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Although the International Society for Peritoneal Dialysis (ISPD) guidelines significantly improve the diagnostic rate by placing peritoneal dialysis fluid into blood culture bottles, peritonitis caused by atypical pathogens, such as tuberculosis and fungi, is difficult to diagnose due to challenges in culturing these organisms using traditional methods, leading to high mortality. Metagenomic next-generation sequencing (mNGS) technology has been widely used as an accurate diagnostic technique for infectious diseases. First used in identifying and quantifying environmental micro-organisms, mNGS technology can identify rare, novel, difficult-to-detect and mixed pathogens directly from clinical samples, and has potential in predicting antibiotic resistance. This paper summarizes the application of mNGS in atypical and rare pathogens peritonitis clinical cases in recent years, and provides reference for the diagnosis of peritonitis in combination with new ISPD guidelines and diagnostic techniques. The development and principles of mNGS technology, diagnostic efficiency in peritonitis, challenges in diagnosis of atypical and rare pathogen-associated peritonitis, and application of mNGS technology are discussed in detail. The development of mNGS technology provides clinicians with powerful tools to more accurately identify and treat peritonitis. Future research needs to focus on reducing costs, improving test accessibility, and developing new bioinformatics tools to better integrate mNGS results into clinical practice.<\/jats:p>","DOI":"10.1177\/08968608251333879","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T18:48:22Z","timestamp":1747680502000},"page":"315-324","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Diagnostic challenges in peritoneal dialysis-associated peritonitis with atypical and rare pathogens: A new era of metagenomic next-generation sequencing precision diagnosis"],"prefix":"10.1177","volume":"46","author":[{"given":"Xiao","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University; Key Laboratory of Nephrology, National Health Commission and Guangdong Province, Guangzhou, P.R. 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