Abstract
Legionella spp. predominantly Legionella pneumophila, are recognized respiratory pathogens, while soft tissue infections caused by non-pneumophila species remain exceptionally rare. We present the first documented case of L. maceachernii soft tissue infection in an infant worldwide. The patient presented with fever accompanied by occipital, anterior thoracic, and wrist masses. Diagnosis was confirmed through metagenomic next-generation sequencing (mNGS) of tissue samples with histopathological correlation. Initial empiric therapy with vancomycin and cefotaxime yielded no clinical improvement. Subsequent mNGS analysis of cerebrospinal fluid and lesional tissue identified L. maceachernii infection, prompting targeted antimicrobial therapy with levofloxacin and rifampicin that resulted in clinical resolution. A review of historical cases reveals that Legionella soft tissue infections typically occur in immunocompromised hosts or those receiving immunosuppressive therapies, and this association prompted an investigation into possible congenital immunodeficiency in our patient. Whole exome sequencing coupled with Sanger sequencing validation identified a pathogenic mutation in the IL2RG gene, confirming X-linked severe combined immunodeficiency (X-SCID) in the infant and carrier status in the mother. This case highlights three paradigm-shifting concepts in pediatric infectious disease management, including 1) L. maceachernii should be included in the differential diagnosis of pediatric soft tissue infections refractory to standard therapy, 2) underlying immunodeficiency must be systematically evaluated in pediatric patients with atypical Legionella infections, and 3) the diagnostic utility of mNGS in identifying fastidious pathogens and underscore the importance of genomic investigations in elucidating immunological comorbidities.