Beyond Conventional Diagnostics: When Only mNGS Can Support the Diagnosis in a Complex Immunocompromised Patient
Next-generation metagenomic sequencing (mNGS) allows direct and unbiased pathogen detection from clinical samples, overcoming the limitations of standard methods. It is particularly valuable for immunocompromised patients and complex infections. We describe the case of a 40-year-old man from North Africa admitted with progressive skin and soft-tissue lesions after a minor foot trauma. The initially localized infection rapidly worsened, leading to bilateral pneumonia, acute respiratory failure, disseminated intravascular coagulation, and death. Histopathological examination showed granulomatous inflammation with alcohol-resistant bacilli and revealed an undiagnosed cutaneous T-cell lymphoma associated with hemophagocytic syndrome. Conventional microbiological tests identified multiple pathogens, including Influenza A, HSV-1, Candida albicans, Enterococcus faecalis, Proteus mirabilis, and Pseudomonas aeruginosa, but their heterogeneous distribution and isolation from non-sterile sites hindered etiological interpretation. Cultures and molecular assays for Mycobacterium species were negative, despite suggestive histology. To clarify the diagnosis, mNGS was performed on blood, serum, and lymph node samples using host DNA depletion and Illumina sequencing. Bioinformatic analysis revealed a diverse microbial landscape, with the detection of Fusarium pseudograminearum, Mycobacterium canettii, Ralstonia insidiosa, Klebsiella pneumoniae, and Staphylococcus aureus, alongside low-level viral sequences (EBV, HSV-1). These results reflected the patient's severe immune deficiency, characterized by a marked depletion of CD8? T cells and NK cells. Although results became available too late to influence treatment, mNGS provided crucial diagnostic insights, demonstrating its ability to uncover hidden or rare pathogens. Early application of mNGS could significantly improve diagnostic precision and therapeutic decisions in critically ill immunocompromised patients.
Next-generation metagenomic sequencing (mNGS) allows direct and unbiased pathogen detection from clinical samples, overcoming the limitations of standard methods. It is particularly valuable for immunocompromised patients and complex infections. We describe the case of a 40-year-old man from North Africa admitted with progressive skin and soft-tissue lesions after a minor foot trauma. The initially localized infection rapidly worsened, leading to bilateral pneumonia, acute respiratory failure, disseminated intravascular coagulation, and death. Histopathological examination showed granulomatous inflammation with alcohol-resistant bacilli and revealed an undiagnosed cutaneous T-cell lymphoma associated with hemophagocytic syndrome. Conventional microbiological tests identified multiple pathogens, including Influenza A, HSV-1, Candida albicans, Enterococcus faecalis, Proteus mirabilis, and Pseudomonas aeruginosa, but their heterogeneous distribution and isolation from non-sterile sites hindered etiological interpretation. Cultures and molecular assays for Mycobacterium species were negative, despite suggestive histology. To clarify the diagnosis, mNGS was performed on blood, serum, and lymph node samples using host DNA depletion and Illumina sequencing. Bioinformatic analysis revealed a diverse microbial landscape, with the detection of Fusarium pseudograminearum, Mycobacterium canettii, Ralstonia insidiosa, Klebsiella pneumoniae, and Staphylococcus aureus, alongside low-level viral sequences (EBV, HSV-1). These results reflected the patient's severe immune deficiency, characterized by a marked depletion of CD8? T cells and NK cells. Although results became available too late to influence treatment, mNGS provided crucial diagnostic insights, demonstrating its ability to uncover hidden or rare pathogens. Early application of mNGS could significantly improve diagnostic precision and therapeutic decisions in critically ill immunocompromised patients.
Bambino Gesu Paediatric Hospital, Rome