Abstract: A 66-year-old male patient diagnosed with small-cell lung cancer received chemotherapy and immunotherapy, resulting in successful tumor control. However, the patient subsequently experienced a fever and rapid progression of the pulmonary cavity. Despite sampling bronchoscopic bronchoalveolar lavage fluid for targeted next-generation sequencing (tNGS), the cause remained unidentified. Adding bronchoalveolar lavage fluid to sense metagenomic next-generation sequencing (mNGS) confirmed the infection caused by actinomycetes. The patient’s condition improved after active anti-infection treatment. This case was further analyzed and discussed through a comprehensive literature review, focusing on molecular microbiological diagnosis and treatment processes. The points outlined were as follows: the advancement of molecular microbiology has gradually reduced the challenges associated with diagnosing rare infectious diseases such as pulmonary actinomycosis. Additionally, in immunodeficient individuals, certain infectious diseases with a chronic course may exhibit acute and aggressive characteristics, which is of concern to all colleagues. Currently, tNGS and mNGS are widely employed in clinical settings as practical tools for diagnosing infectious diseases. Notably, these two methods are not substitutes for each other but complement each other.

Keywords: pulmonary actinomycosis, lung cancer, targeted next-generation sequencing, metagenomic next-generation sequencing