Research progress on the mechanism of -lactam resistance in group A Streptococci in vivo / 中国当代儿科杂志

-lactams, including penicillin, have been used for over 80 years in the treatment of group A Streptococcus (GAS) infections. Although -lactam-resistant GAS strains have not been identified in vitro tests, clinical treatment failures have been reported since the 1950s. The mechanism underlying the clinical failure of -lactam treatment in GAS infections remains unclear. Previous research has suggested that -lactam resistance in GAS in vivo is associated with reduced drug susceptibility of strains, bacterial inoculation effects, biofilm formation, the effect of coexisting bacteria, bacterial persistence, and bacterial internalization into host cells. This article reviews the main reports on -lactam treatment failure in GAS infections and analyzes the possible mechanisms of -lactam resistance in vivo. The findings aim to contribute to future research and clinical approaches in the field.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Recent research on the epidemiology and preventive strategies of neonatal group B Streptococcus infection in the latest decade / 中国当代儿科杂志

Currently, the main strategy for preventing neonatal group B Streptococcus (GBS) infection is prenatal screening combined with intrapartum antibiotic prophylaxis, which has effectively reduced the incidence of neonatal GBS early-onset disease. However, the burden of GBS infection is still significant. The intrapartum antibiotic prophylaxis strategy has limitations such as inducing antibiotic resistance and inability to effectively prevent GBS late-onset disease. It is crucial to develop and evaluate other prevention strategies, while paying close attention to assessing penicillin allergy in pregnant women and how to prevent GBS infection in neonates with negative maternal GBS screening. In recent years, there has been some progress in GBS vaccines and related immunological research, and the use of specific vaccines is expected to significantly reduce GBS infection in neonates.

Paying attention to the epidemic of group A Streptococcus infections in multiple European and American countries / 中国当代儿科杂志

At the end of 2022, the World Health Organization reported an increase in group A Streptococcus (GAS) infections, such as scarlet fever, in multiple countries. The outbreak primarily affected children under 10 years old, and the number of deaths was higher than anticipated, causing international concern. This paper reviews the current state of the GAS disease outbreak, its causes, and response measures. The authors aim to draw attention from clinical workers in China and increase their awareness and vigilance regarding this epidemic. Healthcare workers should be aware of the potential epidemiological changes in infectious diseases that may arise after the optimization of control measures for coronavirus disease 2019 to ensure children's health.

Clinical and molecular characteristics of Streptococcus pneumoniae-associated hemophagocytic lymphohistiocytosis in children / 中华儿科杂志

Objective: To summarize the clinical features of Streptococcus pneumoniae-associated hemophagocytic syndrome (SP-HLH), and the serotypes and drug-resistant characteristics of the isolated strains. Methods: There were 15 children with SP-HLH admitted to the Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital, Capital Medical University from January 2013 to December 2020 were included in this study. Clinical data including children's general characteristics, clinical features, laboratory examinations, treatments, prognosis and the outcomes of follow-up by May 2021 were analyzed retrospectively. The serotypes and drug resistance of the isolated strains were identified. All children were divided into the clinical improvement group and the death group. Mann-Whitney U test, Fisher's exact test were used to compare the data of the two groups. Results: Among the 15 children with SP-HLH, 8 were males and 7 were females. The age of these children was 1.0 (1.0, 2.5) years. Regarding the primary infection, there were 9 cases of severe pneumonia, 3 cases of meningitis and 3 cases of blood stream infection. None of these children had received pneumoniae conjugate vaccine (PCV) and all of them were admitted to the PICU. Respiratory failure was observed in 10 patients, acute renal injury in 5, and hemolytic uremic syndrome in 3 patients. All children received glucocorticoids and high-dose intravenous immunogloblin (IVIG) in addition to anti-infective treatment. Eight of the children were cured while the other 7 died. The neutrophil count in the death group was lower than that in the clinical improvement group ((5.0 (1.7, 9.3) × 109 vs. 5.2 (3.4, 10.5) ×109/L, Z =-2.43, P<0.015), and the length of hospital stay and days of PICU stay in the death group were both shorter than those in the improvement group statistically (3 (1, 11) vs. 39 (34, 48) d, 2 (1, 4) vs. 19 (12, 31) d, Z=-3.25, -3.24, both P=0.001). Ten serotypes of Streptococcus pneumoniae were identified, including 4 strains of 19F, 3 of 19A, 1 of 23F, 1 of 15A and 1 of 14, among which 9 strains (9/10) were covered by PCV13. All strains were resistant to erythromycin yet sensitive to vancomycin and linezolid. Conclusions: SP-HLH is more common in children under the age of 3, with a high mortality rate. The death cases have lower neutrophil count and rapid disease progression. The comprehensive treatment is anti-infective combined with glucocorticoids and high-dose IVIG. The predominant serotypes are 19F and 19A and all isolated strains were susceptible to vancomycin and linezolid.

Learning from the past: the history of human monkeypox and the atypical multi-country outbreak in 2022 / 中国当代儿科杂志

In 2022, the outbreak of human monkeypox (HMPX) occurred in many non-endemic countries. World Health Organization (WHO) assesses that this outbreak is "atypical". The history of monkeypox and HMPX must be reviewed to clearly recognize the "typical" outbreaks to fully understand this comment. Therefore, this paper reviews the epidemiological history of monkeypox, especially HMPX, and discusses and analyzes the atypical manifestations and the possible causes of the present outbreak based on the recent views of WHO, other organizations/institutions, and experts. The text describes the thought-provoking history of the interaction between the monkeypox virus and the human being in the past 64 years, and provides various information and views on the outbreak of HMPX, which is helpful to understand risk assessment and the potential impact of this outbreak on clinical and public health in future.

The investigation on the acute, severe hepatitis of unknown origin in children / 中国当代儿科杂志

In April 2022, the United Kingdom notified the World Health Organization (WHO) of an unexpected increase of acute hepatitis of unknown origin in children. Subsequent investigations have found more than 400 cases in more than 20 countries and regions around the world. Although the potential role of adenovirus type 41 in the pathogenesis of these cases is one hypothesis, but it is probably not the only pathogenic factor, and other infectious and non-infectious causes cannot be completely ruled out. For hepatitis caused by non-hepatitis A, B, C, D and E viruses, there is a lack of systematic monitoring and research, and many unknowns still exist. According to the current etiology speculation and epidemiological characteristics of adenovirus in China, cases of acute hepatitis with unknown origin may be found in China in the future. There is also a risk of imported cases. This article systematically sorts out the reports and studies on child acute hepatitis of unknown origin, hoping to attract the attention of pediatric clinicians in China, raise awareness and vigilance, and calmly prepare for possible abnormal situations.

Research advances in the treatment strategies for severe pertussis in children / 中国当代儿科杂志

At present, effective antibiotics and comprehensive symptomatic/supportive treatment as early as possible are mainly used for the treatment of severe pertussis in clinical practice. However, some children with severe pertussis have unsatisfactory response to commonly used drugs and treatment measures in the intensive care unit and thus have a high risk of death. Studies have shown that certain treatment measures given in the early stage, such as exchange transfusion, may help reduce deaths, but there is still a lack of uniform implementation norms. How to determine the treatment regimen for severe pertussis and improve treatment ability remains a difficult issue in clinical practice. This article reviews the advances in the treatment of severe pertussis, in order to provide a reference for clinical treatment and research.

A comparative analysis of the Chinese and English descriptions of typical pertussis manifestations and recommendations for the diagnosis of pertussis-like or pertussis syndrome / 中国当代儿科杂志

The Chinese and English names of pertussis or whooping cough show the important clinical features of the disease in terms of its course and cough characteristics respectively. In the clinical description of typical pertussis, the meanings of the Chinese and English words are not completely consistent, such as spastic cough versus paroxysmal cough, spasmodic stage/phase versus paroxysmal stage/phase, and "back-hook" versus whoop, and some descriptions in English are not seen in Chinese. This article aims to provide more comprehensive information for the understanding of pertussis by comparing the descriptions of typical clinical manifestations of pertussis in Chinese and English literatures and to put forward suggestions for the diagnosis of pertussis syndrome based on typical clinical manifestations.

Complications of pertussis / 中国当代儿科杂志

Patients with pertussis can have a variety of complications, including pneumonia and subconjunctival hemorrhage. Severe complications, such as pulmonary hypertension and encephalopathy, can be life-threatening. Younger children with pertussis may lack the characteristic clinical manifestations of pertussis, and therefore, a deeper understanding of the complications of pertussis may help to improve the diagnosis, treatment, and prognosis of pertussis. However, there is still no standard for the diagnosis and treatment of pertussis complications, and there are great differences in diagnostic name, basis, and data used in different reports. This article reviews the complications of pertussis which have been reported so far, such as pulmonary complications (pneumonia, pulmonary hypertension, pneumothorax, and mediastinal or subcutaneous emphysema), fractures, hernias, circulatory system complications, nervous system complications (convulsion, encephalopathy, hemorrhage, and hematoma), urinary system complications, and secondary infections, so as to provide a reference for the clinical diagnosis and treatment of pertussis complications, scientific research on pertussis complications, and the promotion of standardized diagnosis and treatment of pertussis complications.

Epidemiological and clinical features of vaccine-preventable diseases in vaccine era / 中国当代儿科杂志

In countries and regions with high vaccination coverage, several vaccine-preventable diseases have been resurged in recent years, such as measles, varicella, pertussis and mumps. Some studies have found that the clinical manifestation and epidemiological characteristics of these diseases were different from those in pre-vaccine era. This article reviewed the clinical and epidemiological features of vaccine-preventable diseases before and after wide immunization implementation, focusing on the situation in China, in order to attract the attention of clinicians, raise awareness, strengthen prevention and control, and promote in-depth research for these diseases.

Antimicrobial susceptibility and antigen genotypes of Bordetella pertussis strains isolated from neonates / 中国当代儿科杂志

OBJECTIVE@#To investigate the alternative antimicrobial drugs for the treatment of neonatal pertussis and the antigen genotypes of Bordetella pertussis (B. pertussis) strains.@*METHODS@#A total of 32 B. pertussis strains isolated from neonates between May 2013 and July 2018 were used in this study. E-test stripes were used to measure the minimal inhibitory concentration (MIC) of 18 antimicrobial drugs including erythromycin, sulfamethoxazole-trimethoprim (SMZ) and ampicillin. The 23S rRNA gene of isolated strains was amplified and sequenced to identify the mutation site of erythromycin resistance gene, and the seven antigen genotypes of B. pertussis strains (ptxA, ptxC, ptxP, prn, fim2, fim3 and tcfA2) were analyzed.@*RESULTS@#Of the 32 B. pertussis strains, 25 (78%) were resistant to erythromycin, azithromycin, clarithromycin and clindamycin, with an MIC of >256 mg/L, and A2047G mutation was observed in the 23S rRNA gene. All strains had an MIC of ≤0.064 mg/L for SMZ. The MIC of ampicillin, amoxicillin, amoxicillin-clavulanic acid and ceftriaxone ranged from 0.032 to 1 mg/L. The strains resistant to macrolide antibiotics had an antigen genotype of ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2.@*CONCLUSIONS@#B. pertussis strains from neonates are often resistant to macrolides, and the in vitro test shows that off-label use of sulfonamides is a reliable regimen for the treatment of neonates with macrolide-resistant pertussis. The prevalence of drug-resistant strains further emphasizes the importance of immunoprophylaxis.

Prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features / 中国当代儿科杂志

OBJECTIVE@#To investigate the prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features.@*METHODS@#A total of 106 children who were treated at the outpatient service or hospitalized from January 1, 2016 to May 31, 2017 were enrolled. Their nasopharyngeal swabs and venous blood samples were collected for Bordetella pertussis culture, multiple PCR and serum anti-pertussis toxin antibody detection. According to these results, the children were divided into pertussis group with 26 children and control group with 80 children, and clinical features were analyzed for both groups. E-test stripes were used to determine the sensitivity of Bordetella pertussis strains to erythromycin, azithromycin, doxycycline, levofloxacin, sulfamethoxazole/trimethoprim and amoxicillin.@*RESULTS@#Of the 106 children with chronic cough, 26 (24.5%) were found to have Bordetella pertussis infection. There were no significant differences in the incidence rates of typical symptoms of pertussis between the pertussis and control groups (P>0.05). E-test showed that erythromycin and azithromycin had a minimal inhibitory concentration (MIC) of >256 mg/L against five Bordetella pertussis strains, while amoxicillin had an MIC of 0.5-1 mg/L.@*CONCLUSIONS@#The presence of Bordetella pertussis infection in children with chronic cough should be taken seriously by clinicians, and children with chronic cough and Bordetella pertussis infection may not have the typical symptoms of pertussis and are mainly manifested as chronic cough. Amoxicillin may be an alternative drug for macrolide-resistant Bordetella pertussis infection.

Some thoughts on influenza vaccine and regular influenza vaccination for healthcare workers / 中国当代儿科杂志

It has been 100 years since the 1918 influenza pandemic but influenza is still an uncontrolled infectious disease. In some developed countries, the coverage rate of influenza vaccine can reach as high as 60%-70%, and even up to 90% or higher in some specific population, such as the elderly and healthcare workers. The coverage rate of influenza vaccination in Chinese people, however, is very low, only about 2%-3% per year. The limitations of influenza vaccine, and the purpose and significance of influenza vaccination, the imbalance of vaccine information and the importance of inoculation for healthcare workers are discussed in this paper. The resistance to popularize influenza vaccination is explored from different perspectives. It is hoped that more people will recognize the objective epidemiological data, and get rid of misunderstandings based on their experiences. Healthcare workers in particular, and the general population, should be encouraged to have an influenza vaccination.

Enhance research, prevention and control of pertussis for protecting public confidence in vaccination: focus on the adverse events of vaccine with insufficient potency and its long-term impacts / 中国当代儿科杂志

On November 3, 2017, the China Food and Drug Administration reported that the potency indexes of two batches of diphtheria-pertussis-tetanus vaccines produced by two companies did not reach the requirements. Insufficient potency could affect the protection effect of these vaccines immunization. Currently, pertussis cases have already showed an increasing trend in China and could last for several years. Such an increase could be linked to these adverse events of vaccine with insufficient potency, which could become an evidence to challenge or deny the effectiveness of vaccination, and brings a persistent inhibition of the public's acceptance for vaccination. The wider global context of pertussis resurgence, previous underestimate on the domestic pertussis, the promotion of detection methods, the change of knowledge about pertussis, the confirmation of pertussis in elder children and adults, the antigenicity variation of pertussis strains could lead to a significant increase of pertussis cases. Health researchers and clinical workers should raise awareness about these factors, and assess rationally the impact of vaccine titer deficiency on pertussis epidemiology for maintaining and promoting public confidence in vaccination.

Pertussis diagnosis: the limitation of the currently used criteria and the suggestion of Global Pertussis Initiative / 中国当代儿科杂志

It has been recognized that pertussis is a disease that affects all age groups. There are obvious limitations in the currently used diagnostic criteria with "one-size-fits-all" definition, which is not advantageous to start individual treatment and perform strategies for preventing the transmission. Therefore, the expert group of Global Pertussis Initiative gives a suggestion for the diagnosis of pertussis. Based on the related published studies, the present article analyzes the limitations of the current criteria, and introduces the GPI's suggestion in detail.

Prevalence of Moraxella catarrhalis in the nasopharyngeal specimen from 1 082 hospitalized children with respiratory infection and the drug resistance of the isolates / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of Moraxella catarrhalis in the nasopharyngeal region of children with respiratory infection and the sensitivity of Moraxella catarrhalis isolates to common antimicrobial drugs.</p><p><b>METHODS</b>Nasopharyngeal swabs were collected from 1 082 children with respiratory infection, and Moraxella catarrhalis strains were isolated. The E-test method and disc diffusion test were used to determine the sensitivity of these strains to 11 common antimicrobial drugs. The test results were interpreted with reference to the standards of European Committee on Antimicrobial Susceptibility Testing (EUCAST), Clinical and Laboratory Standards Institute (CLSI), and British Society for Antimicrobial Chemotherapy (BSAC). The nitrocefin disc method was used to detect whether the isolated strains produced β-lactamase.</p><p><b>RESULTS</b>Among the 1 082 children with respiratory infection, 77 (77/1 082, 7.12%) carried Moraxella catarrhalis in the nasopharyngeal region. All the strains produced β-lactamase. With reference to all the three standards, all the strains were sensitive to amoxycillin-clavulanate and had a susceptibility rate of >95% towards ciprofloxacin and tetracycline. According to the EUCAST and CLSI standards, the susceptibility rate of the strains towards sulfamethoxazole-trimethoprim was as high as 98.7%, and more than 80% of all strains were sensitive to the three cephalosporins detected; however, with reference to the BSAC standard, only 2.6% of the strains were sensitive to cefuroxime, with an intermediate rate of 44.2% and a drug resistance rate of 53.2%. The rate of resistance to ampicillin was 81.8%. According to the CLSI standard, the non-susceptibility rate of the strains to erythromycin was 79.2%, and according to the EUCAST or BSAC standards, their non-susceptibility rate reached 90.9%; more than one third of the strains (27/77, 35.1%) had a minimal inhibitory concentration of >256 mg/L.</p><p><b>CONCLUSIONS</b>All of the Moraxella catarrhalis isolates in the nasopharyngeal region of children with respiratory infection produce β-lactamase and are sensitive to amoxycillin-clavulanate. These isolates have high susceptibility rates to the third- and fourth-generation cephalosporins and sulfamethoxazole-trimethoprim, but most of the isolates are resistant to ampicillin, cefuroxime, and erythromycin.</p>

Adverse events following immunization and causality assessment of an adverse event following immunization / 中国当代儿科杂志

Several fatal events occurred in Hunan, Guangdong and Sichuan Province in December, 2013. The events were reported by the news media, which followed growing public concern. Currently, more and more vaccines were developed and the immunization was adopted for more objectives. The clinicians, especially pediatricians will face a growing number of clinical problems related to the vaccine. The clinicians should pay attention to learn more knowledge about vaccines. This article describes the definition and classification of "adverse events following immunization" and "serious vaccine product-related reactions", and the signifcance and conclusion of causality assessment following immunization.

The ambitious but achievable goal: to end preventable childhood deaths due to pneumonia by 2025 / 中国当代儿科杂志

Globally, pneumonia is the leading cause of childhood mortality. Pneumonia is the second killer of children less than 5 years of age in China. The World Heath Organization and United Nations Children′s Fund launched the integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD) in 2013. The ambitious goal is to end preventable childhood deaths due to pneumonia by 2025. Countries or regions should achieve the following goals: (1) reduce mortality from pneumonia in children less than 5 years of age to fewer than 3 per 1 000 live births; (2) reduce the incidence of severe pneumonia by 75% in children less than 5 years of age compared to 2010 levels. If the implementation of key interventions is accelerated, the mortality rate of childhood pneumonia will drop substantially every year, which makes the goal achievable.

Clinical characteristics of whooping cough in neonates and antimicrobial resistance of the pathogenic bacteria / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of whooping cough in neonates and the antimicrobial resistance of the bacterial isolates.</p><p><b>METHODS</b>Clinical information of 7 neonates with whooping cough confirmed by bacterial culture was collected. The antimirobial resistance of the isolates was tested using E-test and disk diffusion methods.</p><p><b>RESULTS</b>The children′s mothers or other family members had cough for more than 10 days in 6 neonates, in which four neonates contacted with 3 or more family members with cough. All the neonates had rhinobyon and slight cough at the beginning of the disease. Five cases presented typical spasmodic cough after 4-7 days of the onset. Five cases displayed cyanosis, four cases occurred apnea, three cases suffered breath holding, and only two cases had fever. Nares flaring and three depression signs were found in the physical examination. No bacteriostatic ring around the erythromycin disks were found for five bacterial isolates. The minimal inhibitory concentration (MIC) for erythromycin, azithromycin, clarithromycin and clindamycin were all >256 mg/L against the five isolates.</p><p><b>CONCLUSIONS</b>Whooping cough should be considered for neonates with respiratory symptoms and a history of close contact with respiratory infection patients. Macrolide-resistant Bordetella pertussis is common in children with whooping cough.</p>