Safety of Immunization for Children with Immune Thrombocytopenia.

Vaccine hesitancy is a common issue for children with immune thrombocytopenia (ITP) in China. The objective of this paper is to assess the immunization statuses of children with ITP, analyze the possible relationship between immunization and thrombocytopenia, and evaluate the safety of immunization after ITP remission. We included 186 children with an ITP history and followed up with them for two years after receiving re-immunization recommendations. The participants had an overall age-appropriate vaccine coverage of 57.9%. Vaccine-associated thrombocytopenia occurred in 99 (53.2%, 95% CI = 46.06-60.26) children ranging from 0 to 34 days following immunization, with 14 vaccines involved. One hundred and fifty-four (82.3%, 95% CI = 76.72-87.54) children were advised to restart immunization, whereas 32 (17.2%, 95% CI = 12.46-23.28) were advised to postpone partial or full vaccination. Following the follow-up, 150 (80.6%, 95% CI = 74.37-85.68) children completed the catch-up immunization, whereas 27 (14.5%, 95% CI = 10.17-20.30) partially completed it. Four patients with thrombocytopenia relapsed following the re-immunization. Incomplete catch-up immunization was related to the factors of chronic thrombocytopenia, vaccine-associated thrombocytopenia, and the relapse of ITP following re-immunization. ITP may occur after immunization with vaccines other than measles-containing vaccines. Re-immunization in children with ITP generally does not result in a relapse, regardless of whether the previous thrombocytopenia was vaccine-associated.

A Nationwide Genomic Study of Clinical Klebsiella pneumoniae Carrying blaOXA-232 and rmtF in China.

OXA-232 carbapenemase is becoming a threat in China due to its high prevalence, mortality, and limited treatment options. However, little information is available on the impact of OXA-232-producing Klebsiella pneumoniae in China. This study aims to characterize the clonal relationships, the genetic mechanisms of resistance, and the virulence of OXA-232-producing K. pneumoniae isolates in China. We collected 81 OXA-232-producing K. pneumoniae clinical isolates from 2017 to 2021. Antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular types, multilocus sequence types, virulence genes, antimicrobial resistance (AMR) determinants, plasmid replicon types, and single-nucleotide polymorphism (SNP) phylogeny were inferred from whole-genome sequences. OXA-232-producing K. pneumoniae strains were resistant to most antimicrobial agents. These isolates showed partial differences in susceptibility to carbapenems: all strains were resistant to ertapenem, while the resistance rates to imipenem and meropenem were 67.9% and 97.5%, respectively. Sequencing and capsular diversity analysis of the 81 K. pneumoniae isolates revealed 3 sequence types (ST15, ST231, and one novel ST [ST-V]), 2 K-locus types (KL112 and KL51), and 2 O-locus types (O2V1 and O2V2). The predominant plasmid replicon types associated with the OXA-232 and rmtF genes were ColKP3 (100%) and IncFIB-like (100%). Our study summarized the genetic characteristics of OXA-232-producing K. pneumoniae circulating in China. The results demonstrate the practical applicability of genomic surveillance and its utility in providing methods to prevent transmission. It alerts us to the urgent need for longitudinal surveillance of these transmissible lineages. IMPORTANCE In recent years, the detection rate of carbapenem-resistant K. pneumoniae has increased and represents a major threat to clinical anti-infective therapy. Compared with KPC-type carbapenemases and NDM-type metallo-ß-lactamases, OXA-48 family carbapenemases are another important resistance mechanism mediating bacterial resistance to carbapenems. In this study, we investigated the molecular characteristics of OXA-232 carbapenemase-producing K. pneumoniae isolated from several hospitals to clarify the epidemiological dissemination characteristics of such drug-resistant strains in China.

Ceftazidime-avibactam-based combination therapy for hospital-acquired central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Klebsiella pneumoniae (K. pneumoniae) is one of the most common bacteria in the hospital-acquired central nervous system (CNS) infections. Central nervous system infections caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with significant mortality rates and high hospital costs due to limited antibiotic treatment options. This retrospective study aimed to evaluate the clinical efficacy of ceftazidime-avibactam (CZA) for the treatment of CNS infections caused by CRKP. METHODS: Twenty-one patients with hospital-acquired CNS infections caused by CRKP who received treatment with CZA for ≥ 72 hours were enrolled. The primary outcome was to assess the clinical and microbiology efficacy of CZA for the treatment of CNS infections caused by CRKP. RESULTS: A high burden of comorbidity was discovered in 20 of 21 patients (95.2%). Most patients had a history of craniocerebral surgery and 17 (81.0%) of the patients were in the intensive care unit with a median APACHE II score of 16 (IQR 9-20) and SOFA score of 6 (IQR 3-7). Eighteen cases were treated by CZA-based combination therapies, while the remaining three cases were treated with CZA alone. At the end of the treatment, the overall clinical efficacy was 76.2% (16 of 21) with a bacterial clearance rate of 81.0% (17 of 21) and all-cause mortality of 23.8% (five of 21). CONCLUSION: This study showed that CZA-based combination therapy is an effective treatment option for CNS infections caused by CRKP.

A Novel Anti-CRISPR AcrIE9.2 Is Associated with Dissemination of blaKPC Plasmids in Klebsiella pneumoniae Sequence Type 15.

Sequence type (ST) 15 has become an emerging clone of carbapenem-resistant Klebsiella pneumoniae in which type I-E* CRISPR-Cas usually exists, indicating that the CRISPR-Cas system may not be able to block the transfer of blaKPC plasmids. The purpose of this study was to explore the mechanisms underlying dissemination of blaKPC plasmids in K. pneumoniae ST15. The type I-E* CRISPR-Cas system was present in 98.0% of 612 nonduplicate K. pneumoniae ST15 strains (88 clinical isolates and 524 from the NCBI database). Twelve ST15 clinical isolates were completely sequenced, and self-targeted protospacers were found on blaKPC plasmids flanked by a protospacer adjacent motif (PAM) of AAT in 11 isolates. The type I-E* CRISPR-Cas system was cloned from a clinical isolate and expressed in Escherichia coli BL21(DE3). In BL21(DE3) harboring the CRISPR system, the transformation efficiency of protospacer-bearing plasmids with a PAM of AAT was reduced by 96.2% compared to the empty vector, indicating that the type I-E* CRISPR-Cas system impeded blaKPC plasmid transfer. BLAST for known anti-CRISPR (Acr) amino acid sequences uncovered a novel AcrIE9-like protein with 40.5% to 44.6% sequence identity with AcrIE9 designated AcrIE9.2, which was present in 90.1% (146 of 162) of ST15 strains carrying both blaKPC and the CRISPR-Cas system. When AcrIE9.2 was cloned and expressed in a ST15 clinical isolate, the conjugation frequency of a CRISPR-targeted blaKPC plasmid was increased from 3.96 × 10-6 to 2.01 × 10-4 compared to the AcrIE9.2 absent strain. In conclusion, AcrIE9.2 may be associated with the dissemination of blaKPC in ST15 by repressing CRISPR-Cas activity.

Pneumonia in Children During the 2019 Outbreak in Xiamen, China.

BACKGROUND: To understand the regional epidemiology and clinical characteristics of adenovirus pneumonia in hospitalized children during the 2019 outbreak of respiratory adenoviruses in China. METHODS: We analyzed the epidemiologic trend of adenovirus in children hospitalized for acute lower respiratory tract infections in Xiamen in 2019. Adenovirus was identified using direct fluorescent antibody detection. During the peak seasons of adenovirus epidemic, 170 adenovirus-positive specimens were obtained for molecular typing, and the clinical data were collected. RESULTS: Among the 9890 children hospitalized for acute lower respiratory tract infection, 609 (6.2%) were tested positive for adenovirus. The detection rate of adenovirus was significantly higher in boys than in grils (9.5% vs. 4.6%, P < 0.05). Adenovirus activity increased markedly between April and August with the prevalence of 7.3%-12.4%. During the outbreak season, type 7 accounted for 70.6%, followed by type 3 (28.8%) and type 4 (0.6%). Of the 155 cases of adenovirus pneumonia, the median age was 3.0 years (range: 4 month to 9 years), 153 (98.7%) had fever with a mean fever duration of 9.04 ± 5.52 days, 28 (16.5%) had wheezing, 93 (60%) showed segmental or lobar consolidation with atelectasis and 13 (8.4%) showed pleural effusion. Forty-six (29.6%) cases developed severe pneumonia, 7 (4.1%) required mechanical ventilation and 2 (1.2%) died. Younger age, longer duration of fever and higher fever spike were more frequently seen in severe cases (P < 0.05). Twenty-five (16.2%) had C-reactive protein ≥ 40 mg/L, and 91 (58.7%) had procalcitonin ≥ 0.25 mg/L. CONCLUSIONS: Adenovirus types 7 and 3 caused the outbreak of adenovirus pneumonia in community children during late spring to summer in 2019 in Xiamen. The majority of adenovirus pneumonia resembles bacterial pneumonia. The incidence of severe pneumonia was high when type 7 predominantly prevailed. Adenovirus type 7 was more common in severe cases than in nonsevere cases.

Common issues and improvement solution of vaccine hesitancy in children with underlying neurological conditions: Experience from one National Children's Medical Center in China.

BACKGROUND: Parents and healthcare providers usually defer or avoid immunization for children with neurological conditions. This study was conducted to investigate the common issues of immunization among these special children and the impact of specialists' recommendation on improving immunization practice. METHOD: We included 2,221 children with underlying neurological conditions seeking vaccination consultation at the first Immunization Advisory Clinic in China during 2017-2019. The primary neurological conditions and immunization status were analyzed. All parents were informed to self-report the adverse events following catch-up immunization. For specially concerned children with hereditary disorders, immune-related encephalopathy and epilepsy, we conducted the active follow-up to monitor the compliance with recommendation and the adverse events. RESULT: All counselling children were assessed as not having any contraindication of immunization. A total of 2,019 (90.9%) children with underlying neurological conditions had delayed immunization and 99 (4.5%) had non-immunization. The coverage rate of age-appropriate vaccines was 56.1%. The most concerned vaccines were diphtheria, tetanus and acellular pertussis combined vaccine, diphtheria and tetanus combined vaccine, meningococcal polysaccharide vaccine and Japanese encephalitis vaccine. Resuming immunization was recommended for the 2,048 (92.2%) children. Most of counselling children complied with the specialists' recommendation. Neither progress nor flaring of the neurological medical conditions was reported from parents. CONCLUSION: Vaccine hesitancy was a common issue for Chinese children with all kinds of neurological conditions. Specialized consultation on immunization is helpful to build vaccine confidence for the special children. Immunization for children with underlying neurological conditions is generally safe.

Global fjords as transitory reservoirs of labile organic carbon modulated by organo-mineral interactions.

The global carbon cycle is strongly modulated by organic carbon (OC) sequestration and decomposition. Whereas OC sequestration is relatively well constrained, there are few quantitative estimates of its susceptibility to decomposition. Fjords are hot spots of sedimentation and OC sequestration in marine sediments. Here, we adopt fjords as model systems to investigate the reactivity of sedimentary OC by assessing the distribution of the activation energy required to break OC bonds. Our results reveal that OC in fjord sediments is more thermally labile than that in global sediments, which is governed by its unique provenance and organo-mineral interactions. We estimate that 61 ± 16% of the sedimentary OC in fjords is degradable. Once this OC is remobilized and remineralized during glacial maxima, the resulting metabolic CO2 could counterbalance up to 50 ppm of the atmospheric CO2 decrease during glacial times, making fjords critical actors in dampening glacial-interglacial climate fluctuations through negative carbon cycling loops.

Asp50Glu mutation in MurA results in fosfomycin resistance in Enterococcus faecium.

OBJECTIVES: Enterococcus faecium is one of the important pathogens causing nosocomial infection, which can be resistant to fosfomycin by obtaining the plasmid-encoded fosfomycin resistance genes, and the mutation of MurA protein encoded by chromosome is a newly discovered fosfomycin resistance mechanism in recent years. METHODS: In this study, we found a fosfomycin-resistant clinical isolate of E. faecium Efm_1415 with fosfomycin MIC of 512 mg/L, carrying Asp50Glu mutant of MurA protein, which was never reported before. To study the role and mechanism of this mutant protein in fosfomycin resistance, we used gene cloning, protein expression, and purification, steady-state kinetic, fosfomycin inhibition assay, and next-generation sequencing (NGS) to investigate the functions, characters, and enzymatic kinetic properties of MurA protein. RESULTS: The results revealed that the Asp50Glu MurA can mediate a 4-fold increase in the fosfomycin MIC of the host bacteria. Compared with the wild-type MurA, the affinity of the Asp50Glu MurA to the substrates was increased, and the enzyme activity cannot be inhibited by the concentration of fosfomycin less than 100 mg/L. CONCLUSIONS: The research on the mutant MurA had gained a new understanding of the fosfomycin resistance mechanisms and helped to find new antibiotics with MurA enzyme as the target of action.

Clinical and molecular characterization of the first culture-confirmed pediatric fulminant meningococcemia case caused by a serogroup Y clonal complex 23 strain in China.

Serogroup Y Neisseria meningitidis (NmY) is rare in China, and only serogroup A and C meningococcal polysaccharide vaccines (MPVs) are included in the national vaccination schedule. We describe a case of fulminant meningococcemia caused by NmY, which occurred in a pediatric patient (2 years old) for the first time in China, confirmed by culture. Although the boy was treated in time, the dry gangrene in his toes and fingers left him with severe sequelae. An NmY isolate was cultured from the blood of the patient, and showed decreased susceptibility to penicillin (minimum inhibitory concentration of 0.125 µg/ml), with sequence type (ST) 1655 assigned to clonal complex (cc) 23. Genomic analysis showed it was clustered with isolates from Italy, UK, Finland, and South Africa, sharing designation of Y:P1.5-1,10-1:F4-1:ST-1655(cc23). The emergence of NmY invasive meningococcal disease cases challenges local immunization strategy and warrants wider usage of MPV-ACYW if there is sustained circulation of NmY.

Antibiotic Use Among Hospitalized Children and Neonates in China: Results From Quarterly Point Prevalence Surveys in 2019.

Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions. Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children's hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification. Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2% (n = 2,331) were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections (43.2%, n = 6,379). WHO Watch group antibiotics accounted for 70.4% of prescriptions (n = 12,915). The most prescribed antibiotic ATC classes were third-generation cephalosporins (41.9%, n = 7,679), followed by penicillins/ß-lactamase inhibitors (16.1%, n = 2,962), macrolides (12.1%, n = 2,214) and carbapenems (7.7%, n = 1,331). Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented.

Aetiology of acute diarrhoea in children in Shanghai, 2015-2018.

Diarrhoea remains a major cause of childhood morbidity and mortality worldwide. This study aimed to monitor the aetiology of acute diarrhoea in children in Shanghai. Paediatric outpatients with acute diarrhoea were enrolled in the study from Jan 2015 to Dec 2018. Faecal samples were collected for testing. Enteric bacteria were identified and typed by culture and serotyping, respectively. Enteric viruses were identified by real-time PCR. Enteric pathogens were identified in 1572 (58.4%) of the 2692 enrolled children with acute diarrhoea. Viruses were detected more frequently than bacteria (41.3% versus 25.0%). Nontyphoidal Salmonella spp. (NTS) was the most common (10.3%) bacteria isolated, followed by enteropathogenic Escherichia coli (EPEC) (6.5%), enteroaggregative Escherichia coli (EAEC) (6.2%), Campylobacter spp. (3.6%), enterotoxigenic Escherichia coli (ETEC) (1.1%), Shigella spp. (0.2%), and enterohemorrhagic Escherichia coli (EHEC) (0.1%). Rotavirus was the most common (16.0%) virus detected, followed by norovirus (15.5%), adenovirus (7.2%), sapovirus (3.0%) and astrovirus (2.7%). Rotavirus, norovirus and NTS were the major pathogens responsible for diarrhoea in Shanghainese children. Improving uptake of the rotavirus vaccine and strengthening foodborne-pathogen prevention will aid in reducing the burden of diarrhoeal disease in children in Shanghai.

Comparison of Clinical and Epidemiological Characteristics of Asymptomatic and Symptomatic SARS-CoV-2 Infection in Children.

To understand the epidemiological and clinical features of the symptomatic and asymptomatic pediatric cases of COVID-19, we carried out a prospective study in Shanghai during the period of January 19 to April 30, 2020. A total of 49 children (mean age 11.5 ± 5.12 years) confirmed with SARS-CoV-2 infection were enrolled in the study, including 11 (22.4%) domestic cases and 38 (77.6%) imported cases. Nine (81.8%) local cases and 12 (31.6%) imported cases had a definitive epidemiological exposure. Twenty-eight (57.1%) were symptomatic and 21 (42.9%) were asymptomatic. Neither asymptomatic nor symptomatic cases progressed to severe diseases. The mean duration of viral shedding for SARS-CoV-2 in upper respiratory tract was 14.1 ± 6.4 days in asymptomatic cases and 14.8 ± 8.4 days in symptomatic cases (P > 0.05). Forty-five (91.8%) cases had viral RNA detected in stool. The mean duration of viral shedding in stool was 28.1 ± 13.3 days in asymptomatic cases and 30.8 ± 18.6 days in symptomatic participants (P > 0.05). Children < 7 years shed viral RNA in stool for a longer duration than school-aged children (P < 0.05). Forty-three (87.8%) cases had seropositivity for antibodies against SARS-CoV-2 within 1-3 weeks after confirmation with infection. In conclusion, asymptomatic SARS-CoV-2 infection may be common in children in the community during the COVID-19 pandemic wave. Asymptomatic cases shed viral RNA in a similar pattern as symptomatic cases do. It is of particular concern that asymptomatic individuals are potentially seed transmission of SARS-CoV-2 and pose a challenge to disease control.

Non-polio enterovirus infections in children with central nervous system disorders in Shanghai, 2016-2018: Serotypes and clinical characteristics.

BACKGROUND: Non-polio enrerovirus causes a wide spectrum of neurologic syndromes. The epidemiological and clinical profiles of non-polio enrerovirus-associated central nervous system infections vary by regions and over year. OBJECTIVES: This study aimed to understand the prevalence, serotypes and clinical characteristics of enterovirus-associated aseptic meningitis, encephalitis and meningo-encephalitis in children in Shanghai during 2016-2018. METHODS: We collected the clinical data and the cerebrospinal fluid specimens from the pediatric patients with aseptic meningitis, encephalitis and meningo-encephalitis during 2016-2018. The nested RT-PCR and sequencing were performed to identify enterovirus and serotypes. RESULTS: A total of 424 patients were included in this study and their non-duplicated cerebrospinal fluid specimens were collected during the acute stage of illness. Based on PCR assay, enterovirus was detected in 272 (64.15 %) patients, of whom, the ratio of male to female subjects was 1.99, and the mean age was 5.71 ± 3.55 years (range: 0.03-16 years). There were 17 serotypes identified. Echovirus 30 (24.63 %), Coxsackievirus A10 (20.96 %), Coxsackievirus A6 (18.01 %) accounted for 63.6 %, followed by Coxsackievirus B5 (7.72 %), Echovirus 6 (5.88 %), and other serotypes (22.8 %). Of the 10 (3.68 %) critically severe patients, all had refractory seizure, 8 required mechanical ventilation, 7 survivors had recurrent attacks of epilepsy and 3 abandoned treatment; Coxsackievirus A10, Echovirus 9, Coxsackievirus A2, Coxsackievirus A6 and Echovirus 6 were identified. CONCLUSIONS: Non-polio enterovirus is the major pathogen causing aseptic meningitis, encephalitis and meningo-encephalitis in Chinese children and can cause life-threatening encephalitis and severe sequelae.

Pediatric Antibiotic Prescribing in China According to the 2019 World Health Organization Access, Watch, and Reserve (AWaRe) Antibiotic Categories.

OBJECTIVES: To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas. STUDY DESIGN: Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification. RESULTS: A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%). CONCLUSIONS: Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics.