Persistent CD4+ lymphopenia is associated with recurrent Nocardia farcinica infection and acquired resistance in an AIDS patient: a case report with immunological warning.

After severe depletion of CD4 T cells in AIDS patients, they are not only prone to a first-time Nocardia infection, but also, even if cured, unable to form protective immune memory, leaving them susceptible to reinfection with the same pathogen. More seriously, in the absence of immune surveillance, irregular drug use can accelerate the selection of drug-resistant strains. A 32-year-old man with AIDS and persistent CD4+ count below 100 cells/μL for over three years (nadir 2 cells/μL) developed right lower lobe pneumonia caused by Nocardia farcinica four years before the current admission, which was cured with a TMP-SMX-containing regimen. The isolate was sensitive to trimethoprim-sulfamethoxazole (TMP-SMX), and the lesion nearly resolved after treatment. He was prescribed long-term TMP-SMX prophylaxis at discharge but stopped taking it on his own. One year before the current admission, he received sulfadiazine plus pyrimethamine for clinically diagnosed cerebral toxoplasmosis, but his adherence was poor and irregular. On current admission (day 1), he was readmitted with high fever and sepsis. Chest CT showed multiple cavities in the left lower lobe. Blood cultures flagged positive at 25 hours and were identified as Nocardia farcinica. The microbiologist reviewed his old records, found the previous nocardial history, and recommended bronchoalveolar lavage (BAL). BAL metagenomic next-generation sequencing again identified Nocardia farcinica, but susceptibility testing now showed resistance to TMP-SMX (MIC ≥8/152). He improved after switching to imipenem plus amikacin. He received intravenous imipenem plus amikacin for 14 days, followed by oral linezolid for 6 weeks. At the last follow-up (approximately one year after discharge), his CD4+ had risen to only 11 cells/μL, and he had no further nocardial infection. This case shows that when CD4+ stays below 100 for a long time, even a first nocardial infection can be cured but may leave insufficient immune memory, rendering the patient susceptible to subsequent infection. The distinction between true reinfection and late relapse could not be definitively established in the absence of strain-level homology data. Irregular, sub-therapeutic sulfonamide exposure, combined with a non-functional immune system, can select for resistant strains.