COVID-19 Pandemic Increased ESKAPEEc Bloodstream Infections and Amplified Carbapenem Resistance in Chinese Children: a Multicentre Surveillance Study (2016–2023)

Li Xiaoqiang¹Xu Hongmei¹Wang Cai¹Ruiqiu Zhao¹Wu Jiaying¹Yu Hui²Chuanqing Wang²Pan Fu²Jikui Deng³Chunzhen Hua⁴Yinghu Chen⁴Mingming Zhou⁴Ting Zhang⁵Zhang Hong⁵Chen Yiping Chen⁶Shifu Wang⁷Qing Cao⁵Huiling Deng⁸Cai Huijun⁸Hao Jianhua⁹Zhou Yuyang⁹Jing Chunmei^1,10*

• ¹Children‘s Hospital of Chongqing Medical University, Chongqing, China
• ²Children's Hospital of Fudan University National Children's Medical Center, Shanghai, China
• ³Shenzhen Children's Hospital, Shenzhen, China
• ⁴Zhejiang University School of Medicine Children's Hospital, Hangzhou, China
• ⁵Children's Hospital of Shanghai, Shanghai, China
• ⁶The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
• ⁷Children's Hospital Affiliated to Shandong University, Jinan, China
• ⁸Xi'an Jiaotong University Affiliated Children's Hospital, Xi'an, China
• ⁹Children's Hospital of Kaifeng, Kaifeng, China
• ¹⁰Chongqing University, Chongqing, China

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. 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 of ESKAPEEc pathogens significantly decreased for the coronavirus disease 2019 (COVID-19) infection periods compared to the pre-pandemic period. 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. 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. 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. 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. 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.