Arthritis caused by Legionella micdadei and Staphylococcus aureus: metagenomic next-generation sequencing provides a rapid and accurate access to diagnosis and surveillance

Abstract

Legionella spp. is an important pulmonary pathogen but rarely causes extra-pulmonary infections.We report a case of joint infection caused by Legionella micdadei and Staphylococcus aureus in a 54-year-old male with medication history of oral steroid for systemic lupus erythematosus (SLE). He developed arthritis in his right metacarpophalangeal (MCP) joints without precursor pneumonia. In the joint aspirate, S. aureus was detected through culture. The existence of L. micdadei and S. aureus were indicated by metagenomic next-generation sequencing (mNGS) and confirmed by 16S rRNA sequence analysis. After oral levofloxacin treatment for 54 days, the patient's symptoms ameliorated and blood test results improved, which were consistent with the dynamic trend of reads numbers in mNGS data. Our case included, arthritis caused by Legionella spp. have been reported in 11 patients. However, our case is the first to report septic arthritis caused by L. micdadei in native joints and monitored by mNGS. This case demonstrated an application of mNGS for etiological diagnosis and semi-quantification in joint aspirate. mNGS may serve as a promising tool for rapid and accurate etiological diagnosis and surveillance, contributing to appropriate antimicrobial drug applications and timely medication adjustments when necessary.

The microbiological diagnostic performance of metagenomic next-generation sequencing in patients with sepsis

“…To our knowledge, this is the first report to identify the cut-off reads for diagnosing distinct pathogens, especially for patients with sepsis, which is indeed favorable for the clinical application of mNGS. In fact, mNGS has been used to isolate distinct microbes in various diseases, such as Streptococcus pneumoniae in pediatric bacterial meningitis, Ebola virus disease, and arthritis caused by Legionella micdadei as well as Staphylococcus aureus [ 15 , 17 , 18 ]. Although these reports show good performance in terms of pathogen detection, few provide optimal cut-off reads for each pathogen.…”

Current status of use of high throughput nucleotide sequencing in rheumatology

“…Other assays ( online supplemental figure S3 ) include the analysis of bacterial species using HTS (metagenomics, n=33; 5%) in, for example, a joint infection in a patient with SLE, 59 of the faecal microbiota of SLE mice 60 or the lung microbiota in early RA, 61 as well as epigenetic analysis (n=32, 5%) in SLE, 35 62 RA, 63 64 systemic sclerosis 65 and finally, phage immunoprecipitation sequencing (n=1) for HTS of autoantibody repertoires in systemic sclerosis. 66 …”

Disseminated Legionella micdadei infection in a liver transplant patient presenting as pulmonary nodules and a laryngeal lesion

“…5 Molecular diagnostics such as 16S rRNA PCR and metagenomic next-generation sequencing (mNGS) have significantly improved diagnosis of Legionella infection; in fact, 16S rRNA PCR has been shown to identify up to 87% of nonpneumophila Legionella species, 10 and mNGS was able to identify Legionella micdadei in a case of septic arthritis caused by concurrent Legionella micdadei and Staphylococcus aureus infection. 11 In our patient's case, 16S rRNA amplification performed on lung and laryngeal biopsy tissue identified Legionella micdadei.…”