1.Study on antibiotic resistance and resistance genes of methicillin-resistant Staphylococcus aureus in children
Xia WU ; Chuanqing WANG ; Xiufeng YAN ; Aimin WANG ; Leiyan HE ; Zuhuang MI ; Hui YU
Chinese Journal of Infectious Diseases 2013;31(11):641-645
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.
2.The correlation between the apolipoprotein E genetic polymorphisms and sepsis in children
Meixiu LIU ; Changsheng YANG ; Qiang LI ; Leiyan HE ; Pan FU ; Aimin WANG ; Chuanqing WANG
Chinese Journal of Emergency Medicine 2017;26(6):622-626
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.
3.Epidemiological survey of Campylobacter infection associated with acute bacterial infectious children diarrhea in Shanghai
Leiyan HE ; Chuanqing WANG ; Aimin WANG ; Jianchang XUE ; Jianming SONG ; Pan FU ; Xuebin XU
Chinese Journal of Laboratory Medicine 2014;(10):743-747
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.
4.Distribution and evolvement of resistance profiles of the pathogens in children diagnosed with urinary tract infection in Children's Hospital of Fudan University in the recent 10 years
Lijun YIN ; Aimin WANG ; Jianchang XUE ; Jianming SONG ; Leiyan HE ; Chuanqing WANG
Chinese Journal of Infectious Diseases 2011;29(12):735-739
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.
5.Progress in the biomarker discovery for drug-induced liver injury.
Leiyan HE ; Yaoxue GUO ; Chun LI ; Ye DENG ; Qizhi ZHANG ; Wenxing PENG
Acta Pharmaceutica Sinica 2015;50(8):959-65
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.