resistance rates to gentamicin (12.5％ vs 81.0％; x2 =17.033,P=0.000),levofloxacin (31.2％ vs 71.4％; x2 =5.903,P=0.017),and rifampin (6.2％ vs 61.9％; x2=11.959,P=0.001).The rate of gentamicin resistance in aac(6')/aph(2) gene carrying strains was significantly higher than strains not carrying the gene (x2 =29.757,P=0.000).Conclusions MRSA in children carry a variety of drug-resistant genes,showed multi-drug resistance.HA-MRSA carries more resistance genes,and has higher rates resistance to antimicrobials than CA-MRSA.

Objective To investigate the distribution and evolvement of resistance profiles of the pathogens isolated from children diagnosed with urinary tract infection (UTI).Methods The pediatric patients who were diagnosed with UTI in Children's Hospital of Fudan University from January 2001 to December 2010 were enrolled in this retrospective study.The clean catch midstream urine samples were collected and the pathogens were isolated by culture.Bacterial susceptibility test was performed by following a protocol of the standardized Kirby Bauer (KB) method.The enumeration data were analyzed by chi square test and the tendency of drug resistant rate was analyzed by curvilinear regression.Results A total of 10 686 pathogen strains were isolated during the past 10years.The major pathogen was Escherichia coli which counted for 38％ -56％ of the isolates.However,the proportion of Enterococcus faecalis (0 - 17％,F =34.075,P =0.000) and Enterococcus faecium (3 ％ - 15 ％,F =7.139,P =0.028) increased rapidly.The resistant rates of Escherichia coli to cefazolin,cefuroxime sodium,cefotaxime and ceftazidime were 35.8％- 62.3％(F=215.735,P=0.000),33.1％ -57.0％(F=70.674,P=0.000),19.0％ -56.5％(F=52.355,P=0.000) and 2.1％-23.5％(F=16.807,P=0.003),respectively.The resistant rate of Escherichia coli to ciprofloxacin was 23.4％ - 33.8 ％ (F=0.989,P=0.349),while the resistant rate of Escherichia coli to amikacin and cefoperozone/sulbactam were both less than 7％.There was no Escherichia coli isolate showing resistant to imipenem.The resistant rates of Enterococcus faecium to ampicillin and ciprofloxacin were higher than 60.0％ and 50.0％,respectively,while the resistant rate of Enterococcus faecalis to these two antibiotics decreased from 40.0％ to 9.6 ％ (F =17.497,P =0.009) and 60.0％ to 21.6％ (F=12.826,P=0.009),respectively.The resistant rate of Enterococcus faecium to nitrofurantoin decreased from 32 ％ (in the year of 2002) to 9.4％ (in the year of 2010,F=34.075,P=0.000) and the resistant rate of Enterococcus faecalis decreased from 9.2％ (in the year of 2005) to 1.4％ (in the year of 2010,F=7.139,P=0.028).The resistant rates to erythromycin were both higher than 75.0％ in both Enterococcus in recent 10 years.There was no Enterococcus isolates showing resistant to vancomycin.Conclusions Escherichia coli,Enterococcus faecalis and Enterococcus faecium are the most common pathogens associated with UTI in children.The proportions of Enterococcus faecalis and Enterococcus faecium among the pathogens of UTI are increasing.The antimicrobial activity of ampicillin to Enterococcus faecalis keeps at a high level.However,there are few drugs can be used for treating Enterococcus faecium infection.