1.Thoughts on the selection of antimicrobials for current pertussis treatment in China
Kaihu YAO ; Qinghong MENG ; Wei SHI ; Lin YUAN ; Yahong HU
Chinese Journal of Applied Clinical Pediatrics 2024;39(2):85-88
For a long time, macrolides have been the first choice for the antibacterial treatment for pertussis.However, in the past decade, resistance to macrolide antimicrobials has been common in clinically isolated Bordetella pertussis in China, which is in contradiction with the recommended macrolide treatment.Therefore, Trimethoprim-Sulfamethoxazole (TMP-SMZ) is suggested as the first choice for antibacterial treatment for pertussis in China, with a dosage determined according to age and body weight, lasting 14 days.If TMP-SMZ cannot be used, full-dose and full-course β-lactam antimicrobials may be used, of which the effects should be assessed carefully.The impact of other antibacterial drugs, such as quinolones and tetracyclines, on the elimination of Bordetella pertussis should also be evaluated as soon as possible to treat adult pertussis and potential cases caused by drug-resistant bacteria in future.
2.A comparative study on the clinical manifestations of children infected with erythromycin-resistant Bordetella pertussis of ptxP1 and ptxP3 genotypes
Mengyang GUO ; Bingsong WANG ; Lin YUAN ; Zhen LI ; Yahong HU ; Qianqian DU ; Wei SHI ; Yajuan WANG ; Kaihu YAO
Chinese Journal of Applied Clinical Pediatrics 2024;39(2):89-93
Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.
3.Focus on the epidemic cerebrospinal meningitis outbreaks and the global road map of defeating meningitis by 2030
Chinese Journal of Applied Clinical Pediatrics 2023;38(4):241-244
World Health Organization (WHO) reported that a total of 559 meningitis cases and 18 deaths were reported in the southeast of Niger from November 1, 2022 to January 27, 2023.Children were the major of patients.Among the laboratory confirmed cases, 93.7%(104/111) were epidemic cerebrospinal meningitis.Since 2021, the epidemic of meningococcal disease has attacked the gay and bisexual men in Florida, USA.This paper briefly reviews the occurrence and development of the two outbreaks of epidemic cerebrospinal meningitis, as well as the causes and countermeasures.The current prevention and control measures of meningitis is discussed based on the " Defeating meningitis by 2030: Global Road Map" issued by WHO in 2021.This paper is expected to attract the attention and to improve awareness and vigilance of domestic clinical and public health workers, which would lead to strengthen the surveillance, prevention and control of meningitis.
4.Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway
Fangjun WEN ; Lei GAO ; Yimin HU ; Kaihu SHI
China Pharmacy 2023;34(9):1053-1059
OBJECTIVE To investigate the effects of salidroside (Sal) on myocardial fibrosis and pyroptosis and its potential mechanism. METHODS The mice were randomly divided into control group, model group and Sal low-dose, medium-dose and high-dose groups, with 10 mice in each group. Except for the control group, the mice in other groups were injected subcutaneously with isoproterenol 5 mg/(kg·d)to prepare the myocardial fibrosis model. Since modeling, mice in the Sal low-dose, medium-dose and high-dose groups were given 10, 30 and 50 mg/kg of Sal by intragastric administration every day; control group and model group were given 10 mL/kg of normal saline by intragastric administration every day, for 14 consecutive days. After the last medication, the mice were sacrificed; hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell; Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction (CVF); quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ (Col Ⅰ), α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3), caspase-1 andgasdermin D (GSDMD) in myocardial tissues. The total protein expressions of Col Ⅰ, α-SMA, TLR4, NLRP3,caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry. RESULTS Compared with control group, the myocardial cells in the model group were enlarged, the arrangement of myocardial fibers was disordered, the matrix metabolism was significantly increased, the CVF in myocardial tissue was significantly increased, and the mRNA and protein expression levels of Col Ⅰ, α-SMA, TLR4, NLRP3, caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly (P<0.01). Compared with model group, the myocardial cell morphology was clearer, myocardial fibrosis was alleviated, and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees, especially in Sal high-dose group(P<0.05 or P<0.01). In addition, the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent. CONCLUSIONS Sal can significantly prevent the occurrence and development of myocardial fibrosis, and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.
5.In vitro antibacterial activity of pediatric Faropenem sodium against respiratory tract pathogens in children
Limin DONG ; Lin YUAN ; Wei GAO ; Qing WANG ; Wei SHI ; Yue LI ; Dan YU ; Qinghong MENG ; Gang LIU ; Kaihu YAO
Chinese Journal of Applied Clinical Pediatrics 2022;37(14):1086-1092
Objective:To evaluate the antibacterial activity of pediatric Faropenem sodium against common pathogens isolated from children′s respiratory tract in vitro, and to provide reference for its clinical research and application. Methods:Retrospective analysis.The minimum inhibitory concentration (MIC) of Faropenem sodium, Merope-nem, Imipenem and other antibiotics was determined by the agar dilution method.A total of 156 strains of Streptococcus pneumoniae [including 32 strains of Penicillin-susceptible Streptococcus pneumoniae (PSSP), 28 strains of Penicillin-intermediate Streptococcus pneumoniae (PISP) and 96 strains of Penicillin-resistant Streptococcus pneumoniae (PRSP)], 98 strains of Haemophilus influenza, 173 strains of Klebsiella pneumoniae, and 55 strains of Moraxella catarrhali clinical isolates were used.MIC 50, MIC 90 and the accumulative inhibition of the bacteria were investigated. Results:The MIC of Faropenem sodium against all the Streptococcus pneumoniae strains ranged from 0.010-2.000 mg/L.There was no difference in the MIC distribution of Faropenem sodium against PSSP, PISP and PRSP, and the MIC 90 value was all 1.000 mg/L.Faropenem sodium inhibited all the Haemophilus influenza strains at concentrations ranging from 0.030-8.000 mg/L.There was no difference in the MIC distribution of Faropenem sodium against Haemophilus influenza with or without β-lactamase and Ampicillin resistance.The MIC 90 value was all 4.000 mg/L.Ho-wever, the MIC of Faropenem sodium against Klebsiella pneumoniae ranged from 0.250 to above 32.000 mg/L, and both MIC 50 and MIC 90 were greater than 32.000 mg/L.Faropenem sodium inhibited all the Moraxella catarrhalis strains at concentrations ranging from 0.030-2.000 mg/L, with MIC 50 being 0.500 mg/L and MIC 90 being 1.000 mg/L. Conclusions:Antimicrobial susceptibility testing results in vitro demonstrate that pediatric Faropenem sodium has satisfactory antibacterial activities against Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis, but comparatively weak antibacterial activities against Klebsiella pneumoniae.
6.Single center clinical study on clinical characteristics and drug susceptibility of pneumococcal meningitis in children
Liang ZHU ; Xin GUO ; Xi WANG ; Zhenzhen DOU ; Kaihu YAO ; Wei SHI ; Gang LIU
Chinese Journal of Applied Clinical Pediatrics 2020;35(7):550-554
Objective:To explore the clinical characteristics, drug resistance and the serotype distribution of the isolates from peadiatric patients with pneumococcal meningitis (PM).Methods:Clinical data, follow-up outcomes, drug susceptibility of isolated strains and serotyping results of 72 children diagnosed as PM and hospitalized in Beijing Children′s Hospital, Capital Medical University, from January 2012 to December 2017 were retrospectively analyzed, and the independent risk factors of mortality in the PM patients were analyzed.Results:There were 46 males and 26 females.In 72 PM cases, with the age ranging from 1 month to 9 years, and hospital stay from 1 to 363 days(median, 22.0 d). A total of 71 cases (98.6%) had community-acquired infections.There were 28 cases (38.9%) with definite underlying diseases, the top 3 of which were cerebrospinal fluid rhinorrhea(6 cases), head trauma (4 cases)and immunodeficiency diseases (4 cases). Fever (72 cases, 100.0%) was the most common clinical symptom, followed by depression of spirit, change of consciousness (46 cases, 63.9%), vomitting (45 cases, 62.5%), convulsion (42 cases, 58.3%), increased tension of anterior fontanelle (27 cases, 37.5%) and headache (17 cases, 23.6%) .There were 44 cases (61.1%) of neurological complications, including 29 cases (40.3%) of subdural effusion.Bacterial meningitis recurred in 2 cases, both of which were recurrent Streptococcus pneumoniae infection.The intracranial infections were divided into meningitis (43.1%, 31/72 cases) and meningoencephalitis (56.9%, 41/72 cases) .The penicillin nonsensitive rate of meningitis isolates was 74.3%, and their resistance rate to Erythromycin, Clindamycin and Tetracycline were 95.7%, 95.7% and 89.1%, respectively.All meningitis isolates were susceptible to Levofloxacin, Vancomycin and Linezolid.The serotypes of 24 cases (33.3%) were identified, among which 8 strains were type 19F (33.4%), 5 strains were type 14, 4 strains were type 23F, 3 strains were type 6A, 2 strains were type 19A, 1 strain was type 1 and 1 strain was type 15B, with a 13-valent protein-polysaccharide conjugate vaccine (PCV13) coverage rate of 95.8%(23/24 strains). Among all children that were followed up, 51 cases got better, 21 cases (case fatality rate was 29.2%) were confirmed dead, and 21 children (29.2%) had sequelae.The multiva-riate Logistic regression analysis suggested that respiratory failure and peripheral blood white blood cell count <4×10 9/L were independent risk factors for death of children with PM(all P<0.05). Conclusions:Most PM cases in this center are children under 5 years old.Cerebrospinal fluid rhinorrhea, head trauma and immunodeficiency diseases are common underlying diseases in children with PM.Respiratory failure or peripheral blood leukopenia during the course of the disease may indicate a poor prognosis.
7.Evolution of antibiotic resistance of Streptococcus pneumoniae in children
Chinese Journal of Applied Clinical Pediatrics 2020;35(7):521-525
Streptococcus pneumoniae is the dominant pathogen of respiratory tract infections in children.Due to the long-term overuse of antibiotics, the growing resistance of Streptococcus pneumoniae against many kinds of antimicrobial agents, including the β-lactamides, the macrolides, the fluoroquinolones and so on, increasing infections caused by drug-resistant pneumococcal isolates, as well as the wide prevalence of such infections have posed great challenges to the selection of antibiotics in clinical practice.In this article, changes of resistance patterns of Streptococcus pneumoniae isolates against commonly used antimicrobial agents in Chinese children in the past 30 years were reviewed.The rapid development of antibiotic resistance of Streptococcus pneumoniae necessitates the prevention and control of Streptococcus pneumoniae infections as well as the reduction of unreasonable use of antibiotics.
8.Serotype distribution and antibiotic resistance pattern of 225 Streptococcus pneumoniae isolates from Urumqi Children′s Hospital in 2018
Juling TIAN ; Dandan LIU ; Xinghai SHI ; Wei GAO ; Lin YUAN ; Ju JIA ; Wenli ZHANG ; Kaihu YAO
Chinese Journal of Applied Clinical Pediatrics 2020;35(8):590-594
Objective:To investigate the serotype distribution and drug resistance of Streptococcus pneumoniae ( S. pneumoniae) isolated in Urumqi Children′s Hospital and to evaluate the significances of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing infection and controlling drug resistance. Methods:The S. pneumoniae isolates stored in clinical laboratory of Urumqi Children′s Hospital from January to December in 2018 were re-cultured.The serotypes were detected by capsule swelling experiment to assess the coverage rate of PCV13.The minimum inhibitory concentration (MIC) of Penicillin, Amoxicillin, Cefotaxime and Ceftriaxone were detected by E-test method, and the susceptibility of the isolates to Meropenem and other 9 antibiotics was detected by VITEC 2 Compact system. Results:A total of 225 S. pneumoniae strains were identified.The common serotypes were 19F (32.9%), 23F (12.0%), 19A (10.7%), 6B (10.2%) and 6A (8.0%). PCV13 coverage rate was 80.4%.There was no significant difference in serotype distribution and PCV13 coverage between children < 2 years old and ≥ 2 years old, as well as between Han and minority people.The 57.8% and 31.7% strains showed intermediate susceptibility and resistance against oral Penicillin, respectively.Based on the breakpoints for meningitis, 89.4% strains were resistant against pare-nteral Penicillin, and 47.5% and 64.6% strains were non-susceptible (mainly intermediately susceptible) to Ceftria-xone and Cefotaxime, respectively.The resistance rates of strains against Erythromycin, Sulfamethoxazole-trimethoprim and Tetracycline were as high as 98.1%, 67.6% and 89.6%, respectively.More than 90% tested isolates were susceptible to Amoxicillin, Meropenem, Levofloxacin or Moxifloxacin.PCV13 strains were more resistant to Penicillin than non-PCV13 strains. Conclusions:The serotypes 19F, 23F, 19A, 6B and 6A are common among the S. pneumoniae isolated in Urumqi.The coverage rate of PCV13 is about 80%.There was no significant difference in serotype distribution between Han and minority nationality children. S. pneumoniae were frequently resistant against Erythromycin.The high resistance to Penicillin and other beta-lactams should be taken into account when treatment is decided for suspected pneumococcal meningitis.Universal administration of PCV13 would be effective strategy to prevent pneumococcal infection in children and to control the drug resistance of S. pneumoniae.
9.Analysis of identification and antibiotic susceptibility of isolates identified as Streptococcus pneumoniae by routine methods with negative quellung reaction results
Ju JIA ; Fang DONG ; Lin YUAN ; Wei GAO ; Dandan LIU ; Wei SHI ; Kaihu YAO
Chinese Journal of Applied Clinical Pediatrics 2020;35(8):595-599
Objective:To determine whether these Streptococcus pneumoniae isolates identified by routine cli-nical methods that cannot be serotyped by the quellung reaction contain other species of viridans group streptococci and to determine the antibiotic susceptibility to provide reference for clinical medicine. Methods:A total of 105 isolates identified as Streptococcus pneumoniae by routine methods with negative quellung reaction results were enrolled in this study.Multilocus sequence analysis (MLSA) and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS) were used to identify species of these isolates.Broth microdilution method was used to detect susceptibilities of 14 antibiotics. Results:Twenty-four of the 105 isolates were identified as Streptococcus pseudopneumoniae by MLSA, and the remaining 81 were Streptococcus pneumoniae.Six isolates of Streptococcus pseudopneumoniae were misidentified as Streptococcus pneumoniae, and 3 isolates as Streptococcus mitis/ oralis by MALDI-TOF-MS; and 6 isolates of Streptococcus pneumoniae were misidentified as Streptococcus pseudopneumoniae.All isolates were susceptible to Vancomycin, Levofloxacin and Moxifloxacin.The non-susceptibility rates between Streptococcus Pneumoniae and Streptococcus pseudopneumoniae against Ceftriaxone(28.4% vs.58.4%), Chloramphenicol(39.5% vs.4.2%), Erythromycin(77.8% vs.95.8%) and Azithromycin(75.3% vs.95.8%) were obviously different. Conclusions:Routine clinical methods may misidentify some Streptococcus pseudopneumoniae as Streptococcus pneumoniae, and so does the MALDI-TOF-MS.In addition, Streptococcus pneumoniae isolates with negative results of the quellung reaction showed differences in antimicrobial resistance.And misidentification may affect the evaluation of pathogenic bacteria and antibiotic resistance.
10.Molecular and virulence characteristics of Staphylococcus aureus isolated from neonates
Wenjing GENG ; Shixiao DONG ; Fei JIN ; Wei SHI ; Kaihu YAO ; Mingyan HEI
Chinese Journal of Microbiology and Immunology 2020;40(6):429-436
Objective:To analyze the molecular and virulence characteristics of Staphylococcus aureus ( S. aureus) isolated from neonates. Methods:A total of 189 S. aureus isolates were collected from Beijing Children′s Hospital from January 2013 to October 2019 and analyzed by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCC mec) typing and Spa typing. Panton-valentine leucocidin (PVL)-encoding gene ( pvl) and 21 superantigen virulence genes were also detected. Results:The 189 S. aureus strains were isolated from respiratory secretions ( n=125), pus ( n=55), blood ( n=8) and pleural effusion ( n=1). There were 98 methicillin-susceptible S. aureus (MSSA) belonging to 42 MSSA clones and 91 methicillin-resistant S. aureus (MRSA) belonging to 26 MRSA clones. ST188-t189 and ST59-SCC mecⅣa-t437 were the predominant MSSA and MRSA clones accounting for 11% and 53%, respectively. The prevalence of pvl gene in MRSA isolates was significantly higher than that in MSSA isolates (32% vs 10%, P<0.01). There were 166 isolates (88%) carrying at least one superantigen virulence gene and among the 21 genes, seq and seb were the most common genes accounting for 47% and 43%, respectively. The most common superantigen genotype was seb- sek- seq. The positive rates of superantigen genes in MRSA and MSSA isolates were 85% (77/91) and 90% (88/98), respectively ( P>0.05). Conclusions:The main clones of MRSA and MSSA were different in neonates. ST59-SCC mecⅣa-t437 was the most predominant MRSA clone, while ST188-t189 was the most predominant MSSA clone. MSSA clones were more dispersed. The prevalence of pvl gene in MRSA was higher than that in MSSA. No significant difference in the prevalence of superantigen genes was observed between MRSA and MSSA.

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