Patterns of antibiotic administration in Chinese neonates: results from a multi-center, point prevalence survey.

OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.

Concordance in pathogen identification at the upper and lower respiratory tract of children with severe pneumonia.

BACKGROUND: Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear. METHODS: Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR. RESULTS: The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs. CONCLUSION: The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid.

Talaromyces marneffei infection and complicate manifestation of respiratory system in HIV-negative children.

BACKGROUND: Respiratory symptoms are the earliest clinical manifestation of Talaromyces marneffei (TM) infection. In this study, we aimed to improve the early identification of TM infection in human immunodeficiency virus (HIV)-negative children with respiratory symptoms as the first manifestation, analyze the risk factors, and provide evidence for diagnosis and treatment. METHODS: We retrospectively analyzed six cases of HIV-negative children with respiratory system infection symptoms as the first presentation. RESULTS: All subjects (100%) had cough and hepatosplenomegaly, and five subjects (83.3%) had a fever; other symptoms and signs included lymph node enlargement, rash, rales, wheezing, hoarseness, hemoptysis, anemia, and thrush. Additionally, 66.7% of the cases had underlying diseases (three had malnutrition, one had severe combined immune deficiency [SCID]). The most common coinfecting pathogen was Pneumocystis jirovecii, which occurred in two cases (33.3%), followed by one case of Aspergillus sp. (16.6%). Furthermore, the value of ß-D-glucan detection (G test) increased in 50% of the cases, while the proportion of NK decreased in six cases (100%). Five children (83.3%) were confirmed to have the pathogenic genetic mutations. Three children (50%) were treated with amphotericin B, voriconazole, and itraconazole, respectively; three children (50%) were treated with voriconazole and itraconazole. All children were tested for itraconazole and voriconazole plasma concentrations throughout antifungal therapy. Two cases (33.3%) relapsed after drug withdrawal within 1 year, and the average duration of antifungal treatment for all children was 17.7 months. CONCLUSION: The first manifestation of TM infection in children is respiratory symptoms, which are nonspecific and easily misdiagnosed. When the effectiveness of anti-infection treatment is poor for recurrent respiratory tract infections, we must consider the condition with an opportunistic pathogen and attempt to identify the pathogen using various samples and detection methods to confirm the diagnosis. It is recommended the course for anti-TM disease be longer than one year for children with immune deficiency. Monitoring the blood concentration of antifungal drugs is important.

Comparison of 11 respiratory pathogens among hospitalized children before and during the COVID-19 epidemic in Shenzhen, China.

BACKGROUND: The effect of SARS-CoV-2 on existing respiratory pathogens in circulation remains uncertain. This study aimed to assess the impact of SARS-CoV-2 on the prevalence of respiratory pathogens among hospitalized children. METHODS: This study enrolled hospitalized children with acute respiratory infections in Shenzhen Children's Hospital from September to December 2019 (before the COVID-19 epidemic) and those from September to December 2020 (during the COVID-19 epidemic). Nasopharyngeal swabs were collected, and respiratory pathogens were detected using multiplex PCR. The absolute case number and detection rates of 11 pathogens were collected and analyzed. RESULTS: A total of 5696 children with respiratory tract infection received multiplex PCR examination for respiratory pathogens: 2298 from September to December 2019 and 3398 from September to December 2020. At least one pathogen was detected in 1850 (80.5%) patients in 2019, and in 2380 (70.0%) patients in 2020; the detection rate in 2020 was significantly lower than that in 2019.The Influenza A (InfA) detection rate was 5.6% in 2019, but 0% in 2020. The detection rates of Mycoplasma pneumoniae, Human adenovirus, and Human rhinovirus also decreased from 20% (460), 8.9% (206), and 41.8% (961) in 2019 to 1.0% (37), 2.1% (77), and 25.6% (873) in 2020, respectively. In contrast, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased from 6.6% (153), 9.9% (229), and 0.5% (12) in 2019 to 25.6% (873), 15.5% (530), and 7.2% (247) in 2020, respectively (p < 0.0001). CONCLUSIONS: Successful containment of seasonal influenza as a result of COVID-19 control measures will ensure we are better equipped to deal with future outbreaks of both influenza and COVID-19.Caused by virus competition, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased in Shenzhen,that reminds us we need to take further monitoring and preventive measures in the next epidemic season.

Broad range detection of viral and bacterial pathogens in bronchoalveolar lavage fluid of children to identify the cause of lower respiratory tract infections.

BACKGROUND: Knowledge on the etiology of LRTIs is essential for improvement of the clinical diagnosis and accurate treatment. Molecular detection methods were applied to identify a broad range of bacterial and viral pathogens in a large set of bronchial alveolar lavage (BAL) fluid samples. The patterns of detected pathogens were correlated to the clinical symptoms. METHODS: BAL fluid samples and clinical data were collected from 573 hospitalized children between 1 month and 14 years of age with LRTIs, enrolled from January to December 2018. Pathogens were detected using standardized clinical diagnostics, with a sensitive, high-throughput GeXP-based multiplex PCR and with multiplex qPCR. Data were analyzed to describe the correlation between the severity of respiratory tract disease and the pathogens identified. RESULTS: The pathogen detection rate with GeXP-based PCR and multiplex qPCR was significantly higher than by clinical routine diagnostics (76.09% VS 36.13%,χ2 = 8.191, P = 0.004). The most frequently detected pathogens in the BAL fluid were human adenovirus (HADV)(21.82%), Mycoplasma pneumoniae (20.24%), human rhinovirus (13.96%), Streptococcus pneumoniae (8.90%) and Haemophilus influenzae (8.90%). In 16.4% of the cases co-detection with two or three different pathogens was found. Viral detection rates declined with age, while atypical pathogen detection rates increased with age. Oxygen supply in the HADV and Influenza H1N1 infected patients was more frequent (49.43%) than in patients infected with other pathogens. CONCLUSION: Broad range detection of viral and bacterial pathogens using molecular methods is a promising and implementable approach to improve clinical diagnosis and accurate treatment of LRTI in children.

[Clinical features of sleep-disordered breathing in children with neuromuscular disease].

OBJECTIVE: To study the clinical features of sleep-disordered breathing (SDB) in children with neuromuscular disease (NMD). METHODS: A retrospective analysis was performed on the medical data of 18 children who were diagnosed with NMD and underwent polysomnography (PSG) (NMD group). Eleven children without NMD who had abnormal sleeping habit and normal sleep structure on PSG were enrolled as the control group. The two groups were compared in terms of the daily and nocturnal symptoms of SDB, incidence rate of obstructive sleep apnea (OSA), pulmonary function, end-tidal partial pressure of carbon dioxide (PetCO2), features of sleep structure, and sleep respiratory events. RESULTS: In the NMD group, 16 children (89%) had related daily and nocturnal symptoms of SDB, and the youngest age was 1 year at the onset of such symptoms. Compared with the control group, the NMD group had significant reductions in total sleep time and sleep efficiency (P < 0.05), a significant reduction in the proportion of rapid eye movement (REM) sleep (P < 0.05), significant increases in obstructive apnea and hypopnea events (P < 0.05) and oxygen reduction events during REM sleep (P < 0.05), and a significant reduction in blood oxygen saturation during REM sleep (P < 0.05). In the NMD group, 17 children (94%) were diagnosed with OSA, and all children had normal lung function and PetCO2. CONCLUSIONS: There is a high proportion of children with SDB among the children with NMD, and SDB can be observed in the early stage of NMD, which results in the damage of sleep structure and the reduction in sleep efficiency. Respiratory events are mainly obstructive events, and oxygen reduction events are mainly observed during REM sleep.

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OBJECTIVES: To study the clinical features of obstructive sleep apnea (OSA) in children with obesity. METHODS: A retrospective analysis was performed on the medical data of 33 obese children aged 7-15 years, who were diagnosed with OSA and received polysomnography (PSG) in the Department of Respiratory Medicine in Shenzhen Children's Hospital. Fifty OSA children with normal body weight, matched for sex and age, were enrolled as the control group. RESULTS: Among the 33 obese children with OSA, the three most common daytime symptoms were inattention in 30 children (91%), somnolence in 22 children (67%), and morning fatigue in 21 children (64%), and the three most common nocturnal symptoms were snoring in 27 children (82%), mouth breathing in 20 children (61%), and sweating in 16 children (49%). Compared with the reference values of normal children, both the OSA + obesity group and the control group had prolonged light sleep, shortened deep sleep, and a significantly shortened rapid eye movement (REM) period, while there was no significant difference in these indices between the two groups (P>0.05). The apnea-hypopnea index, obstructive apnea/hypopnea index, and oxygen desaturation index in both REM and non-REM periods in the OSA +obesity group were significantly higher than those in the control group (P<0.05), while the lowest blood oxygen saturation during sleep was significantly lower in the OSA + obesity group (P<0.05). CONCLUSIONS: The children with obesity and OSA have the main daytime symptoms of inattention, somnolence, and morning fatigue and the main nocturnal symptoms of snoring, mouth breathing, and sweating. There is no significant difference in sleep structure between OSA children with obesity and those with normal body weight; however, respiratory events and blood oxygen saturation decline are more severe in OSA children with obesity. Citation.

Different nasopharynx and oropharynx microbiota imbalance in children with Mycoplasma pneumoniae or influenza virus infection.

BACKGROUND: The Mycoplasma pneumoniae(MP) and influenza virus are two common pathogens causing pediatric acute respiratory tract infection. Though emerging reports demonstrated imbalanced respiratory microbiota in respiratory infection, the respiratory microbiota differences between MP and influenza virus remained to be explored. METHODS: We collected paired nasopharyngeal(NP) and oropharyngeal(OP) microbial samples from 165 children, including 40 patients with MP pneumonia, 66 patients with influenza virus infection and 59 age-matched healthy children. RESULTS: The NP and OP microbial diversity decreased in MP infection and increased in influenza infection as compared to healthy children. The Staphylococcus dominated Mycoplasma pneumoniae pneumonia(MPP) patients' NP microbiota while five representative patterns remained in influenza patients. In OP microbiota, Streptococcus significantly enriched in MPP group and decreased in Influenza group. Decision tree analysis indicated that Ralstonia and Acidobacteria could discriminate microbial samples in healthy (59/67), MP (35/38) and Influenza groups (55/60) with high accuracy. CONCLUSIONS: This study revealed that dominant bacterial structure in the airway was niche- and disease-specific. It could facilitate the stratification of respiratory microbial samples with different infectious agents.

[Clinical features of children with influenza and plastic bronchitis: an analysis of 63 cases].

OBJECTIVE: To study the clinical features of children with influenza and plastic bronchitis (PB). METHODS: A retrospective analysis was performed on the medical data of 63 children with influenza and PB, including clinical manifestations, laboratory examination results, imaging findings, treatment, and outcome. RESULTS: Among the 63 children, there were 52 boys (83%) and 11 girls (17%), and 42 children had influenza A and 21 had influenza B. Among these children, 38 (60%) aged 3-6 years, and 15 (24%) had underlying diseases. The main clinical manifestations were high fever (90%), cough (95%), and shortness of breath (73%). Twenty-four children (38%) were found to have atelectasis by imaging examination. Auscultation showed that 16 children (25%) had no rales in the lungs. Of all children, 41 were admitted to the intensive care unit, and 32 required mechanical ventilation. All children underwent fiberoptic bronchoscopy and alveolar lavage. Among the 63 children, 60 recovered and 3 died. CONCLUSIONS: Influenza with PB is often observed in boys and preschool children. For influenza children with shortness of breath, even if there is no atelectasis on chest X-ray or no rales are found by auscultation, the possibility of PB still needs to be considered.

[Clinical features of influenza with plastic bronchitis in children].

OBJECTIVE: To study the clinical features of influenza with plastic bronchitis (PB) in children, and to improve the awareness of the diagnosis and treatment of PB caused by influenza virus. METHODS: A retrospective analysis was performed for the clinical data of 70 children with lower respiratory influenza virus infection from October 2018 to October 2019. According to the presence or absence of PB, they were divided into an influenza+PB group with 12 children and a non-PB influenza group with 58 children. Related clinical data were collected for the retrospective analysis, including general information, clinical manifestations, laboratory examination, imaging findings, treatment, and prognosis. RESULTS: In the influenza+PB group, most children experienced disease onset at the age of 1-5 years, with the peak months of January, February, July, and September. Major clinical manifestations in the influenza+PB group included fever, cough, and shortness of breath. The influenza+PB group had significantly higher incidence rates of shortness of breath and allergic diseases such as asthma than the non-PB influenza group (P<0.05). Of the 12 children in the influenza+PB group, 7(58%) had influenza A virus infection and 5 (42%) had influenza B virus infection, among whom 1 had nephrotic syndrome. For the children in the influenza+PB group, major imaging findings included pulmonary consolidation with atelectasis, high-density infiltration, pleural effusion, and mediastinal emphysema. Compared with the non-PB influenza group, the influenza+PB group had a significantly higher proportion of children who were admitted to the pediatric intensive care unit (P<0.05). Bronchoscopic lavage was performed within 1 week after admission, and all children were improved and discharged after anti-infective therapy and symptomatic/supportive treatment. CONCLUSIONS: Influenza with PB tends to have acute onset and rapid progression, and it is important to perform bronchoscopy as early as possible. The possibility of PB should be considered when the presence of shortness of breath, allergic diseases such as asthma or nephrotic syndrome in children with influenza.

Prevalence of respiratory viruses among children hospitalized from respiratory infections in Shenzhen, China.

BACKGROUND: The prevalence of local dominant viral etiologies is important for clinical management and prevention of common viral respiratory tract infections. Unfortunately, there is limited large-scale data about common viral respiratory infection in south China. To survey dominant viral etiology and seasonality of acute respiratory infections in hospitalized children, a 4-year consecutive study was conducted in Shenzhen, China. METHODS: Nasopharyngeal swab specimens were obtained from 30,443 hospitalized children younger than 14 years with respiratory tract diseases in Shenzhen Children's Hospital from January 2012 to December 2015. Nasopharyngeal swabs were routinely examined by direct immunofluorescence assay to detect respiratory agents including seven respiratory viruses. Data were analyzed to describe the frequency and seasonality. RESULTS: Of the 30,443 children enrolled in the study, 4428 (14.55 %) were positive for at least one viral pathogen, among whom 4110 (92.82 %) were ≤3 years of age. The predominant viruses were respiratory syncytial virus (RSV, 68.11 %), adenovirus (ADV, 16.01 %) and parainfluenza virus 3 (PIV-3, 11.0 %). The common respiratory viruses detected peaked in the spring (17.69 %), and were minimal in autumn (9.73 %), but PIVs detection peaked in November. The common virus detection rate in male subjects (15.40 %) was significantly higher than in female subjects (13.02 %). PIVs detection rates were complementary with RSV in autumn in each year. CONCLUSIONS: This study demonstrated common respiratory viruses were the major cause of hospitalized acute respiratory infection (ARI) in children in Shenzhen, China. RSV was the most common detected infection, while ADV was the predominant pathogen in hospitalized children. These findings provide a better understanding of virus distribution among children of different ages, infection stratification by gender, and seasonality, all of which will contribute to modification of therapeutic approaches and development of effective prevention strategies for each respiratory virus infection during peak seasons.

Uncontrolled asthma and its risk factors in Chinese children: A cross-sectional observational study.

OBJECTIVE: Asthma afflicts many children in China but information about asthma management among Chinese pediatric asthma patients is limited. This study aims to evaluate asthma control among Chinese pediatric patients and identify risk factors associated with uncontrolled asthma. METHODS: A total of 4223 patients with persistent asthma aged 2-16 years from 42 tertiary hospitals across all regions of mainland China except Tibet were surveyed. Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT) and Global Initiative for Asthma (GINA) criteria were used to assess asthma control for children aged 12-16 years, 4-11 years and 2-3 years, respectively. Uncontrolled asthma was defined as ACT or C-ACT score ≤19 or GINA-defined uncontrolled asthma. Risk factors associated with uncontrolled asthma were identified using multivariate logistic regression models. RESULTS: Asthma was uncontrolled in 19.9% of the subjects. High rates of uncontrolled asthma were found in subjects with treatment non-adherence (44.1%), concomitant allergic rhinitis (AR) (23.3%), disease duration ≥ 1.5 years (22.8%), and first-degree relatives with AR (21.5%). The risk of uncontrolled asthma was much higher in the treatment non-adherence group compared to the complete adherence group (OR = 5.79, p < 0.001). Concomitant AR, disease duration ≥ 1.5 years, and first-degree relatives with AR were also confirmed as risk factors associated with uncontrolled asthma. CONCLUSIONS: About 20% of Chinese pediatric asthma patients had uncontrolled asthma. Treatment adherence and AR were the most significant risk factors. Tailored measures aimed at improving treatment adherence and diagnosis and treatment of AR should be adopted to improve the level of asthma control in Chinese children.

Clinical and molecular characteristics of invasive community-acquired Staphylococcus aureus infections in Chinese children.

BACKGROUND: This study aims to investigate the clinical features of invasive community-acquired Staphylococcus aureus (CA-SA) infection in Chinese children and analyze its molecular features. METHODS: Clinical data and invasive CA-SA isolates were prospectively collected. Pediatric risk of mortality (PRISM) score was used for disease severity measurement. Molecular typing was then performed, followed by expression analysis for virulence genes. RESULTS: Among 163 invasive CA-SA infection cases, 71 (43.6%) were methicillin-resistant SA (MRSA) infections and 92 (56.4%) were methicillin-susceptible SA (MSSA). A total of 105 (64.4%) children were younger than 1 year old, and 79.7% (129/163) were under 3 years age. Thirteen kinds of diseases were observed, in which bacteremia and pneumonia accounted for 65.6% (107/163) and 52.8% (86/163), respectively. A total of 112 (68.1%) patients had two or more infective sites simultaneously, and four cases (2.5%) died. CA-MSSA more frequently caused multi-sites infections, bacteremia, and musculoskeletal infection than MRSA. A total of 25 sequence types (STs) were detected. MRSA mainly comprised ST59 (49/71, 69%), whereas the most frequent clonotypes were ST88 (15/92, 16.3%), ST25 (13/92, 14.1%), ST7 (13/92, 14.1%), ST2155 (12/92, 13%), and ST188 (9/92, 9.8%) for MSSA. Seven STs were common to both MSSA and MRSA groups. No differences in clinical presentation or PRISM score were found between the two groups or among different ST. The expression levels of the four known virulence genes varied among the six main ST clones. CONCLUSIONS: Invasive CA-SA infections were characterized by high incidence and multi-site infections in young children in China. The clinical manifestations of CA-MSSA were more frequently associated with multi-site infections, bacteremia and musculoskeletal infection than those of CA-MRSA. Isolated genotypes may be relevant to the expressions of virulence genes, but not to clinical manifestations.

Exploring the Multifaceted Landscape of Pediatric Obstructive Sleep Apnea: Insights into Prevalence, Severity, and Coexisting Conditions.

Background: Pediatric obstructive sleep apnea (OSA) is a multifaceted disorder marked by recurrent upper airway obstruction during sleep, often coexisting with various medical conditions. This study, aimed to comprehensively analyze the Multifaceted Landscape of Pediatric Insights into Prevalence, Severity, and Coexisting Conditions. With a sample of 1928 participants, our study sought to determine the prevalence, severity, and associations between OSA and diverse conditions. Methods: Conducted retrospectively from February 2019 to April 2023, the study included pediatric patients. Data were collected through electronic health records, involving clinical assessments, medical histories, and diagnostic tests to establish OSA and coexisting condition diagnoses. Relationships between sleep parameters, apnea types, and severity indices were evaluated. Results: High OSA prevalence was evident across age groups, with severity peaking between 3 to 12 years. Among the participants, coexisting conditions included allergic rhinitis (59.6%), tonsillar hypertrophy (49.7%), adenoid hypertrophy (28.4%), and obesity (15.3%). Analysis revealed intriguing relationships between different sleep parameters and apnea types. Notable associations were observed between Obstructive Apnea (OA) and Central Apnea (CA), and Mixed Apnea (MA) displayed associations with both OA and CA. Hypopnea correlated directly with the Apnea-Hypopnea Index (AHI), reflecting its role in OSA severity. Conclusion: This study provides a comprehensive understanding of the intricate dynamics between pediatric OSA and coexisting conditions. The prevalence of OSA and its coexistence with various conditions underscore the need for comprehensive evaluation and management strategies. By revealing associations between different sleep parameters and apnea types, the study emphasizes the complexity of OSA diagnosis and management. These findings hold the potential to enhance clinical approaches, ultimately leading to improved care and outcomes for affected children.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to ß-lactam antibiotics in a Chinese metropolitan city.

OBJECTIVES: We characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. METHODS: Seventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. RESULTS: These IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to ß-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. CONCLUSION: A novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Molecular characteristics and antimicrobial resistance of invasive pneumococcal isolates from children in the post-13-valent pneumococcal conjugate vaccine era in Shenzhen, China.

OBJECTIVES: This study aimed to evaluate the molecular epidemiology and antimicrobial resistance of invasive pneumococcal isolates from children in Shenzhen, China, in the early stage of the pneumococcal 13-valent conjugated vaccine (PCV-13) era from 2018 to 2020. METHODS: Invasive pneumococcal strains were isolated from hospitalized children with invasive pneumococcal diseases (IPDs) from January 2018 to December 2020. The serotype identification, multilocus sequence typing (MLST), and antibiotic susceptibility tests were performed on all culture-confirmed strains. RESULTS: Sixty-four invasive strains were isolated mainly from blood (70.3%). Prevalent serotypes were 23F (28.1%), 14 (18.8%), 19F (15.6%), 6A/B (14.1%), and 19A (12.5%), with a serotype coverage rate of 96.9% for PCV13. The most common sequence types (STs) were ST876 (17.1%), ST271 (10.9%), and ST320 (7.8%). Half of the strains were grouped in clonal complexes (CCs): CC271 (21.9%), CC876 (20.3%), and CC90 (14.1%). Meningitis isolates showed a higher resistance rate (90.9% and 45.5%) to penicillin and ceftriaxone than the rate (3.8% and 9.4%) of non-meningitis isolates. The resistance rates for penicillin (oral), cefuroxime, and erythromycin were 53.13%, 73.4%, and 96.9%, respectively. The dual ermB and mefA genotype was found in 81.3% of erythromycin-resistant strains. The elevated minimum inhibitory concentration (MIC) of ß-lactam antibiotics and dual-genotype macrolide resistance were related mainly to three major serotype-CC combinations: 19F-CC271, 19A-CC271, and 14-CC876. CONCLUSION: Invasive pneumococcus with elevated MICs of ß-lactams and increased dual ermB and mefA genotype macrolide resistance were alarming. Expanded PCV13 vaccination is expected to reduce the burden of paediatric IPD and to combat antibiotic-resistant pneumococcus in Shenzhen.

A review of penicillin binding protein and group A Streptococcus with reduced-ß-lactam susceptibility.

With the widespread use of antibiotics, antimicrobial resistance (AMR) has become a global problem that endangers public health. Despite the global high prevalence of group A Streptococcus (GAS) infections and the global widespread use of ß-lactams, ß-lactams remain the first-line treatment option for GAS infection. ß-hemolytic streptococci maintain a persistent susceptibility to ß-lactams, which is an extremely special phenomenon in the genus Streptococci, while the exact current mechanism is not known. In recent years, several studies have found that the gene encoding penicillin binding protein 2X (pbp2x) is associated with GAS with reduced-ß-lactam susceptibility. The purpose of this review is to summarize the current published data on GAS penicillin binding proteins and ß-lactam susceptibility, to explore the relationship between them, and to be alert to the emergence of GAS with reduced susceptibility to ß-lactams.

The rise and fall of acute rheumatic fever and rheumatic heart disease: a mini review.

Introduction: The incidences of acute rheumatic fever (ARF) and rheumatic heart disease (RHD), which were leading causes of death in children in the 1920s, have decreased substantially. Considering the recent resurgence of scarlet fever and increased incidence of streptococcal pharyngitis in children, an investigation of the current status of ARF and RHD may be worthwhile. Objective: To summarize the prevalence trends, pathogenic factors, and prevention strategies for ARF and RHD in children. Methods: A selective search of literature published between January 1920 and February 2023 was done in PubMed, using the terms "acute rheumatic fever", "rheumatic heart disease", "group A Streptococcus", "pharyngitis", "pharyngeal tonsillitis", "scarlet fever", "impetigo", "obstructive sleep apnea syndrome" and "child". Results: Overcrowded homes and inadequate sanitation led to recurrent group A streptococcal infection, and the causal relationship between group A streptococcal infection and ARF/RHD was well established. Streptococcal infectious diseases, such as group A streptococcal pharyngeal tonsillitis, SF, impetigo, and obstructive sleep apnea syndrome, were associated with the occurrence of ARF and RHD. ARF and RHD were still prevalent in young people of developing countries and economically poor populations of high-income countries. Universal disease registration systems were critical to locating disease outbreaks, tracking disease transmission, and identifying high-risk populations. Four-level prevention strategies were effective in reducing the incidence and mortality of ARF and RHD. Conclusions: Registry and preventive measures for ARF and RHD should be strengthened in areas of dense population; poor sanitation; resurgence of SF; and high incidence of streptococcal pharyngitis, impetigo, and obstructive sleep apnea syndrome.

Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics.

Background: To summarize the clinical features of severe influenza in children and the high-risk factors for influenza-related deaths and to raise awareness among pediatricians. Methods: A retrospective study of clinical manifestations, laboratory tests, and diagnosis and treatment of 243 children with severe influenza admitted to Shenzhen Children's Hospital from January 2009 to December 2022 was conducted. Univariate logistic regression analysis and Boruta analysis were also performed to identify potentially critical clinical characteristics associated with death, and clinically significant were used in further multivariate logistic regression analysis. Subject receiver operating characteristic (ROC) curves were applied to assess the efficacy of death-related independent risk factors to predict death from severe influenza. Results: There were 169 male and 74 female patients with severe influenza, with a median age of 3 years and 2 months and 77.4% of patients under six. There were 46 cases (18.9%) in the death group. The most common pathogen was Influenza A virus (IAV) (81.5%). The most common complication in the death group was influenza-associated acute necrotizing encephalopathy (ANE [52.2%]). Severe influenza in children decreased significantly during the COVID-19 pandemic, with a median age of 5 years, a high predominance of neurological symptoms such as ANE (P = 0.001), and the most common pathogen being H3N2 (P < 0.001). D-dimer, acute respiratory distress syndrome (ARDS), and acute necrotizing encephalopathy (ANE) were significant independent risk factors for severe influenza-associated death. Furthermore, the ROC curves showed that the combined diagnosis of independent risk factors had significant early diagnostic value for severe influenza-related deaths. Conclusion: Neurological disorders such as ANE are more significant in children with severe influenza after the COVID-19 pandemic. Influenza virus infection can cause serious multisystem complications such as ARDS and ANE, and D-dimer has predictive value for early diagnosis and determination of the prognosis of children with severe influenza.