Mingming Zhou

This study aimed to characterize the species distribution, sequence types, and antimicrobial resistance mechanisms of carbapenem-resistant organisms (CROs) in pediatric patients with hematological malignancies, and to clarify the genomic relationship between clinical infectious CROs and intestinal colonizing CROs. Non-duplicate infectious CRO strains and paired intestinal colonizing CROs were collected from 2020 to 2024. Whole-genome sequencing and bioinformatics analyses were performed to identify bacterial species, multilocus sequence types, resistance genes, mobile genetic elements, and genomic relatedness. Seven CRO species were identified, dominated by Pseudomonas aeruginosa , Klebsiella pneumoniae , and Enterobacter hormaechei . A total of 34 carbapenem resistance-associated genes were detected, with efflux pump overexpression and antibiotic inactivation as the main mechanisms. Three patients carried both infectious and intestinal CROs. Two pairs showed nearly identical genomes (average nucleotide identity >99.99%), confirming infections originated from intestinal colonization. One pair belonged to different species but shared an identical KPC-2 gene located on the same Tn 7247 -like transposon, indicating potential horizontal gene transfer. Diverse CROs and corresponding resistance mechanisms are prevalent in pediatric patients with hematological malignancies. This study identifies the dominant CRO species and key resistance mechanisms in this high-risk population, supporting the gastrointestinal tract as a potential reservoir for CROs, and indicating the likelihood of horizontal transmission of carbapenemase genes. These findings underscore the necessity of intensive surveillance and strict infection control measures to curb the dissemination of CROs in vulnerable pediatric populations. IMPORTANCE: Carbapenem-resistant organisms (CROs) cause life-threatening infections in pediatric patients with hematological malignancies, who are highly vulnerable due to chemotherapy-induced immunosuppression. This study characterized CRO species, resistance mechanisms, and genomic links between infectious and intestinal colonizing strains in this population. We confirmed that intestinal colonization is an important source of subsequent CRO infections and identified interspecies horizontal transfer of the carbapenemase gene KPC-2 via a Tn 7247 -like transposon. These findings highlight the critical need for enhanced intestinal CRO screening and strict infection control measures to protect this vulnerable pediatric group.

Ceftriaxone (CRO) is a first-line antibiotic for pediatric nontyphoidal Salmonella (NTS) infections, but rising resistance threatens public health. Conventional antimicrobial susceptibility testing remains time-consuming, delaying treatment. Although MALDI-TOF MS enables rapid microbial identification, it lacks inherent resistance detection. This study integrates MALDI-TOF MS with machine learning to predict CRO resistance in NTS. Using 472 isolates (1,414 spectra) from three medical centers, we developed and validated a model based on the Light Gradient Boosting Machine (LGB) algorithm. With only seven features, LGB achieved AUCs of 0.94 (training), 0.88 (internal validation), 0.79 (external validation 1), and 0.80 (external validation 2). We further deployed the model as an interactive Streamlit web interface to demonstrate its potential usability and facilitate future laboratory evaluation. This approach provides a proof-of-concept framework for rapid preliminary prediction of ceftriaxone resistance in NTS using routinely generated MALDI-TOF MS spectra. However, further large-scale, prospective, multicenter validation is required before this model can be implemented as a routine clinical susceptibility testing tool. IMPORTANCE: The increasing prevalence of ceftriaxone-resistant nontyphoidal Salmonella in pediatric patients, particularly in cases requiring antimicrobial therapy, highlights the need for faster antimicrobial susceptibility testing. In this study, we developed a machine learning model integrated with MALDI-TOF MS to predict ceftriaxone resistance in NTS and deployed it as a web-based research-use interface. This proof-of-concept approach may support the future development of rapid adjunctive tools for antimicrobial resistance prediction.

Background: Acinetobacter baumannii and Klebsiella pneumoniae are important causes of hospital-acquired infections in pediatric patients, but comparative data on their clinical manifestations and inflammatory biomarkers remain limited. Methods: We retrospectively analyzed 55 children with single-positive blood cultures for A. baumannii (n = 20) or K. pneumoniae (n = 35), together with 30 healthy controls. Results: CRP, IL-6, and IL-10 were higher in infected children than in healthy controls. Logistic regression identified CRP and the IL-6/IL-10 ratio as exploratory correlates of infection. In ROC analyses distinguishing infected children from healthy controls, IL-6 showed the highest AUC, followed by IL-10 and CRP. In pathogen-level analyses, the IL-6/IL-10 ratio and lipase showed exploratory discriminatory signals. Conclusions: In this small retrospective case–control cohort, CRP, IL-6, and IL-10 were associated with microbiologically confirmed infection. Lipase may represent a potential biomarker for differentiating A. baumannii from K. pneumoniae infection, but its clinical utility requires prospective validation in larger multicenter cohorts using clinically relevant inpatient control groups.

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.

Invasive pneumococcal disease (IPD) poses a severe threat to children, with molecular epidemiological shifts driven by vaccination and antimicrobial pressu

Enterococci are major opportunistic pathogens causing healthcare-associated infections in children. Linezolid, a WHO-designated critically important antibiotic for multidrug-resistant Gram-positive infections, is increasingly challenged by linezolid-non-susceptible enterococci (LNSE). Yet pediatric LNSE epidemiology and genomics data remain scarce, hindering targeted control. We analyzed 26 LNSE strains isolated from Children’s Hospital, Zhejiang University School of Medicine (June 2020–July 2024) using MALDI-TOF MS, Vitek2 Compact, micro-broth dilution (for linezolid MIC), MLST, resistance/virulence gene detection, and pan-genome analysis (COG/KEGG annotation). Enterococcus faecalis (E. faecalis) dominated (23/26,88.5%) with ST16 as the major sequence type (ST) and four novel STs identified; all strains harbored optrA and fexA, with species-specific resistance/virulence gene profiles. The 23 E. faecalis strains exhibited an open pan-genome (b = 0.174725), indicating the possible existence of active horizontal gene transfer (HGT), with core, accessory, and unique genes showing distinct functional differentiation. These findings provide critical and robust empirical data to inform the development of targeted prevention and control strategies against LNSE in pediatric populations.

The emergence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) within healthcare settings is recognized as an “urgent threat

Eravacycline (ERV) has demonstrated promising in vitro antibacterial activity against carbapenem-resistant Klebsiella pneumoniae (CRKP). Nonetheless, its clinical application in pediatric cases remains underexplored. Therefore, we assessed the in vitro activities of ERV and tigecycline (TGC) against CRKP isolates obtained from pediatric patients in China between 2019 and 2024. The susceptibility rates of the 74 CRKP strains to TGC and ERV were 100% and 87.8%, respectively. Both TGC and ERV had MIC ranges of 0.125–2 μg/mL, with MIC ₅₀ at 0.25 µg/mL and MIC ₉₀ at 1 µg/mL. Statistically significant differences in ERV susceptibility were observed across different carbapenemases, sequence types (STs), and age groups, with the type of carbapenemase emerging as the primary determinant. The lowest susceptibility was noted for bla _KPC-2 (64.3%) and ST11 (54.6%), while bla _NDM-1 (97.4%), ST25, and ST17 (100%) exhibited the highest. The lowest susceptibility was observed in CRKP strains isolated from >3-year group (46.7%), whereas strains from both neonates and toddlers exhibited 100% susceptibility. When the MIC was below 0.5 µg/mL, ERV exhibited higher inhibition rates against CRKP compared to TGC. However, at MIC values of 0.5, 0.75, 1.5, and 2 µg/mL, the inhibition rates of both drugs were comparable. Among CRKP strains carrying bla _KPC-2 , bla _NDM-1 , and bla _NDM-5 , both the MIC ₅₀ and MIC ₉₀ values of ERV were less than or equal to TGC’s. ERV consistently had lower or equal MIC ₉₀ values compared to TGC for common STs, except for ST11, where ERV’s MIC ₅₀ was also lower or equal. ERV demonstrated significant in vitro activity against pediatric CRKP isolates collected over a 6-year period, supporting its potential benefits in treating pediatric CRKP infections, although further in vivo validation is necessary. IMPORTANCE: Eravacycline (ERV) has demonstrated promising in vitro antibacterial activity against carbapenem-resistant Klebsiella pneumoniae (CRKP). Current research predominantly addresses adult populations, leaving its clinical application in pediatric cases insufficiently explored. Given that the resistance mechanisms of CRKP in pediatric patients differ from those in adults, primarily due to the production of metallo-β-lactamases, and considering that ERV, like tigecycline, may be used off-label in pediatric populations, this study was conducted. The results demonstrate that ERV exhibited significant in vitro efficacy against pediatric CRKP isolates. However, unlike previous studies, the susceptibility rates of ERV vary considerably across different carbapenemases, sequence types, and age groups of CRKP, with the type of carbapenemase emerging as the primary determinant. These findings suggest that ERV has promising in vitro activity against CRKP isolates from pediatric patients, indicating potential clinical applicability for this demographic.

Mixed infection with influenza A virus (IAV) and Staphylococcus aureus (S. aureus) is a serious concern in children. S. aureus, particularly Panton-Valenti