Carbapenem-resistant organisms (CROs) pose a severe health threat to pediatric patients. We aimed to investigate the epidemiology, clinical infection, and molecular profiles of CROs in Chinese children from 2016 to 2025. We retrospectively analyzed 3655 non-duplicate CRO strains isolated from Children’s Hospital of Fudan University between 2016 and 2025, and further selected 499 carbapenem-resistant Enterobacterales (CRE) strains and 315 single or multiple CRO infection cases to investigate the characteristics of different CROs. The predominant CRO pathogens included carbapenem-resistant A. baumannii (CRAB, 28.5

OBJECTIVES:A global resurgence of pertussis has followed the COVID-19 pandemic, yet the underlying drivers remain unclear. We investigated the contribution of Bordetella pertussis genomic evolution to the post-pandemic resurgence. METHODS:We analyzed 8117 B. pertussis genomes from 35 countries, including 249 newly sequenced isolates collected from six regions in China. Temporal dynamics of genotypes, antigenic profiles, and macrolide resistance were examined before, during, and after the pandemic. RESULTS:Shared post-pandemic evolutionary patterns were identified across global B. pertussis populations. These included the emergence of macrolide-resistant strains in France, the United States, and Australia, and their dominance in eastern China, driven by the expansion of the MR-MT28 sublineage (ptxP3/fim3-1/prn150 or PRN-deficient). Parallel antigenic shifts were observed, with declining PRN-deficient strains accompanied by increasing prn2 allele frequencies in multiple regions. Region-specific dynamics were also evident. In China, the post-pandemic resurgence was characterized by near-complete replacement of circulating strains by the MR-MT28 sublineage. In contrast, the resurgence in Europe and the United States largely reflected the persistence and expansion of locally established lineages. Expanded sampling further revealed that MR-MT28 sublineage is no longer genetically homogeneous, having diversified into multiple phylogenetic groups, with most isolates detected outside China (72%, 8/11) being PRN-deficient. CONCLUSIONS:This unified global genomic analysis demonstrates both shared and region-specific post-pandemic shifts in B. pertussis populations. The dominance of the MR-MT28 sublineage in China, together with its international dissemination and ongoing diversification, represents a growing public health concern and underscores the need for coordinated global genomic surveillance.

Background:The changes in the antibiotic resistance patterns of Helicobacter pylori (H. pylori) are critical for guiding clinical eradication therapy. However, data on antibiotic resistance in H. pylori strains isolated from children in Shanghai have been unavailable for the past three years. Methods:676 H. pylori strains isolated from children and relevant clinical information was collected. Antibiotic susceptibility of metronidazole, clarithromycin, levofloxacin and amoxicillin was tested by E-test, resistance gene mutations were detected via PCR and sequencing. Results:Among 676 H. pylori isolates, total resistance rates to metronidazole, clarithromycin, levofloxacin and amoxicillin were 61.5%, 39.1%, 18.2% and 0.3%, respectively. Resistance rates to metronidazole, clarithromycin increased significantly from 2023 to 2025, with increased dual and hetero-resistance. Higher rates of resistance to metronidazole and levofloxacin were observed in the 7-12 year-old group than other two age groups. A2143G in 23S rRNA (98.7%) and N87K in gyrA (61.0%) were the main mutations for clarithromycin and levofloxacin resistance. Conclusion:Over the past three years, a substantial increase in antibiotic resistance toward metronidazole and clarithromycin is observed in H. pylori isolated from children in Shanghai, China.

OBJECTIVE:Carbapenem-resistant Klebsiella pneumoniae (CRKP) central nervous system (CNS) infections are difficult to treat in children because effective and safe therapeutic options are limited. We report a paediatric case of CRKP meningitis successfully treated with ceftazidime-avibactam (CZA) combination with intraventricular polymyxin B (PMB). METHODS:A 9-y-old child with severe traumatic brain injury and multiple prior neurosurgical procedures developed CRKP meningitis. After pathogen identification, antimicrobial therapy was switched to CZA plus intraventricular PMB, and the ventriculoperitoneal shunt was externalized. Clinical outcomes, cerebrospinal fluid (CSF) parameters, microbiological clearance, and plasma and CSF concentration of CZA were monitored during treatment. RESULTS:After CRKP was identified, therapy was adjusted to CZA (62.5 mg/kg every 8 h, administered as a 2-h infusion) plus intraventricular PMB based on susceptibility results. Fever resolved within 3 d of CZA initiation. CSF cultures became negative, and CSF parameters gradually normalized. Neurological status improved, and the patient was transferred to a rehabilitation facility. Pharmacokinetic analysis showed blood-brain barrier penetration rates of 19.4% for ceftazidime and 29.9% for avibactam. CONCLUSIONS:This report adds to the limited pharmacokinetic/pharmacodynamic (PK/PD) evidence for ceftazidime-avibactam in paediatric CNS infections. It also supports the potential role of ceftazidime-avibactam combined with intraventricular polymyxin B as a therapeutic option for CRKP meningitis in children. Further studies are needed to optimize dosing strategies and evaluate long-term safety in the paediatric population.

Background: Rates of carbapenem-resistant organism (CRO) colonization and infection are rising in pediatric intensive care units (PICUs), mainly due to underlying comorbidities, frequent invasive procedures, prolonged hospitalization, and extensive use of broad-spectrum antibiotics. Colonized patients can act as reservoirs for nosocomial transmission of drug-resistant bacteria, posing a serious threat to other children and healthcare workers. Prevention and control of CRO are therefore of urgent clinical importance. Methods: Based on active screening measures, we analyzed risk factors for intestinal CRO colonization and subsequent nosocomial infection in critically ill children. Pulsed-field gel electrophoresis (PFGE) was used to determine molecular homology between colonizing and infecting strains isolated from the same patient. Results: A total of 1069 children were admitted to our PICU between January 2021 and September 2022. Seventy-seven cases of intestinal CRO colonization were detected, with a colonization rate of 7.2%. Of these colonized children, 15 developed subsequent CRO infection, and PFGE confirmed that the infecting strains were homologous to the colonizing ones. Independent risk factors for CRO colonization included underlying neuromuscular disease (OR 7.048, 95% CI 3.003-16.545, P<0.001) and longer hospital stay (OR 1.063, 95% CI 1.034-1.092, P<0.001). Among colonized children, independent risk factors for subsequent nosocomial infection were carbapenem exposure (OR 4.041, 95% CI 1.310-12.470, P=0.014), absence of contact isolation (OR 0.033, 95% CI 0.002-0.496, P=0.010), and longer hospital stay (OR 1.083, 95% CI 1.002-1.170, P=0.045). Conclusion: Intestinal CRO colonization significantly increases the risk of subsequent homologous nosocomial infection in PICU children. Rational carbapenem use,aprompt contact isolation following colonization and shorten hospitalization time are crucial strategies to reduce CRO-related nosocomial infections.

Background Identifying the pathogens responsible for urinary tract infections (UTIs) using urine culture methods is time-consuming, and delayed diagnosis significantly impacts patient outcomes.Methods We developed a novel platform that combines PCR amplification products with quantum dot fluorescence for hybridization-Polymerase Chain Reaction Combined with Quantum Dot Fluorescence Analysis (PCRQDFA), enabling rapid and efficient detection of pathogenic bacteria in urine. To evaluate the performance of this technique, 294 urine samples from children with UTI were collected and tested using PCR-QDFA and traditional culture methods.Results Compared to culture, the consistency rate of PCR-QDFA was 86.73%, with a sensitivity of 86.98% and a specificity of 86.4%. For common pathogens such as Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Proteus mirabilis, and Enterobacter cloacae, the consistency rates exceeded 95%.Conclusion The PCR-QDFA assay has proven to be a reliable tool for the rapid diagnosis of urinary pathogens in children with suspected urinary tract infections.

Candidemia is life-threatening in children. Limited epidemiological and antifungal resistance data for children necessitate national surveillance. This multicenter retrospective study (2016-2024) analyzed 527 pediatric candidemia cases from 13 children's hospitals via the Infectious Disease Surveillance of Pediatrics (ISPED) network. Candida species caused 96.0% (527/549) of fungemia cases. Neonates and infants comprised 51.6% of cases (24.5% neonates and 27.1% infants). Non-albicans Candida species (NACs) dominated (74.0%), with the prevalence of Candida parapsilosis increasing from 21.2% in 2019 to 51.9% in 2024 (Z = 3.11, P = 0.002), while the prevalence of C. albicans decreased from 38.9% to 15.6% during the same period (Z = -2.25, P = 0.024). Azole susceptibility of NACs decreased significantly: C. parapsilosis fluconazole susceptibility decreased from 93.5% (2016-2018) to 63.6% (2022-2024) (P < 0.001), whereas voriconazole (79.5%-93.3%, P = 0.078) and itraconazole (80.0%-97.4%, P = 0.369) susceptibility remained high. Candida tropicalis showed low azole susceptibility, with significant decreases in susceptibility to fluconazole (61.5% in 2016-2018 to 35.0% in 2022-2024) and voriconazole (61.5% in 2016-2018 to 20.0% in 2022-2024; P < 0.001 for all). The susceptibility of wild-type Candida guilliermondii decreased toward fluconazole (100.0% in 2016-2018 and 2019-2021 to 38.9% in 2022-2024), voriconazole (100.0% in 2016-2018 and 2019-2021 to 27.8% in 2022-2024), and itraconazole (100.0% in 2016-2018 and 2019-2021 to 22.2% in 2022-2024) (P < 0.001 for all). All Candida species showed high susceptibility to amphotericin B and echinocandins (99.0% and 95.9%, respectively). Overall, there was a notable shift toward NACs, especially C. parapsilosis, C. tropicalis, and C. guilliermondii, accompanied by declining susceptibility to azoles (particularly in C. tropicalis and C. guilliermondii), which underscores the urgent need for enhanced antifungal stewardship and continuous resistance monitoring.

The optimal timing of the first dressing change after central venous catheter (CVC) insertion remains unclear. To test whether a first dressing change at seven days is non-inferior to an additional change at 24 h, we conducted a multicenter randomized controlled non-inferiority trial in four Chinese pediatric ICUs (April 2021-December 2022). A total of 280 patients aged 1 month to 18 years with a newly inserted CVC were randomly assigned to the control group (dressing change at 24 h, then every seven days) or the experimental group (first dressing change at seven days). The primary outcome was skin bacterial colonization under the transparent dressing, assessed at day 7 (experimental) and day 8 (control). In the intention-to-treat population, colonization occurred in 25.6% of experimental patients and 26.8% of controls (difference, - 1.1%; 95% CI, - 13.0% to 10.7%), with the upper CI limit below the prespecified noninferiority margin of 20%. Catheter related bloodstream infection(CRBSI) rates were 1.42 vs. 2.72 per 1,000 catheter days (no significant difference). Only one skin injury occurred. Delaying the first dressing change to seven days did not increase skin bacterial colonization and showed no significant difference in CRBSI, suggesting that this practice is safe with respect to colonization risk. Definitive conclusions regarding infection safety require a larger trial.

Objective: The primary objective of this study was to examine the epidemiology and antibiotic resistance of food-borne diseases in pediatric populations in Shanghai from 2021 to 2024. Methods: Data were collected from patients presenting with suspected food-borne illnesses at the intestinal clinic of the Children's Hospital of Fudan University during the period from July 1, 2021 to June 30, 2024. Fresh stool samples from all enrolled patients were analyzed for six pathogens: Salmonella, Vibrio parahaemolyticus, Diarrheagenic Escherichia coli, Campylobacter, Shigella, and Norovirus. Detection of Salmonella, Shigella, Diarrheagenic Escherichia coli and Norovirus was performed using polymerase chain reaction (PCR) methods, while culture assays were utilized for Salmonella, Shigella, Vibrio parahaemolyticus, and Campylobacter. Antimicrobial susceptibility testing of the isolated strains (102 Salmonella and 90 Campylobacter isolates) was performed in accordance with CLSI M100 and M45 guidelines, 2024. Results: A total number of 795 cases were included in the study, revealing an overall positivity rate of 68.3% (543/795). This positivity rate indicates that at least one of the six pathogens tested was positive. The predominant pathogen identified was Diarrheagenic Escherichia coli, which accounted for 49.2% (391/795) of cases. Co-infections were identified in 20.0% (159/795) of the samples analyzed. Salmonella resistance rates were high, at 74.5% for ampicillin and 24.5% for multi-drug resistance. Campylobacter exhibited over 80% resistance to ciprofloxacin and tetracycline; 18.9% of isolates were resistant to all three tested antibiotics. Conclusion: Food-borne pathogens are widely prevalent among children with suspected food-borne illnesses in Shanghai, and the high levels of antibiotic resistance observed in Salmonella and Campylobacter highlight a critical public health concern. These findings underscore the necessity for strengthened surveillance of pediatric food-borne diseases, rational clinical use of antibiotics, and implementation of targeted preventive strategies to reduce the burden of drug-resistant infections in this vulnerable population.

Objective Salmonella and its increasing antimicrobial resistance (AMR) threaten public health. This study analyzed the epidemiology and AMR profiles of pediatric Salmonella in China to support rational antibiotic use. Method A multicenter retrospective study included 17540 Salmonella isolates from ISPED (2017–2024). Antimicrobial susceptibility was tested by disk diffusion and MIC, and analyzed with WHONET. Results Most isolates were from feces, peaking in children aged 1–3 years and during June–October. S. typhimurium and S. enteritidis were predominant. High resistance was observed to ampicillin (77.8%), ampicillin/sulbactam (39.3%), and trimethoprim/sulfamethoxazole (39.3%), while levofloxacin remained highly effective. Resistance differed by serotype, sample type and region, with S. enteritidis showing rising resistance to fluoroquinolones and cephalosporins. Conclusion Treatment should be individualized according to Salmonella serotype, regional epidemiological characteristics and antimicrobial susceptibility. Continuous national antimicrobial resistance surveillance is vital to improve antibiotic stewardship and public health interventions. Based on the multicenter ISPED program, this study clarified the epidemiological features and antimicrobial resistance of Salmonella isolates among Chinese children from 2017 to 2024. The findings support targeted public health planning, rational antibiotic use in pediatrics, strengthened Salmonella surveillance, and policy development for food safety and childhood infectious disease prevention.

Building a neuromorphic vision sensor capable of signal processing and spike generation is essential for developing hardware tailored to brain-inspired spiking neural networks. A critical challenge, however, is the constrained adaptive sensitivity when dealing with expanding ranges of light intensity. Here we show a neuromorphic vision sensor built on a one-transistor-one-memristor pixel structure, attaining high encoding-sensitivity over a broad intensity range by fusing complementary superlinear and sublinear encoding. Specifically, the superlinear intensity-to-spike firing is based on the plasmonic volatile Ag/hBN/Au memristor, which has the high time-to-first-spike (TTFS)- and rate- encoding sensitivity in high-brightness. And the sublinear firing behavior is based on the MoS2 synaptic photodetector and volatile Ag/hBN/Au memristor neuron, which has the high TTFS- and rate- encoding sensitivity in dim light. When deployed in polar environments (intense brightness to darkness), the complementary vision sensor achieves high-quality imaging, segmenting ice/land regions and predicting thickness-showcasing its robustness under challenging conditions.

Abstract This study analysed bacterial infections and antimicrobial resistance (AMR) profiles of the top five pathogens in adult intensive care units (ICUs) and paediatric ICUs (PICUs) in China from 2017 to 2022, aiming to inform AMR surveillance and treatment guidelines. Antimicrobial susceptibility was assessed via automated systems or the Kirby-Bauer method, interpreted per Clinical and Laboratory Standards Institute breakpoints, and analysed using WHONET 5.6. 22,278 and 152,117 unduplicated clinical bacterial isolates were collected from 17 PICUs and 44 adult ICUs. The rate of Gram-negative bacteria was higher in adult ICUs than in PICUs (78.5% vs. 62.6%, P < 0.001). The top five clinical isolates in both departments were Staphylococcus aureus , Acinetobacter baumannii , Klebsiella pneumoniae , Pseudomonas aeruginosa , and Escherichia coli. From 2017 to 2022, E. coli , K. pneumoniae , and P. aeruginosa generally showed decreased resistance to most antimicrobial agents in adult ICUs, but increased resistance in PICUs. Resistance of A. baumannii and S. aureus to most antimicrobial agents decreased in both PICUs and adult ICUs. The resistance proportions of E. coli to ceftazidime-avibactam, ceftriaxone, and imipenem; K. pneumoniae to ceftazidime-avibactam and ceftriaxone; and P. aeruginosa to amikacin were higher in PICUs than in ICUs. For other detected antibacterial agents, all five pathogens showed higher resistance in adult ICUs than in PICUs ( P < 0.05). These data reveal a severe AMR burden in ICUs, with notable differences between PICUs and adult ICUs. Enhanced ICU-specific AMR surveillance, rigorous infection control, and optimised antibiotic stewardship are imperative to counter multidrug-resistant pathogens. Although escalating resistance trends remain a major concern in PICUs, significant reductions in resistance for several pathogens in adult ICUs likely reflect the impact of strengthened antimicrobial stewardship and infection control programs in China.

Pertussis resurgence following the COVID-19 pandemic remains poorly understood. Here, we integrate global surveillance data with 8,117 Bordetella pertussis genomes from 35 countries to investigate the role of pathogen evolution. We identify substantial shifts in B. pertussis populations in China and Australia, alongside marked changes in multiple European countries. In China, resurgence is driven by the rapid expansion of a single macrolide-resistant clone, MR-MT28. Elsewhere, resurgence involves diverse, pre-pandemic polyphyletic strains. Australia and Europe show convergent antigenic changes, including a decline in pertactin-deficient strains, a rise in prn2 alleles, and rising macrolide resistance. Notably, we detect post-pandemic international dissemination of MR-MT28 across four continents, with non-Chinese isolates belonging predominantly to a pertactin-deficient subclone. These findings reveal convergent and region-specific strain replacement, antigenic evolution and macrolide resistance, highlighting the key role of adaptive evolution in the global pertussis resurgence. The emergence and global spread of MR-MT28 underscore the urgent need for coordinated global surveillance. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by grants from National Key Research and Development Program of China (2022YFC2304700), National Natural Science Foundation of China (82202567, 32270003), Youth Innovation Promotion Association, Chinese Academy of Sciences (2022278), and Shanghai Rising-Star Program (23QA1410500), Zhejiang Provincial Science and Technology Program for Disease Prevention and Control (2025JK139), Sigrid Juselius Foundation (240045) and Tampere Tuberculosis Foundation (26006205). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The isolates used in this study had been fully de-identified prior to use and cannot be linked back to the patients. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors All data produced in the present work are contained in the manuscript Accession numbers for the publicly available genome sequences and associated metadata can be found in appendix and Zenodo (DOI:10.5281/zenodo.15900428). Newly sequenced genomes in this study are available from the National Centre for Biotechnology Information database under BioProject PRJNA1288341.

OBJECTIVE:This study aimed to analyze the profiles and evolution of Staphylococcus aureus in the pediatric intensive care units (PICUs) of 17 hospitals in China from 2016 to 2022. METHODS:Susceptibility testing was performed to bacterial strains with a uniform monitoring protocol, which was provided by the US Clinical and Laboratory Standards Institute (CLSI) and used by the China Antimicrobial Surveillance Network (CHINET). The results were interpreted in accordance with the performance standards for antimicrobial susceptibility testing issued by the US Clinical and Laboratory Standards Institute. RESULTS:Twenty-six thousand six hundred thirteen bacterial strains were isolated from 17 PICUs in China from 2016 to 2022, 3,147 of which were Staphylococcus aureus, ranking second among etiological agents of infections from PICUs. In 2022, Staphylococcus aureus had the highest detection rate, being 36.19%. And in 2021, MRSA had the highest detection rate, being 10.35% in Staphylococcus aureus. There were statistically significant differences in the annual detection rate of gram-positive bacteria, Staphylococcus aureus and MRSA between the years from 2016 to 2022 (P < 0.05). More males were found with Staphylococcus aureus or methicillin-resistant Staphylococcus aureus, but there were no statistical differences in gender distribution between any two years (P < 0.05). The top 3 highest detection rate of Staphylococcus aureus in age groups were infants (1244, 39.7%), toddlers (741, 23.7%), and children at school age and older (731, 23.4%). For MRSA, The top 3 in age groups were infants (91, 38.9%), children at school age and older (87, 29.1%), and toddlers (48, 20.5%). The detection rate of Staphylococcus aureus was statistically different in the distribution of age stratification (P < 0.05). There was no statistically significant difference in these two aspects of MRSA (P > 0.05). The top 3 highest detection rate of Staphylococcus aureus in infected sites were the lower respiratory tract (2,552, 81.7%), bloodstream (217, 6.5%), and skin wounds (110, 3.9%). For MRSA, The top 3 in infected sites were the lower respiratory tract (156, 77.9%), skin wounds (47, 8.8%), and bloodstream (15, 6.6%). The detection rate of Staphylococcus aureus and MRSA was statistically different in the distribution of infected sites (P < 0.05). All the strains of Staphylococcus aureus were sensitive to tigecycline, nitrofurantoin, vancomycin, and linezolid. The resistant rate of Staphylococcus aureus, to penicillin G was as high as 87.5% at least, to erythromycin was as high as 51.8% at least, to benzocillin was as high as 38.0% at least, to cefoxitin was as high as 35.5% at least, and to clindamycin was as high as 32.7% at least. All the strains of MRSA were sensitive to vancomycin, linezolid, quinupristin/dalfopristin, and tigecycline. Of these 234 strains of MRSA, 179 (76.5%) were resistant to erythromycin, 116 (49.6%) to clindamycin, 39 (16.7%) to tetracycline, 29 (12.4%) to levofloxacin, 27 (11.5%) to ciprofloxacin, 27 (11.5%) to moxifloxacin, 14 (6.0%) to TMP-SMX, eight (3.4%) to rifampicin, and six (2.6%) to gentamicin. CONCLUSIONS:Staphylococcus aureus is the most common gram-positive bacterium in PICUs. Infants are most likely to be infected by Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. And the lower respiratory tract is the most common infected site of Staphylococcus aureus. Staphylococcus aureus has a high resistant rates to commonly used antimicriobials in pediatrics, but no strains resistant to vancomycin and/or linezolid were found. When considering Staphylococcus aureus infection clinically, it is necessary to select antimicrobials reasonably based on the patient's age, infected site and local epidemiological characteristics.

Objective:This study investigated the long-term trends in the distribution and antibiograms of ESKAPEEc pathogens in neonatal and pediatric bloodstream infections (BSIs), shifts in minimum inhibitory concentration (MIC) of vancomycin and linezolid in Staphylococcus aureus, along with the changing patterns of antimicrobial resistance phenotypes over time in China. This work provides a reference for the prevention and treatment of pediatric BSIs. Methods:A multicenter retrospective surveillance study was carried out from 2016 to 2023 at 12 tertiary pediatric hospitals across nine provinces and autonomous regions in China. The collected data were analyzed using GraphPad Prism 8 and WHONET 5.6. Temporal variations and linear trends were evaluated using chi-square or Fisher's exact tests. Results:A total of 10,051 ESKAPEEc strains accounted for 22.5% (10,051/44,675) of all BSIs, with 32.3% from neonatal BSIs and 67.7% from pediatric BSIs. The detection rate of ESKAPEEc pathogens increased for post the coronavirus disease 2019 (COVID-19) compared to the pre-COVID-19. Carbapenem resistance levels were 5.5% in Escherichia coli, 28.0% in Klebsiella pneumoniae, 16.0% in Enterobacter cloacae, 12.5% in Pseudomonas aeruginosa and 38.5% in Acinetobacter baumannii. Both Staphylococcus aureus and Enterococcus faecium remained fully susceptible to vancomycin and linezolid. Between 2016-2019 and 2020-2023, resistance to ceftazidime and gentamicin decreased in Escherichia coli and Klebsiella pneumoniae while resistance to imipenem and meropenem increased. Acinetobacter baumannii exhibited reduced resistance to most antibiotics except cefotaxime, levofloxacin and amikacin. Staphylococcus aureus displayed a declining resistance to macrolides and aminoglycosides but increasing resistance to fluoroquinolones, whereas Enterococcus faecium exhibited reduced resistance to all tested antibiotics. Compared to neonatal BSIs, Klebsiella pneumoniae from pediatric BSIs exhibited lower resistance to all β-lactams especially carbapenems (32.3% vs. 15.0%) while Acinetobacter baumannii displayed higher resistance to all tested agents. Methicillin-susceptible Staphylococcus aureus (MSSA) strains had lower vancomycin MIC ≥2 μg/mL levels compared to methicillin-resistant Staphylococcus aureus (MRSA) strains. Significant temporal differences were observed in MRSA isolates with linezolid MIC ≥2 μg/mL but not in MSSA isolates. The MIC50 of vancomycin in MRSA strains was either equal to or higher than in MSSA strains from 2016 to 2022. The most frequently detected bacteria in carbapenem resistance, extended-spectrum cephalosporin resistance, fluoroquinolone resistance and aminoglycoside resistance were Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli and Acinetobacter baumannii respectively. Conclusions:The incidence of ESKAPEEc in BSIs has increased, and the rising resistance to imipenem and meropenem in Escherichia coli and Klebsiella pneumoniae underscores the need for continued surveillance. Carbapenems remain effective against Gram-negative ESKAPEEc, while vancomycin and linezolid remain effective against Gram-positive ESKAPEEc. Age-stratified strategies are essential to manage carbapenem-resistant Klebsiella pneumoniae in neonatal BSIs and carbapenem-resistant Acinetobacter baumannii in pediatric BSIs. The MIC values for vancomycin in MRSA strains remained stable over time, whereas a decreasing susceptibility trend to vancomycin in MSSA strains and linezolid MIC shifts were not observed. Our findings are expected to provide to treatment of bloodstream infections in children and evidence on best practices and resource sharing for policy consideration to healthcare providers at the local and international levels.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a serious threat to global public health. Hypervirulent CRKP (Hv-CRKP) can cause life-threatening infections, with significantly higher virulence and mortality compared to classical CRKP. CRKP strains were isolated from hospitalized patients in Shandong Province, China, 2018–2023. We performed whole-genome sequencing and bioinformatic analyses to determine the multilocus sequence typing (MLST), capsular typing, antimicrobial resistance genes, virulence factors, and plasmid incompatibility (Inc) typing of these strains. 81 CRKP strains were collected, with the major carbapenemase genes were blaNDM−1 (49.4

A 9-month-old ICU patient with persistent carbapenem-resistant Acinetobacter baumannii pneumonia developed a secondary infection of carbapenem-resistant Klebsiella pneumoniae. A customized, preoptimized phage cocktail was administered twice daily for 3 consecutive days, resulting in eradication of the pathogens and reduction in their abundance in the lung and gut microbiota.

Bacterial infections, especially multidrug-resistant Gram-negative bacterial infections, pose a great threat to patients with inborn errors of immunity (IEIs). This study investigates the molecular and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CR-AB), carbapenem-resistant Escherichia coli (CR-ECO), and carbapenem-resistant Enterobacter cloacae (CR-ECL) strains from patients with IEI. Strains from IEI and non-IEI groups underwent antimicrobial susceptibility testing and whole-genome sequencing (NovaSeq 6000 PE150), with statistical analysis of differences. A total of 24 CR-AB, 17 CR-ECO, and 16 CR-ECL strains were included. Most CR-AB strains in the IEI group belonged to ST2 (81.8%), all harbored blaOXA-23, followed by ST109 (blaOXA-58, 9.1%) and ST70 (blaNDM-1, 9.1%), whereas all CR-ABs in the non-IEI group were ST2 with blaOXA-23. CR-ECL strains from the IEI group harbored blaKPC-2 (14.3%) and blaVIM-1 (14.3%), in contrast to the non-IEI group. Compared to the non-IEI group, strains in the IEI group exhibited lower carriage of immune modulation genes in CR-AB (18.2%-45.5% vs. 40.0%-80.0%), reduced carriage of adherence genes (50.0%-62.5% vs. 88.9%-100.0%) and nutritional/metabolic factor genes (25.0% vs. 55.6%) in CR-ECO, and lower carriage of nutritional/metabolic factor genes (28.6% vs. 50.0%) in CR-ECL. No statistically significant differences were observed between the groups, except for the fimA gene in CR-ECO (P < 0.05). The distinct molecular characteristics and reduced virulence gene carriage were observed in CR-AB, CR-ECO, and CR-ECL isolates from patients with IEI, with greater carbapenemase gene diversity in CR-AB and CR-ECL. These findings emphasize the need for enhanced surveillance and tailored antimicrobial strategies in IEI populations. IMPORTANCE:Bacterial infection, especially drug-resistant bacterial infection, poses a great risk to patients with IEIs. Antimicrobial resistance, particularly in pediatric patients, is a growing global health threat. Bacteria undergo a series of adaptive changes in response to pressures from the host. Patients with IEI provide a unique immune environment that may profoundly influence the molecular characteristics of bacterial pathogens. However, little is known about the molecular and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CR-AB), Escherichia coli (CR-ECO), and Enterobacter cloacae (CR-ECL) isolated from patients with IEI. This study, the first of its kind, shows that CR-AB, CR-ECO, and CR-ECL from patients with IEI have distinct molecular profiles, including reduced virulence gene carriage and more diverse carbapenemase genes. It highlights the role of host immune status in shaping pathogen evolution and resistance, emphasizing the importance of monitoring the adaptive variation of these bacteria in patients with IEI.

PURPOSE:This study aimed to investigate the spectrum of bacterial infections in children with inborn error of immunity (IEIs). METHODS:Pediatric patients with IEIs and positive for bacteria considered to be pathogenic were included in this retrospective study. RESULTS:In this study, 1811 medical records of IEI inpatients were reviewed, and 243 IEI patients with 290 hospitalizations were enrolled. A total of 361 strains were detected, of which, 83 (22.99%) were gram-positive bacteria, and 278 (77.01%) were gram-negative bacteria. The main bacteria isolated from different IEI classifications were different. Patients with combined immunodeficiencies were more likely to have Klebsiella pneumoniae (12.68%) and Pseudomonas aeruginosa (12.68%) isolated. Patients with predominant antibody deficiencies were more prone to the isolation of Haemophilus influenzae (31.82%) and Moraxella catarrhalis (13.64%). Patients with congenital defects of phagocytes were more frequently associated with the isolation of K. pneumoniae (16.84%) and Escherichia coli (11.58%). Patients with different classifications of IEI were susceptible to specific bacteria. Salmonella was often isolated from patients with defects in intrinsic and innate immunity (4.23%), and Staphylococcus aureus was often isolated from patients with combined immunodeficiencies with syndromic features (5.52%). The percentages of methicillin-resistant S. aureus, carbapenem-resistant E. coli, K. pneumoniae, P. aeruginosa, and Acinetobacter baumannii in IEI patients were55.57%, 38.10%, 25.71%, 25.81%, and 70.59%, respectively, and these values were greater than those in non-IEI patients. CONCLUSION:Children with IEIs exhibit a unique spectrum of bacterial infections. Bacteria isolated from children with IEIs have high antimicrobial resistance.

Background: The upsurge of pertussis post-COVID-19 and expansion of macrolide-resistant Bordetella pertussis (MRBP) pose significant public health challenges worldwide. China has experienced notable pertussis upsurge post-COVID-19, alongside an age shift to older children, vaccine escape and a notable rise in MRBP prevalence. We describe the genomic epidemiological investigation of these events. Method: We did a retrospective, population-based study using culture-positive B. pertussis from Children's Hospital of Fudan University (CHFU), the exclusive referral hospital for childhood notifiable infectious diseases, in Shanghai, China between June 2016 and March 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic proflie, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. Findings: Coincident with national situtation, pertussis cases upsurged post-COVID-19 in Shanghai. At CHFU, the number of confirmed cases (n=349) in the first three months of 2024 exceeded the total case of previously years (n≤177). Post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to widespread infection among older children (infant: 16%, 132/844), with vaccinated individuals surging from 31% (107/340) to 88% (664/756); MRBP prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-linage, macrolide-resistant novel clone with MLVA type 28, MR-MT28, uniquely capable of causing substantial infections among older children and vaccinated individuals, temporally strongly associated with the pertussis upsurge and epidemiological transition. MR-MT28 exhibited increased expression of antigen genes including pertussis toxin genes, along with high incidence of abnormal C-reactive protein, but associated with siginicantly milder clinical symtoms (e.g. wheezing, facial blushing, p<0.01), higher proportion of normal chest computed tomography (p<0.05) and lower hospitalization rate (p<0.01). Phylogenomic clustering analysis revealed a higher proportion of MR-MT28 strains grouping into clusters representing putative transmission. We reconstructed the evolutionary history of MR-MT28, and showed that it most likely originated in China around 2016 (95% highest probability density: 2013-2017) after acquring several mutations, including a novel antigen allele prn150 and 23S rRNA A2047G mutation. Approximately one quarter (26%, 50/195) of MR-MT28 has evolved into predicted PRN-deficient strains. MR-MT28 has been identified in four regions (Anhui, Shanghai, Beijing and Guangdong) of China and continuously detected in Shanghai and Beijing, suggesting domestic spread and colonization. Interpretation: We identified a ptxP3-linage, macrolide-resistant novel clone, MR-MT28, and provide evidence that pathogen evolution is more likely the primary factor driving pertussis upsurge, age shift and vaccine escape. MR-MT28 potentially poses a high global spread risk and warrants global surveillance. Macrolides may no longer be suitable as first-line drugs for pertussis treatment in China.