AbstractIntroductionConventional etiological detection and pathogenic antibody methods make it challenging to identify the atypical pathogens among the community‐acquired pneumonia (CAP). Metagenomic next‐generation sequencing (mNGS) could rapidly detect all potentially infectious diseases and identifies novel or potential pathogens.MethodsEighteen patients diagnosed with atypical CAP were enrolled in this retrospective study, including nineChlamydia psittacipneumonia(C. p), fourLegionella pneumonia(L. p) and fiveMycoplasma pneumonia(M. p). We simultaneously tested bronchoalveolar lavage fluid (BALF) samples for conventional microbiological methods and mNGS, and blood specimens were analysed. We also collected and compared baseline and clinical characteristics and treatment responses.ResultsPatients withC. pandL. phad similar symptoms, including fever, cough, headache, dyspnoea, asthenia, shivering and headache, compared withM. p, whose symptoms were slight.C. pandL. pusually showed multiple lobar distributions with pleural effusion. Serologic testing indicated thatL. phad higher levels of white blood cells (WBCs), neutrophils, C‐reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine compared withM. pandL. p(p< 0.05). However, patients withC. phad lower levels of albumin (p< 0.05), andM. phad a minimum risk of cardiac volume loads (p< 0.05). CD4/CD8 ratio, lymphocytes, aspartate aminotransferase (AST), creatine kinase (CK), cell counting of BALF and coagulation had no difference (p< 0.05). Pathogenic IgM assay showed that 4/5 cases were positive forM. pand no positive detection forC. pandL. pinfection. We timely adjusted the antibiotics according to the final mNGS results. Eventually, 16/18 patients recovered fully. Conditions ofL. ppatients were worse than those ofC. ppatients, and those ofM. ppatients were the least.ConclusionEarly application of mNGS detection increased the atypical pathogenic identification, improved the prognosis and made up for the deficiency of conventional detection methods.