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This study aimed to elucidate the epidemiological features and clinical implications of\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              infections in children and explore the potential influence of SARS-CoV-2 Omicron variants and influenza A infections on the\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              outbreak. Among 38,668 children with lower respiratory tract infections from January to December 2023, 11,919 tested positive for\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              , predominantly between October and December. The majority of the children with\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              were aged 5\u201310 years, with type 1 strains and macrolide-resistant\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              strains having the highest prevalence rates. Statistical analysis revealed elevated C-reactive protein, neutrophil, and monocyte levels and decreased lymphocyte, basophil, and eosinophil counts in\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              -positive children.\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              -positive children also presented significantly increased neutralizing antibody levels against preceding influenza A (H3N2) but not against SARS-CoV-2 Omicron variants. A parallel trend was observed between\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              and H3N2 prevalence from June to December 2023. The emergence of macrolide-resistant strains and prior influenza A (H3N2) epidemics notably contributed to the\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              outbreak. These findings suggested that H3N2 infection facilitates\n              <jats:italic>M. pneumoniae<\/jats:italic>\n              infection through various mechanisms. This study underscores the complex interactions between respiratory pathogens and highlights the need for comprehensive surveillance and response strategies.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                This study identified key factors contributing to an outbreak of\n                <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                that affected 11,919 children. The influencing factors included a high prevalence of macrolide-resistant epidemic strains (94.2%) and significantly higher H3N2 neutralizing antibody levels (\n                <jats:italic>P<\/jats:italic>\n                &lt; 0.0001) stimulated by the preceding H3N2 influenza epidemic. These findings highlight the complex relationship between the prevalence of\n                <jats:italic>M. pneumoniae<\/jats:italic>\n                and H3N2 infection in children, indicating that it is necessary to consider pathogen interactions in respiratory disease management by continuously monitoring respiratory pathogens. The emergence of macrolide-resistant strains in China and the previous H3N2 influenza epidemic significantly exacerbated the severity of the\n                <jats:italic>M. pneumoniae<\/jats:italic>\n                outbreak. H3N2 infection potentially amplifies Mycoplasma transmission. This study elucidates the epidemiological and clinical aspects of\n                <jats:italic>M. pneumoniae<\/jats:italic>\n                infections in children, yields insights regarding the cause of the outbreak, and provides guidance for improving respiratory infection management.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01844-24","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T14:40:17Z","timestamp":1740494417000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic impact of macrolide resistance and H3N2 infection on\n            <i>M. pneumoniae<\/i>\n            outbreak in children"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0955-7897","authenticated-orcid":false,"given":"Jiali","family":"Chen","sequence":"first","affiliation":[{"name":"Key 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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunping","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Fudan University","place":["Shanghai, China"]},{"name":"Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuezhou","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of 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